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AIDS-
Acquired Immunodeficiency Syndrome
Presented by-
Dr.Payal Dash
1st year Pg Trainee
1
CONTENTS
• Introduction
• Background
• HIV Virus
• Etiopathogenesis
• AIDS
• Epidemiology -globally & India
• Risk Factors
• Modes of transmission
• Oral Manifestations of HIV
PART 1
2
INTRODUCTION
• What is HIV?
• Who is an HIV positive person?
• Persons who are HIV-positive are both
infected and infectious for life.
• Disease-Resulting from a pathophysiological
response to external or internal factors. (Macilwaine SW. What is a Disease?. Br Med J. 1900;2(2085):1703–1704. )
• Disorder-A disruption of the disease to the
normal or regular functions in the body or a part of the body.
• Syndrome-A collection or set of signs and symptoms that characterise or suggest a
particular disease.Calvo F, Karras BT, Phillips R, Kimball AM, Wolf F. Diagnoses, syndromes, and diseases: a knowledge representation problem.
AMIA Annu Symp Proc. 2003;2003:802.
3
BACKGROUND
• HIV originated in Kinshasa, in the Democratic Republic of Congo around 1920
when HIV crossed species from chimpanzees to humans.
• 1981- Pneumocystis carinii pneumonia (PCP) were found in five young, previously
healthy gay men in Los Angeles. At the same time, there were reports of a group of
men in New York and California with Kaposi’s Sarcoma
• 1982-In September, the CDC used the term 'AIDS' (acquired immune deficiency
syndrome) for the first time, describing it as
• a disease at least moderately predictive of a defect in cell mediated immunity,
occurring in a person with no known case for diminished resistance to that disease
• 1983-In January 1983, AIDS was reported among the female partners of men who
had the disease suggesting it could be passed on via heterosexual sex.
• By the end of the year the number of AIDS cases in the USA had risen to 3,064 - of
this number, 1,292 had died.
4
• 1984-In April 1984, the National Cancer Institute announced they had found the
cause of AIDS, the retrovirus HTLV-III.
• 1985-In March 1985, the U.S Food and Drug Administration (FDA) licensed the first
commercial blood test, ELISA, to detect antibodies to the virus. Blood banks began
to screen the USA blood supply
• 1986-May 1986, the International Committee on the Taxonomy of Viruses said that
the virus that causes AIDS will officially be called HIV (human immunodeficiency
virus) instead of HTLV-III/LAV.
• 1987-In February 1987, the WHO launched The Global Program on AIDS to raise
awareness; generate evidence-based policies
• In March, the FDA approved the first antiretroviral drug, zidovudine (AZT), as
treatment for HIV.
• 1988- WHO declared 1st December as the first World AIDS Day.
• 1989-In March 1989, 145 countries had reported 142,000 AIDS cases.USA-100000
5
6
1990 On 8 April 1990, Ryan White died of an AIDS-related illness aged 18
October, the FDA approved the use of zidovudine (AZT)
to treat children with AIDS
1991 the Visual AIDS Artists Caucus launched the Red Ribbon Project to create a symbol of
compassion for people living with HIV and their carers. The red ribbon became an
international symbol of AIDS awareness.
On 7 November, professional basketball player Earvin (Magic)
Johnson announced he had HIV and retired from the sport
A couple of weeks later, Freddie Mercury, lead singer of rock group Queen, announced he
had AIDS and died a day later.
1992 Tennis star Arthur Ashe revealed he became infected with HIV as the result of a blood
transfusion in 1983.
In May, the FDA licensed a 10 minute testing kit which could be used by healthcare
professionals to detect HIV-1
7
1993 an estimated 2.5 million AIDS cases globally
1994 In August 1994, the USA Public Health Service recommended the use of AZT to prevent the mother-
to-child transmission of HIV.
In December, the FDA approved an oral HIV test - the first non-blood HIV test.
1995 In June 1995, the FDA approved the first protease inhibitor beginning a new era of highly active
antiretroviral treatment (HAART).
immediate decline of between 60% and 80% in rates of AIDS-related deaths and hospitalisation in
those countries which could afford it.
4.7 million new HIV infections - 2.5 million in southeast Asia and 1.9 million in sub-Saharan Africa.
1997 UNAIDS estimated that 30 million people had HIV worldwide equating to 16,000 new infections a
day
1999 the WHO announced that AIDS was the fourth biggest cause of death worldwide and number one
killer in Africa. An estimated 33 million people were living with HIV and 14 million people had died
from AIDS since the start of the epidemic
8
2000 In September, the United Nations adopted the Millennium Development Goals which included a specific
goal to reverse the spread of HIV, malaria and TB.
2001 In November, the World Trade Organization (WTO) announced the Doha Declaration which allowed
developing countries to manufacture generic medications to combat public health crises like HIV.
2002 In November, the FDA approved the first rapid HIV test with 99.6% accuracy and a result in 20 minutes
2013 In 2013, UNAIDS reported that AIDS-related deaths had fallen 30% since their peak in 2005.91
An estimated 35 million people were living with HIV.
2017 For the first time ever, more than half of the global population living with HIV are receiving antiretroviral
treatment, a record of 19.5 million people.
• 2018-
• Globally, 37.9 million people living
with HIV
• 23.3 million people were receiving
antiretroviral treatment
• 2019-
• In June 2019, 24.5 million people were
accessing antiretroviral therapy.
• Between 2000 and 2018, new HIV
infections fell by 37% and HIV-related
deaths fell by 45%, with 13.6 million
lives saved due to ART.
9
HIV VIRUS
• Human immunodeficency virus-double stranded RNA virus
• Phylum: incertae sedis
• Family: Retroviridae
• Genus: Lentivirus
• Class: incertae sedis
• Order: Ortervirales
• Subfamily: Orthoretrovirinae
• Types of HIV -HIV 1 , HIV 2
10
SPECIES VIRULENCE INFECTIVITY Prevalence
HIV 1 High High Global
HIV 2 Low Low West Africa
Types and Subtypes of HIV
11
HIV
HIV 1
Group M
A-L
Group N Group O Group P
HIV 2
Group
A-H
• HIV 1
• most common and pathogenic strain of the virus
• major group (Group M) namely Group N, O and a group P.
• With 'M' for "major", this is by far the most common type of HIV, with more than
90% of HIV/AIDS cases deriving from group M
• M group is subdivided further into clades, called subtypes from A-L
12
• Subtype A - eastern Africa.
• Subtype B -Europe, the Americas, Japan, and Australia
• Subtype C - Southern Africa, Eastern Africa, India, Nepal, and parts of China.
• Subtype D - Eastern and central Africa
• Subtype E - Southeast Asia
• Subtype F - in central Africa, South America and Eastern Europe
• Subtype G - in Africa and central Europe.
• Subtype H - central Africa
• Subtype J is primarily found in North, Central and West Africa, and the Caribbean
• Subtype K and L is limited to the Democratic Republic of Congo (DRC) and
Cameroon.
13
• Group N
• The 'N' stands for "non-M, non-O".
• This group was discovered by a Franco-Cameroonia team in 1998 .
• As of 2015, less than 20 Group N infections have been recorded.
• Group O
• The O ("Outlier") group has infected about 100,000 individuals located in West-
Central Africa
• Most common in Cameroon, 2% of HIV-positive samples were from Group O.
14
• Group P
• In 2009, a newly analyzed HIV sequence was reported to have greater similarity to a
simian immunodeficiency virus recently discovered in wild gorillas
• The virus had been isolated from a Cameroonian woman residing in France who was
diagnosed with HIV-1 infection in 2004.
15
• HIV 2
• The first case in the United States was in 1987.
• As of 2010, there are 8 known HIV-2 groups (A to H).
• Of these, only groups A and B are pandemic.
• Group A is found mainly in West Africa, but has also spread globally to Angola,
Mozambique, Brazil, India, Europe, and the US.
• Group B is mainly confined to West Africa
• HIV-2 is closely related to simian immunodeficiency virus endemic in sooty
mangabeys (Cercocebus atys atys) (SIVsmm), a monkey species inhabiting the
forests of Littoral West Africa.
16
HIV STRUCTURE
Lipid envelope
receptor complex
structural proteins
enzymes
RNA
17
HIV STRUCTURE
• spherical, 100 (90-120) nm in diameter.
• lipid envelope, in which are embedded the
trimeric transmembrane glycoprotein gp41
to which the surface glycoprotein gp120 is
attached
• matrix protein p17,
• core proteins p24 and p6
• nucleocapsid protein p7
• lies 2 copies of the ~10 kilobase (kb)
positive-sense, viral RNA genome (i.e. it has
a diploid RNA genome),
• protease, integrase and reverse transcriptase
enzymes. 18
HIV STRUCTURE
• Viral Genes and antigens
• 9 genes to code for the necessary
proteins and enzymes.
• principal genes are gag, pol, and
env.
• gag gene - core proteins.
• pol gene- enzymes
• env gene - glycoproteins.
• rev, nef, vif, vpu, vpr, and tat—are
important for viral replication and
enhancing HIV’s infectivity rate.
19
• Genes coding for structural proteins
• participate in functional structure of virus
• 1.gag gene(group specific antigen)
• encodes for core and shell of virus
• gene product is precursor protein p55 ,cleaved into p17(matrix protein),p24,p15
• The p24 (CA-capsid )protein forms the conical core of viral particles
• p24 antigen(major core protein) can be detected in early stages in serum till the
appearance of the antibodies
20
• 2.pol gene
• encodes reverse transcriptase ,protease and integrase
• Pol has RNA-dependent and DNA-dependent polymerase activities.
• expressed as precursor protein cleaved into p64,p51,p10,p32
• p64-reverse transcriptase and RNAse activity
• p51-only reverse transcriptase activity
• p10-protease,p32-integrase
• RT is required to transcribe DNA from RNA template, and IN is necessary to
integrate the double-stranded viral DNA into the host genome.
21
• env gene(envelop)
• determines synthesis of envelop gp160 that is cleaved into gp120 and gp41
• cleaved by a host protease, furin, within the endoplasmic reticulum of the host cell.
• The post-translational processing produces a surface glycoprotein, gp120 , which
attaches to the CD4 receptors present on lymphocytes, and gp41, which embeds in
the viral envelope to enable the virus to attach to and fuse with target cells
22
Essential regulatory proteins
• tat (HIV trans-activator)
• regulates the reverse transcription of viral genome RNA, ensuring efficient
synthesis of viral mRNAs and regulating the release of virions from infected cells.
• rev (regulator of expression of virion proteins):
• The Rev protein binds to the viral genome via an arginine-rich RNA-binding motif
that also acts as a NLS (nuclear localization signals), required for the transport of
Rev to the nucleus from cytosol during viral replication.
• Rev recognizes a complex stem-loop structure of the mRNA env located in the
intron separating coding exon of Tat and Rev, known as the HIV Rev response
element (RRE)
23
Non structural and regulatory proteins
• vif (viral infectivity factor gene)
• important for the infectivity of HIV-1 virions depending on the cell type. HIV-1 has
been found to require Vif to synthesize infectious viruses in lymphocytes,
macrophages, and certain human cell lines.
• vpr
• important role in replication of the virus, specifically, nuclear import of the
preintegration complex.
• also arrest host cell cycle in the G2 phase. This arrest activates the host DNA repair
machinery which may enable integration of the viral DNA.
• HIV-2 encode an additional Vpr related protein called Vpx which functions in
association with Vpr.
• vpu (Virus protein U) -
• specific to HIV-1
• involved in CD4 degradation 24
Structure of RNA genome HIV 1
25
ETIOPATHOGENESIS OF HIV
• Immune system and central nervous system
binding of virion
to surface of target
cell
interaction with
CXCR4 or CCR5
Membrane fusion
and cellular entry
involving gp41
Viral RNA reverse
transcribed to ds
DNA
DNA transcribed
to nucleus
DNA used to
transcribe new
RNA
26
ETIOPATHOGENESIS OF HIV
• Enabled by 3 viral genes-GAG,POL ,ENV
• 6 regulatory genes- VIF,VPR,VPU,NEF,TAT,REV
• half life -1-2 hours in plasma,1.5 days in infected CD4 cells, 12 months in latently
infected CD4 cells
viral mRNA
translated to viral
peptide chains
precursor
polyproteins form
new proteins and
enzymes (viral
protease)
migrate to cell
surface,
cell lysis occurs.
27
28
AIDS
• Acquired immunodeficiency syndrome ( "slim disease")
• caused by a retrovirus known as the human immunodeficiency virus (HIV) which
breaks down the body's immune system
• HIV 1(central africa) and HIV 2(west africa and india) known to cause AIDS
• diagnosed when CD4 cell count falls below 200 cells/mm3
• immune system ceases and results in advanced HIV (<50cells/mm3)
• When HIV infects a cell, it combines with that cell's genetic material and may lie
inactive for years. Most people infected with HIV are still healthy and can live for
years with no symptoms or only minor illnesses. They are infected with HIV, but they
do not have AIDS.
• without ART progression of HIV to death is 10-12 years
29
CLINICAL FEATURES
• The clinical features of HIV infection have been classified into four broad categories
:
• I. Initial infection with the virus and development of antibodies
• II. Asymptomatic carrier state
• Ill. AIDS-related complex (ARC)
• IV. AIDS.
30
• (I) INITIAL INFECTION
• mild illness (fever. sore throat and rash) about 70 per cent of people
• most HIV -infected people have no symptoms for the first five years
• Once infected, people are infected for life.
• HIV antibodies usually take between 2 to 12 weeks to appear in the blood-stream
• The period before antibodies are produced is the "window period" during which,
although the person is particularly infectious because of the high concentration of
virus in the blood, he will test negative on the standard antibody blood test.
• (II) ASYMPTOMATIC CARRIER STATE
• Infected people have antibodies, but no overt signs of disease, except persistent
generalized lymphadenopathy.
31
• (III)AIDS RELATED COMPLEX
• damage to the immune system, but no opportunistic infections
• they may exhibit one or more of the following clinical signs; unexplained diarrhoea
lasting longer than a month, fatigue , malaise, loss of more than 10 per cent body
weight, fever, night sweats, or other milder opportunistic infections such as oral
thrush,generalized lymphadenopathy or enlarged spleen.
• Patients from high-risk groups who have two or more of these manifestations
(typically including generalised lymphadenopathy), and who have a decreased
number of T -helper lymphocytes are considered to have AIDS-related complex
32
• (IV) AIDS
• End- stage of HIV infection
• Tuberculosis and Kaposi sarcoma
• fungal infections such as Candida oesophagitis, Cryptococcus meningitis
• parasitic infections such as Pneumocystis carinni pneumoni,or Toxoplasma gondii
encephalitis when T-helper cell count has dropped to around 100.
• cytomegaloviral retinitis
• "slim disease".
• AIDS encephalopathy or AIDS dementia
33
• Signs and symptoms-Fever,fatigue, maculopapular rash,headache,weight loss,
depression,night sweats,oral or genital ulcers
• Acute infection -few days -more than 10 weeks
1993 revised classification system for hiv infection and expanded AIDS
Survillience case definition for adoloscents and adults
34
WORLD AIDS DAY
• World AIDS Day takes place on 1 December each year.
• It’s an opportunity for people worldwide to unite in the fight against HIV, to show
support for people living with HIV, and to commemorate those who have died from
an AIDS-related illness.
• Founded in 1988, World AIDS Day was the first ever global health day.
• THE RED RIBBON
• universal symbol of awareness and support
for people living with HIV.
35
EPIDEMIOLOGY
• The spread of HIV started at the beginning of the 20th century.
• Zoonotic transmission of SIVcpz from chimpanzees (Pan troglodytes troglodytes) occurred for HIV-1
group M and group O around 1920 and for HIV-1 group N around 1960 in West Central Africa.
• HIV-2 was transmitted zoonotically from sooty mangabey (Cercocebus atys) to human in West Africa
around 1940.
• Since the mid-1980s the different HIV-1 M subtypes have been spreading, leading to a global
pandemic. In contrast to HIV-1, HIV-2 initially remained restricted to West Africa because of its
significantly lower infectivity.
• 35 million people were living with HIV in 2013
• The countries most affected by HIV with a high prevalence among 15- to 49-year-olds are Swaziland
(approximately 27%), Lesotho (approximately 23%) and Botswana (approximately 23%).
36
EPIDEMIOLOGY
• Germany
• From 2000 to around 2005 a significant increase of HIV infections was observed,
with a plateau since 2006
• most affected group were MSM with about 75% (2,400/3,200) of the total number of
new HIV infections in 2013.
• The total number of 3,200 (95% CI 3,000–3,400) new infections was estimated for
2013 showing differences in the number of infections in different groups affected
• The most affected group were men who have sex with men (MSM) with about 75%
(2,400/3,200) of the total number of new HIV infections in 2013. Approximately 360
women (11.3%) and 190 men (5.9%) contracted an HIV infection by heterosexual
contacts in Germany (hetero-domestic).
37
• Europe
• In 2012, approximately 30,000 new HIV diagnoses have been reported by 30
countries of the European Union (EU) and the European Economic Area (EEA)
• Most diagnoses were reported in Lithuania, Estonia, Belgium, the UK and
Luxembourg
• In 2012, the ratio of men to women in the group of new infections was 3.2:1.
• Since 2006 the percentage of newly diagnosed cases has been rather stable. However,
infections for which the information ‘sexual contacts between men’ was provided
have been increasing since 2006 by 11% to now 40.4%. The percentage of IVD with
a newly diagnosed HIV infection has been decreasing over the same period by 7%.
38
• Africa
• Africa is the continent that is affected most by HIV infections.
• About 25 million people in Africa live with HIV, about 22 million of whom in Sub-
Saharan Africa .
• The estimated HIV prevalence in Africa varies widely and lies between 0.1% in
Egypt and Morocco and about 27% in Swaziland.
• Heterosexual contacts are the main route of infection in Africa, and sex work and
sexual violence contribute significantly to the spread of the disease. Approximately
one third of those infected with HIV received antiretroviral therapy in 2013
• HIV prevalence in rural areas of Central Africa can be as low as a few ‰ and in
urban areas can reach values of up to 30% .
• HIV-1 M:C is the most prevalent subtype worldwide with a percentage of 30–36% of
all subtypes
39
• Australia
• In Australia, the number of new HIV diagnoses has been increasing by approximately
26% since 2003 and has reached a value of 5.4/100,000 inhabitants in 2012.
• The main mode of transmission is sexual contact among men .
• In Australia, the most common subtype is HIV-1 M:B; several additional subtypes
were imported mainly from Asia.
• North America
• About 50,000 new HIV diagnoses are reported annually in the USA with an
estimated prevalence of 0.23% .
• Approximately 1.1 million people live with HIV in the USA, 25% of whom are
women. The main route of transmission is sexual contact between men.
• About one third of all persons infected with HIV receive antiretroviral therapy
40
• South America
• In Latin America, approximately 1.3–1.9 million people are living with HIV. In
Belize, Guyana and Suriname, the estimated HIV prevalence is above 1% .
• Further recombinants are found in Brazil and in neighbouring countries
• Two other recombinant strains of the subtypes B and F are circulating in Argentina
41
• Asia
• In Asia, about 1.7 million people are living with HIV, approximately 50% of whom
receive antiretroviral therapy.
• The number of newly diagnosed HIV infections has decreased from 2001 to 2012
• by about 26%.
• With a generally low HIV prevalence in this region,Cambodia, China and India are
the countries with the highest proportion of new HIV diagnoses.
• The epidemic is concentrated in distinct groups with a high risk of exposure, such as
MSM, sex workers, drug users and transsexuals .
• In Asia, HIV prevalence reflects the contacts with Africa and North America.
42
43
44
45
Prevalence of HIV in INDIA
• National adult (15–49 years) HIV prevalence in India is estimated at 0.22%
(0.16% – 0.30%) in 2017.
• In 2017, adult HIV prevalence is estimated at 0.25%(0.18-0.34) among males and at
0.19% (0.14-0.25) among Females.
• The adult HIV prevalence at national level has continued its steady decline from an
estimated peak of 0.38% in 2001-03 through 0.34% in 2007, 0.28% in 2012 and
0.26% in 2015 to 0.22% in 2017.
• Mizoram has shown the highest estimated adult HIV prevalence of 2.04%(1.57-
2.56), followed by Manipur (1.43%, 1.17-1.75), Nagaland (1.15%, 0.92-1.41),
Telangana (0.70%, 0.50-0.95) and Andhra Pradesh (0.63%, 0.47-0.85).
(India HIV Estimation 2017 report)
46
• India is estimated to have had 22.67(10.92-40.60) thousand HIV positive women
who gave birth in 2017.
• State wise Prevention to Mother to child transmission (PMTCT) need were highest in
Maharashtra (2.41 thousand) followed by Uttar Pradesh (2.29 thousands), Bihar,
Andhra Pradesh, Karnataka, Telangana, West Bengal, Gujrat and Tamilnadu while
least were Sikkim.
• Since 2005, when the number of AIDS related deaths (ARD) started to show a
declining trend, the annual number of AIDS related deaths has declined by almost
71%. In 2017 an estimated 69.11 (29.94 –140.84) thousand people died of AIDS-
related causes nationally.
• AIDS-related deaths have dropped in all of India’s States/UT with the exception of
Assam, Bihar, Jharkhand, Haryana, Delhi, and Uttarakhand.
47
• India- 3rd largest HIV epidemic
• 88000 new HIV infections
• 69000 AIDS- related death
• 79 % aware of their status ,56% received antiretroviral treatment
48
RISK FACTORS
• Behaviours and conditions that put individuals at greater risk of contracting HIV
include:
• having unprotected anal or vaginal sex;
• having another sexually transmitted infection (STI)
• sharing contaminated needles, syringes and other injecting equipment and drug
solutions when injecting drugs;
• receiving unsafe injections, blood transfusions and tissue transplantation, and
medical procedures that involve unsterile cutting or piercing; and
• experiencing accidental needle stick injuries, including among health workers
49
• Key population affected in INDIA -
• Sex workers -
• 2017, 1.6% female sex workers had HIV
• Prevalence-7.4 % in Maharastra ,6.3 % in Andhra Pradesh
• 91% reported they used condom
• People who inject drugs
• majorly in north eastern states 12.1 % in Manipur, 10% in Mizoram
• Transgender people--
• 3.1%(2nd highest)
• NACO reported 45% received interventions
• Migrant workers-7.2 million migrant worker -0.2 % HIV
• Truck drivers-0.2 % lived with HIV
50
MODES OF TRANSMISSION
• (a) Sexual transmission (man to man,heterosexual and oral)
• (b) Parenteral(blood or blood product recipients,injection drug users,occupational
injury)
• (c) Vertical -Maternal- foetal transmission : mother-to child transmission
• Exposure rate-90% for blood and blood products
• 15-40%- vertical route
• 0.5-1 %-injection drug use
• 0.2-0.5%- genital mucus membrane spread
• 0.1%-non genital mucus membrane spread
• worldwide major route of transmission >75% is heterosexual
• 5-10 percent -children during pregnancy birth or breastfeeding
51
• SEXUAL CONTACT
• AIDS is first and foremost a sexually transmitted disease.
• Any vaginal, anal or oral sex can spread AIDS. Every single act of unprotected
intercourse with an HIV- infected person exposes the uninfected partner to the risk of
infection.
• The size of the risk is affected by a number of factors, including the presence of STD,
the sex and age of the uninfected partner, the type of sexual act, the stage of illness of
the infected partner, and the virulence of the HIV strain involved.
• women are more vulnerable to HIV infection .
• Anal intercourse carries a higher risk of transmission than vaginal intercourse
• For vaginal sex the risk is greater when woman is menstruating.
• Exposed adolescent girls and women above 45 years of age are more prone to get
HIV infection.
• In teenagers the cervix is thought to be less efficient barrier to HIV than in mature
genital tract of adult women.
52
• An STD in either the HIV- negative or the HIV-positive partner facilitates the
transmission of HIV.
• The risk of transmission is 8-10 times higher.
• As for HIV-infected people, they are more infectious to others in the very early
stages, before antibody production i.e. during the "window period'', and when the
infection is well advanced, because levels of virus in the blood at that time is higher
than at other times.
53
• Blood contact
• AIDS is also transmitted by contaminated blood -transfusion of whole blood cells,
platelets and factors VIII and IX derived from human plasma.
• The risk of contracting HIV infection from transfusion of a unit of infected blood is
estimated to be over 95 per cent.
• Since the likelihood of HIV transmission through blood depends on the "dose" of
virus injected, the risk of getting infected through a contaminated needle, syringe or
any other skin- piercing instrument is very much lower than with transfusion.
• needle- sharing by drug users is a major cause of AIDS in many countries, both
developed and developing, and in some it is the predominant cause.
• Any skin piercing (including injections, ear-piercing, tattooing, accupuncture or
scarification) can transmit the virus, if the instruments used have not been sterilized
and have previously been used on an infected person.
54
• Maternal- foetal transmission : mother-to child transmission
• HIV may pass from an infected mother to her foetus, through the placenta or to her
infant during delivery or by breast-feeding. In the absence of any intervention, rates of
this form of transmission can vary from 20- 25 per cent.
• Transmission during the peripartum period accounts for one third to two-thirds of
overall numbers infected
• The risk of infection is higher if the mother is newly infected, or if she has already
developed AIDS. HIV infected infants and children progress rapidly to AIDS.
55
How HIV is not transmitted
• shaking hands, hugging or kissing
• coughing or sneezing
• using a public phone
• visiting a hospital
• opening a door
• sharing food, eating or drinking
utensils
• using drinking fountains
• using toilets or showers
• using public swimming pools
• getting a mosquito or insect bite.
56
Oral Manifestations of HIV
• Oral manifestations of HIV infection occur in 30–80% of the affected patient
population.
• The various oral manifestations can be categorized into
• Infections: bacterial, fungal, viral
• Neoplasms: Kaposi's sarcoma, non-Hodgkin's lymphoma
• Immune mediated: major aphthous, necrotizing stomatitis
• Others: parotid diseases, nutritional, xerostomia
• Oral manifestations as adverse effects of antiretroviral therapy.
57
FUNGAL INFECTIONS
• Candidiasis:
• Oral or pharyngeal candidiasis are the commonest fungal infections observed as
the initial manifestation of symptomatic HIV infection.
• Many patients can have esophageal candidiasis as well.
• It is usually observed at CD4 counts of less than 300/μl.
• Candida albicans although nonalbicans species
have also been reported.
• erythematous candidiasis, pseudomembranous candidiasis,
angular cheilitis, and hyperplastic or chronic candidiasis:
58
• Erythematous candidiasis
• presents as a red, flat, subtle lesion either
• on the dorsal surface of the tongue and/or
the hard/soft palates.
• Patients complain of a burning sensation in the mouth
more so while eating salty and spicy food.
• Diagnosis is made on the basis of clinical examination, a potassium hydroxide
preparation which demonstrates the fungal hyphae can be used for confirmation.
• Pseudomembranous candidiasis
• appears as creamy white curd-like plaques on the
buccal mucosa, tongue, and other oral mucosal surfaces
that can be wiped away, leaving a red or bleeding surface
• extend to involve the oropharyx and esophagus
59
• Angular cheilitis is erythema and/or fissuring and cracks of the corners of the mouth.
Angular cheilitis can occur with or without the presence of erythematous candidiasis
or pseudomembranous candidiasis.
• Hyperplastic or chronic candidiasis presents as white nonremovable plaques over the
mucosal surface; hence they cannot be scraped off.
60
• Treatment of oral candidiasis depends on the clinical type, distribution, and severity
of infection.
• TOPICAL TREATMENT
• Clotrimazole troches, nystatin pastilles, and nystatin oral suspension are effective
for mild-to-moderate erythematous and pseudomembranous candidiasis.
• Increased risk of caries can be avoided by using a nystatin oral suspension
(100,000 units/5 ml, rinsing mouth, and expectorating 3 times/day).
• Chlorhexidine 0.12% oral rinses do not contain a cariogenic substrate and may be
similarly effective.
• Topical amphotericin B can also be used in the treatment for resistant candidiasis
and can be prepared by dissolving 50 mg in 500 ml of sterile saline (0.1 mg/ml).
• Clotrimazole 1% cream, miconazole or ketoconazole 2% cream, and nystatin
ointment are useful medications for angular cheilitis and for application to a
removable denture base when there is candidal infection involving the underlying
mucosa.
61
• SYSTEMIC TREATMENT
• imidazole (ketoconazole) and triazole (fluconazole and itraconazole) antifungal
medications.
• Fluconazole is given in the dose of 100–200 mg/day.
• The duration of treatment with oral imidazoles usually is around 7–10 days but in
cases of suspicion of esophageal involvement, the duration can be extended to 21
days.
• As per the recent guidelines there is no role of prophylaxis for candidiasis in HIV
patients.
62
• 2.Histoplasmosis:
• Granulomatous fungal disease caused by Histoplasma capsulatum.
• The clinical presentation ranges from an asymptomatic or mild lung infection to
an acute or chronic disseminated form.
• Oral histoplasmosis appears as chronic ulcerated areas located on the dorsum of
the tongue, palate, floor of the mouth, and vestibular mucosa. Focal or multiple
sites can be involved.
• In AIDS patients, histoplasmosis is rarely curable, but it can be controlled with
long-term suppressive therapy consisting of the administration of amphotericin B
and ketoconazole.
63
• 3.Cryptococcosis:
• Oral manifestations are quite unusual and only two cases have been reported in the
literature.
• The lesions consist of ulcerations of the oral mucosa, but the clinical diagnosis of
oral cryptococcus may be difficult since other microbial infections and trauma may
show similar appearances. Tissue biopsy may be required for the diagnosis and
treatment involves use of amphotericin B.
64
VIRAL INFECTIONS
• 1.Oral hairy leukoplakia:
• lateral surface of the tongue, extend to the dorsal and ventral surfaces
• Lesions may be variably sized and may appear as vertical white
striations,corrugations, or as flat plaques, or raised, shaggy plaques with hair-like
keratin projections.
• bilateral and asymptomatic.
• Associated with a localized Epstein–Barr virus (EBV)
infection and occurs most commonly in individuals
whose CD4 lymphocyte count is less than 200/μl.
• This condition usually does not require treatment but use of oral acyclovir, topical
podophyllum resin, retinoids, and surgical removal have all been reported as
successful treatments.
65
• 2.Herpes simplex and varicella zoster virus infections:
• Responsible for both primary and recurrent infections
of the oral mucosa.
• Oral manifestations, represented by diffuse mucosal
ulcerations
• Accompanied by fever, malaise, and cervical lymphadenopathy.
• Ulcerations that follow the rupture of vesicles are painful
• Recurrent HSV usually appears in keratinizing oral mucosa
(i.e., palate, dorsum of tongue, and gingiva) as ulcerations
but in most HIV-seropositive patients, this rule is not followed.
• Contact with the varicella zoster virus (VZV) may result
in varicella (chicken pox) as a primary infection and
herpes zoster (shingles) as a reactivated infection.
66
• 3.Cytomegalovirus
• CMV-related oral ulcerations, are a recognized complication of HIV infection.
• The diagnosis of oral CMV is based upon the presence of large intranuclear and
smaller cytoplasmic CMV inclusions in the endothelial cells at the base of the
ulcerations.
• These infections usually manifest in stage IV of the infection when there is advanced
immunosupression with a CD4 count below 50.
• The drug of choice for CMV infection is intravenous gancyclovir.
• 4.Human Papilloma Virus
• Human papilloma virus (HPV) causes a focal epithelial and connective tissue
hyperplasia, forming an oral wart.
• In HIV-infected patients, oral HPV-related lesions have a papillomatous appearance,
either pedunculated or sessile, and are mainly located on the palate, buccal mucosa,
and labial commissure.
67
Bacterial Infections
• 1.Linear erythematous gingivitis:
• This entity appears as a band of marginal gingival erythema, often with petechiae.
• It is typically associated with no symptoms or only mild gingival bleeding and mild
pain.
• Histological examination fails to reveal any significant inflammatory response,
• Oral rinsing with chlorhexidine gluconate often reduces or eliminates the erythema
and may require prophylactic use to avoid recurrence.
68
• 2.Necrotizing ulcerative periodontitis (NUP):
• This periodontal lesion is characterized by
generalized deep osseous pain,
significant erythema ,spontaneous bleeding,
and rapidly progressive destruction
of the periodontal attachment and bone.
• The destruction is progressive and can result in loss of the entire alveolar process in
the involved area.
• Patients also have severe halitosis.
• More than 95% of patients with NUP have a CD4 lymphocyte count of less than
200/mm3.
• Treatment consists of rinsing twice daily with chlorhexidine gluconate 0.12%,
metronidazole (250 mg orally four times daily for 10 days), and periodontal
debridement, which is done after antibiotic therapy has been initiated.
69
• 3.Syphilis:
• It is an uncommon cause of intraoral ulceration, even in HIV infection.
• It is a chronic, nonhealing, deep, solitary ulceration; often clinically indistinguishable
from that due to tuberculosis, deep fungal infection, or malignancy.
• Combination treatment with penicillin, erythromycin, and tetracycline is the
treatment of choice, the dosage and duration of the treatment depending on the
presence or absence of neurosyphilis.
70
NEOPLASMS
• 1.Kaposi's sarcoma:
• It is the most common intraoral malignancy associated with HIV infection. The
lesion may appear as a red-purple macule, an ulcer, or as a nodule or mass.
• KS is especially common among homosexual and bisexual males and is rarely found
in HIV-infected women.
• When only a few lesions exist and the lesions are small (< 1 cm), intralesional
chemotherapy with vinblastine sulfate or sclerotherapy with 3% sodium tetradecyl
sulfate is usually effective.
71
• 2.Non-Hodgkin's lymphoma:
• NHL is the most common lymphoma associated with HIV infection and is usually
seen in late stages with CD4 lymphocyte counts of less than 100/mm3.
• It appears as a rapidly enlarging mass, less commonly as an ulcer or plaque, and
most commonly on the palate or gingivae.
• A histological examination is essential for diagnosis and staging.
• Prognosis is poor, with mean survival time of less than 1 year, despite treatment
with multidrug chemotherapy.
72
Immune mediated oral lesions
• 1.Aphthous ulcers:
• They are the most common immune-mediated HIV-related oral disorder, with a
prevalence of approximately 2–3%. These ulcers are either large solitary or multiple,
chronic, deep, and painful often lasting much longer in the seronegative population
and are less responsive to therapy.
• Treatment - topical steroid such as clobetesol
when the lesions are accessible
• dexamethasone oral rinse when not accessible.
• Systemic glucocorticosteroid -prednisone 1 mg/kg
• Alternative therapies such as dapsone 50–100 mg daily
and thalidomide 200 mg daily for 4 weeks should be considered in recalcitrant cases.
73
• 2.Xerostomia:
• side effect of antiviral medications or other medications commonly , like angiolytics,
antifungals, etc.
• significant risk factor for caries and can lead to rapid dental deterioration.
• lead to oral candidiasis, mucosal injury, and dysphagia, and is often associated with
pain and reduced oral intake of food.
• oral pilocarpine often provides improved salivary flow and consistency.
74
Parotid Gland Disease
• gland enlargement and diminished flow of secretions.
• Histologically, there may be lymphoepithelial infiltration and benign cyst formation.
• The enlargement typically involves the tail of the parotid gland or, less commonly,
the submandibular gland, and it may present uni- or bilaterally with periods of
increased or decreased size.
• Occasional swelling can be managed simply by repeated aspiration and rarely is
radical removal of the gland necessary.
• The pathophysiological mechanism is not known, though cytomegalovirus has been
suggested to play a role.
75
76
• HIV prevalence going down in Odisha. The HIV prevalence is going down in
Odisha. Compared to a HIV positive rate of 0.7 per cent in 2014-2015, around 0.3
per cent people in state are HIV positive in 2018-19.
• 16,011 AIDS patients in Ganjam
• 887 pregnant women are HIV positive in the district
• Polasara block has 1,348 AIDS patients, the highest in the district
• 12,195 AIDS patients are being given pension of Rs 500 per month
• Srilanka eradicated both HIV and syphillis
• CD4 Cells normal-500-1500
77
Diagnosis of AIDS
• Control of AIDS
• HIV Survillience
• NACO,NACP
• National Blood Policy
• Recent Developments
• The future
• Summary
78
PART 2
Diagnosis of AIDS
• CLINICAL
• I. WHO case definition for AIDS surveillance
• at least 2 of the following major signs are present in combination with at least 1 of
the minor signs
• Major signs
79
weight loss 10% of body
weight
chronic diarrhoea
for more than 1 month
prolonged fever for
more than 1 month
(intermittent or constant).
persistent cough
generalized pruritic
dermatitis
history of herpes zoster
oropharyngeal candidiasis
chronic progressive
or disseminated
herpes simplex infection
generalized lymphadenopathy.
Minor Signs
CHILDREN
• Major signs
• weight loss or abnormally slow growth
• chronic diarrhoea for more than 1 month
• prolonged fever for more than 1 month.
• Minor signs
• generalized lymph node enlargement
• oropharyngeal candidiasis
• recurrent common infections, e.g. ear infection,
• pharyngitis
• persistent cough
• generalized rash
80
• II. Expanded WHO case definition for AIDS surveillance
• For the purposes of AIDS surveillance an adult or adolescent ( > 12 years of age) is
considered to have AIDS if a test for HIV antibody gives a positive result, and one or
more of the following conditions are present :
• less than 10% body weight loss
• cryptococcal meningitis
• pulmonary or extra- pulmonary tuberculosis
• Kaposi sarcoma
• neurological impairment
• candidiasis of the oesophagus
• recurrent episodes of pneumonia
81
82
WHO CLINICAL STAGING OF HIV INFECTION
ADULTS CHILDREN
CLINICAL STAGE 1
Asymptomatic Asymptomatic
Persistent generalized lymphadenopathy Persistent generalized lymphadenopathy
82
Lymph nodes are larger than one centimetre in diameter, in
two or more sites other than the groin area for a period of at
least three months.
83
CLINICAL STAGE 2-ADULTS CHILDREN
-Moderate unexplained weight loss (<10% of
presumed or measured body weight)
-Recurrent respiratory tract infections (sinusitis,
tonsillitis, otitis media, pharyngitis)
-Herpes zoster
-Angular cheilitis
-Recurrent oral ulceration
-Papular pruritic eruption
-Fungal nail infections
-Seborrhoeic dermatitis
-Unexplained persistent hepatosplenomegaly
-Recurrent or chronic upper respiratory tract
infections(otitis media, otorrhoea, sinusitis,
tonsillitis)
-Herpes zoster
-Lineal gingival erythema
-Recurrent oral ulceration
-Papular pruritic eruption
-Fungal nail infections
-Extensive wart virus infection
-Extensive molluscum contagiosum
-Unexplained persistent parotid enlargement
84
CLINICAL STAGE III ADULTS CHILDREN
Unexplained severe weight loss (>10% of
presumed or measured body weight)
Unexplained chronic diarrhoea for longer
than 1 month
Unexplained persistent fever (intermittent or
constant for longer than 1 month)
Persistent oral candidiasis
Oral hairy leukoplakia
Pulmonary tuberculosis
Severe bacterial infections (such as pneumonia,
empyema, pyomyositis, bone or joint infection,
meningitis, bacteraemia)
Unexplained moderate malnutritionb
not adequately
responding to standard therapy
Unexplained persistent diarrhoea (14 days or more)
Unexplained persistent fever (above 37.5°C,
intermittent
or constant, for longer than one 1 month)
Persistent oral candidiasis (after first 6 weeks of life)
Oral hairy leukoplakia
Lymph node tuberculosis
Pulmonary tuberculosis
Severe recurrent bacterial pneumonia
85
CLINICAL STAGE III ADULTS CHILDREN
Acute necrotizing ulcerative stomatitis,gingivitis or
periodontitis
Unexplained anaemia (<8 g/dl),
neutropaenia (<0.5 x 109/l) and/or chronic
thrombocytopaenia (<50 x 109/l)
Acute necrotizing ulcerative gingivitis or
periodontitis
Unexplained anaemia (<8 g/dl), neutropaenia
(<0.5 x 109/l) or chronic thrombocytopaenia
(<50 x 109/l)
86
CLINICAL STAGING IV ADULTS CHILDREN
HIV wasting syndrome
Pneumocystis (jirovecii) pneumonia
Recurrent severe bacterial pneumonia
Chronic herpes simplex infection (orolabial,
genital or anorectal of more than 1 month’s
duration or visceral at any site)
Oesophageal candidiasis (or candidiasis of
trachea, bronchi or lungs)
Extrapulmonary tuberculosis
Kaposi sarcoma
Cytomegalovirus infection (retinitis or
infection of other organs)
Unexplained severe wasting, stunting or severe
malnutritiond
not responding to standard therapy
Pneumocystis (jirovecii) pneumonia
Recurrent severe bacterial infections (such as
empyema, pyomyositis, bone or joint infection,
meningitis, but excluding pneumonia)
Chronic herpes simplex infection (orolabial or
cutaneous of more than 1 month’s duration or
visceral at any site)
Oesophageal candidiasis (or candidiasis of trachea,
bronchi or lungs)
87
Extrapulmonary cryptococcosis, including
meningitis
Disseminated nontuberculous mycobacterial
infection
Progressive multifocal leukoencephalopathy
Chronic cryptosporidiosis
Chronic isosporiasis
Disseminated mycosis (extrapulmonary
histoplasmosis, coccidioidomycosis)
Lymphoma (cerebral or B-cell non-Hodgkin)
Symptomatic HIV-associated nephropathy or
cardiomyopathy
Recurrent septicaemia (including
nontyphoidal Salmonella)
Extrapulmonary tuberculosis
Kaposi sarcoma
Cytomegalovirus infection (retinitis or infection of
other organs with onset at age more than 1 month)
Central nervous system toxoplasmosis (after the
neonatal period)
HIV encephalopathy
Extrapulmonary cryptococcosis, including meningitis
Disseminated nontuberculous mycobacterial
infection
Progressive multifocal leukoencephalopathy
Chronic cryptosporidiosis (with diarrhoea)
Chronic isosporiasis
Disseminated endemic mycosis (extrapulmonary
histoplasmosis, coccidioidomycosis, penicilliosis)
Laboratory Diagnosis
• Screening tests
• A person whose blood contains HIV antibodies is said to be HIV-positive, or
seropositive,
• screening test must be sensitive enough to identify all "true positives",
• specific enough to record few "false positives".
• The first kind of test is normally the ELISA.
• The confirmatory test-Western Blot is a highly specific test
• Virus isolation
• Absolute CD4 cell count
• CD4 Lymphocyte percentage
• HIV Viral load tests
• p24 antigen
88
89
90
Western blotting (protein blotting or
immunoblotting) is a rapid and sensitive
assay for detection and characterization of
proteins. It is based on the principle of
immunochromatography where proteins are
separated into polyacrylamide gel according
to their molecular weight
CONTROL OF AIDS
• Prevention
• Antiretroviral treatment
• specific prophylaxis
• primary health care
91
PREVENTION OF AIDS
• Education
• Combination of HIV Prevention-
biomedical,behavioural and structural
interventions
• Male and female condom
• needle syringe programme
• opiod substitution therapy
• voluntary medical male circumcision
• Blood borne HIV transmission
92
ANTIRETROVIRAL TREATMENT
93
Nucleoside
reverse
transcriptase
inhibitors
(NRTls)
Nucleotide
reverse
transcriptas
e inhibitors
(NtRTls)
Non-nucleoslde
reverese
transcriptase
Inhibitors
(NNRTls)
Protease
inhibitors (Pis)
lntegrase
strand
transfer
inhibitors
(INSTls)
Abacavir
(ABC)
Didanosine
(ddl)
Emtricitabine
(FTC)
Lamivudine
(3TC)
Stavudine
(d4T)
Zidovudine
(AZT)
Tenofovir
(TDF)
Efavirenz (EFV)
Etravirine
(ETV)
Nevirapine
(NVP)
Atazanavir +
ritonavir
(ATV/r)
Darunavir +
ritonavir
(DRV)r)
Fos-amprenavir
+ ritonavir
(FPV/r)
lndinavir +
ritonavir (IDV/r)
Lopinavir/rilona
vir (LPV/r)
Saquinavir +
ritonavir
(SQV/r)
Raltegravir
(RAL)
WHO Recommended ARV treatment
1.When to start ART?
94
( > 19 years old) All adults regardless of CD4 cells
Priority- severe or advanced HIV clinical
disease (WHO clinical stage 3 or 4) and
adults with a CD4 count ≥ 350 cells/mm3 .
Pregnant and breastfeeding women All adults
Adoloscents (10-19 years) all adolescents
Priority - ART should be initiated in all
adolescents with severe or advanced HIV
clinical disease (WHO clinical stage 3 or 4)
and adolescents with a CD4 count
≥350 cells/mm3•
• In children
• all children infected with HIV below five years of age
• Infants diagnosed in the first year of life
• Children infected with HIV one year to less than five years of age
• all children infected with HIV five years of age and older with CD4 cell count ≤500
cells/mm3, regardless of WHO clinical stage.
• CD4 count ≤350 cells/mm3
95
• Timing of ART for adults and children with TB
• all TB patients living with HIV regardless of CD4 count.
• TB treatment should be initiated first,followed by ART within the first 8 weeks of
treatment.
• CD4 counts less than 50 cells/mm3 should receive ART within the first two weeks of
initiating
96
• What to Start?
• First-line ART for adults
• consist of two nucleoside reversetranscriptase inhibitors (NRTIs) plus a non-
nucleoside reverse-transcriptase inhibitor (NNRTI).
• TDF + 3TC (or FTC) + EFV as a fixed-dose combination is recommended as the
preferred option to initiate ART (strong recommendation, moderate-quality
evidence).
• If TDF + 3TC (or FTC) + EFV is contraindicated or not available, one of the
following options is recommended:
• AZT + 3TC + EFV
• AZT + 3TC + NVP
• TDF + 3TC (or FTC) + NVP
97
• First-line ART for pregnant and breastfeeding women and their infants
• fixed-dose combination of TDF + 3TC (or FTC) + EFV
• Infants of mothers who are receiving ART and are breastfeeding should receive six
weeks of infant prophylaxis with daily NVP.
• If infants are receiving replacement feeding, they should be given four to six weeks of
infant prophylaxis with daily NVP (or twice-daily AZT).
• Infant prophylaxis should begin at birth or when HIV exposure is recognized
postpartum
98
• First-line ART for children 3 years of age and older (including adolescents)
• EFV is the preferred NNRTI
• NVP is the alternative
• For children infected with HIV three years to less than 10 years old and adolescents
weighing less than 35 kg
• ABC + 3TC
• AZT or TDF + 3TC (or FTC)
• For adolescents infected with HIV (10 to 19 years old) weighing 35 kg or more,
• TDF + 3TC (or FTC)
• AZT + 3TC
• ABC + 3TC
99
• MONITORING THE RESPONSE TO ART AND DIAGNOSING TREATMENT
FAILURE
• 6months and 12 months
• Viral load is recommended
• CD4 count and clinical monitoring
• Dried blood spot specimens using venous or capillary whole blood can be used to
determine the HIV viral load.
100
• In adults and adolescents (includes pregnant and breastfeeding women)
• Second-line ART for adults should consist of two nucleoside reverse-transcriptase
inhibitors (NRTIs) + a ritonavir-boosted protease inhibitor (PI).
• The following sequence of second-line NRTI options is recommended:
• After failure on a TDF + 3TC (or FTC) -based first-line regimen, use AZT + 3TC as
the NRTI backbone in second-line regimens.
• After failure on an AZT or d4T + 3TC-based first-line regimen, use TDF + 3TC (or
FTC) as the NRTI backbone in second-line regimens.
101
• In children (including adolescents)
• After failure of a first-line NNRTI-based regimen, a boosted PI plus two NRTIs are
recommended for second-line ART
• LPV/r is the preferred boosted PI
• After failure of a first-line LPV/r-based regimen, children younger than 3 years
should remain on their first-line regimen
• After failure of a first-line LPV/r-based regimen, children 3 years or older should
switch to a second-line regimen
• NNRTI plus two NRTIs
• EFV is the preferred NNRTI
102
• After failure of a first-line regimen of ABC or TDF + 3TC (or FTC),
• Preferred- ART is AZT + 3TC
• After failure of a first-line regimen containing AZT or d4T + 3TC (or FTC)
• preferred - ART is ABC or TDF + 3TC (or FTC)
• Third Line ART
• National programme should develop policies for third-line ART.
• Include new drug with minimal risk of cross-resistance to previously used regimens.
such as INSTls and second-generation NNRTls and Pis.
• Patients on a failing second-line regimen with no new ARV options should continue
with a tolerated regimen.
103
• Post-exposure prophylaxis (PEP)
• consists of a comprehensive set of services
• the short term (28 days) provision of antiretroviral drugs
• ELIGIBILTY
• ideally within 72 hours.
• status of the source
• Exposures
• a. parenteral or mucous membrane exposure
• b. bodily fluids
• Exposures not requiring PEP
• HIV positive
• HIV negative
104
105
Post-exposure
prophylaxis ARV
regimens – adults and
adolescents
Doses of ARV
drugs for HIV
post-exposure
prophylaxis for
adults and
adolescents
106
Post-exposure
prophylaxis ARV
regimens – children
(≤10 years old)
Prescribed
frequency
Adherence
support
107
Co-trimoxazole
(sulfamethoxazole
and trimethoprim)
• SPECIFIC PROPHYLAXIS
• Primary prophylaxis against P carinii pneumonia should be offered to patients with
CD4 count below 200 cells/µL.
• The regimens available are trimethoprim sulfamethoxazole, aerosolized pentamidine
and dapsone.
• M. auium complex occurs in at least one-third of AIDS patients.
• Rifabutin -Mauium intracelLulare with less than 200 CD4 cell/µL.
• 300 mg Isoniazid- M. tuberculosis
• Kaposi's sarcoma -interferon, chemotherapy or radiation.
• Cytomegalovirus retinitis - ganciclovir,
• cryptococcal meningitis - fluconazole
• Esophageal candidiasis - fluconazole ,ketoconazole
• Herpes simplex infection and herpes zoster - cyclovir or foscamet.
108
HIV SURVILLIENCE
The surveillance system would include:-
(a) HIV Sentinel Surveillance
(b) AIDS Case Surveillance
(c) STDs Surveillance; and
(d) Behavioral Surveillance.
The types of HIV surveillance are :
(a) HIV Seintinel Surveillance,
(b) HIV Sero- Surveillance,
(c) AIDS Case Surveillance,
(d) STD Surveillance,
(e) Behavioural Surveillance
(f) Integration with surveillance of other diseases like tuberculosis etc.
109
• The objectives of the surveillance are as follows :
• 1. To determine the level of HIV infection among general population as well as high-
risk groups in different states;
• 2. To understand the trends of HIV epidemic among general population as well as
high-risk groups in different states;
• 3. To understand the geographical spread of HIV infection and to identify emerging
pockets;
• 4. To provide information for prioritization of programme resources and evaluation
of programme impact; and
• 5. To estimate HIV prevalence and HIV burden in the country.
110
• HIV sentinel surveillance for HIV
• 1994 in 55 sentinel sites ,1998-180
• The 14th HIV sentinel surveillance at ANC sentinel sites was implemented from 1st
January 2015 to 31st March 2015 at 572 districts.
Number of sentinel sites
111
Site type 2008-09 2010-11 2016-17
STD
ANC
ANC (rural)
ANC (youth)
IDU
MSM
FSW
Migrant
TG
Truckers
TB
Fisher-
folk/seamen
217
498
162
8
61
67
194
8
1
7
-
-
184
506
182
8
79
96
262
20
3
20
-
-
829
87
89
245
27
18
28
112
• The 15th round of HSS
• 2017 at 1323 sentinel sites-
• 829 sites Antenatal Clinic (ANC) clinic attendees and
• 494 sites among high-risk groups & bridge populations: Female Sex Workers
(FSW),Men having Sex with Men (MSM), Injecting Drug Users (IDU),
Hijra/Transgender People (H/TG), Single Male Migrants (SMM) & LongDistance
Truckers (LDT).
• 4.45 lakh blood specimens were tested across all population groups during the 15th
round of HSS.
• The highest prevalence recorded in the 2017 rounds of HSS was among IDU
(6.26%, 95% CI: 5.92-6.59), followed by H/TG (3.14%, 95%CI:2.61-3.66), MSM
(2.69, 95% CI: 2.47-2.91), FSW (1.56%, 95% CI: 1.46-1.66), LDT (0.86%, 95% CI:
0.64-1.07) and SMM (0.51%, 95% CI: 0.34-0.68).
113
http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf
• Thirteen states have recorded an ANC HIV prevalence which is more than the
national average.
• Mizoram (1.19%), Nagaland (0.82%), Meghalaya (0.73%), Tripura (0.56%)
• and Manipur (0.47%) were among the highest.
• Gujarat and Andhra Pradesh HIV prevalence in the range of 0.41% to 0.44% among
ANC clinic attendees
• Overall 56 sentinel sites recorded HIV prevalence of > 1%
• Bihar,Chhattisgarh, Delhi, Gujarat, Jharkhand, Odisha, Rajasthan and Uttar Pradesh.
• Fourteen sites recorded an HIV prevalence of > 2%
• Bihar, Chhattisgarh, Odisha, Rajasthan and Uttar Pradesh.
114
http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf
• Of the 829 sentinel sites for ANC, 561 are consistent sites, and analysis of these sites
indicates a declining trend at the national level.
• The implementation of HSS in the FSW typology was completed at 245 sites across
thirty-two states. Nine states recorded HIV prevalence of more than national average
(1.56%, 95% CI: 1.46-1.66) while 17 sites recorded an HIV prevalence of >5% with
a majority of them in Karnataka ,Maharashtra and Telangana
• Among MSM, HSS was conducted at 89 sites across 26 states with thirteen sites
recording prevalence of more than 5%. In total, 12 states recorded HIV prevalence of
more than the national average (2.69, 95% CI:2.47-2.91) with more than 5%
HIVprevalence in the states of Manipur(8.40%),Nagaland (7.66%) and Karnataka
(5.40%).
115
http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf
• The national HIV prevalence among the Injecting Drug Users was the highest among
all population groups (6.26%, 95%CI: 5.92-6.59).
• 87 sites spread across 26 states.
• A total of nine states recorded an HIV prevalence of >5%
• Mizoram (19.81%), Delhi (16.21%), Punjab (12.09%),Chhattisgarh (10.77%), West
Bengal (10.76%), Uttarakhand (8.98%),Tripura (8.55%), Manipur (7.66%) and
Madhya Pradesh (5.33%).
• Thirty sites recorded HIV prevalence of >5%, with a majority of them in the states of
Manipur, Punjab and Mizoram
116
http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf
• A major expansion of H/TG sites was undertaken in this round of surveillance, with
18 sites participating in this round of HSS,
• The HIV prevalence among this population group was the second highest (3.14%,
95%CI: 2.61-3.66)
• The highest prevalence among H/TG was noted at 10.9% in the district of North East
Delhi. Other than North East Delhi, t
• prevalence of more than 5%: Kolkata (7.28%), Thane (6.80%) and Hyderabad
(6.47%).
117
http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf
• Counselling and HIV testing services
• 1.Integrated Counselling and Testing Centres (ICTC).
• 2. Prevention of parent-to-child transmission of HIV (PPTCT).
• 3. HIV/tuberculosis collaborative activities.
118
Level of HIV counselling and testing services
119
Community
level
Village level
PHCs
Sub district level
civil hospitals
State and district level
HIV screening
Standalone ICTCs and facility ICTCs
Standalone ICTCs and facility ICTCs
Standalone ICTCs
• The essential package of PPTCT services in India are as follows :
• 1. Routine offer of HIV counselling and testing to all pregnant women enrolled into
antenatal care, with an 'opt out'option.
• 2. Ensuring involvement of spouse and other family members, and move from an
"ANC-Centric" to a "Family-Centric" approach.
• 3 . Provision of life-long ART (TDF+3TC+EFV) to all pregnant and breast-feeding
HIV infected women, regardless of CD4 count and clinical stage of
HIVprogressic>n.
• 4 . Promotion of institutional deliveries of all HIV infected pregnant women.
• 5. Provision of care for associated conditions (STJ/RTI, TB and other opportunistic
infections). 120
• 6. Provision of nutrition, counselling and psychosocial support for HIV infected
pregnant women.
• 7. Provision of counselling and support for initiation of exclusive breast-feeds within
an hour of delivery as the preferred option and continued for 6 months.
• 8. Provision of ARV prophylaxis to infants from birth upto a minimum of 6 months.
• 9. lntegrating follow-up of HIV-exposed infants into routine healthcarn services
including immunization.
121
• 10. Ensuring initiation of Co-trimoxazole Prophylactic Therapy (CPT) and Early
Infant Diagnosis (EID) using HIV-DNA PCR at 6 weeks of age onwards, as per the
EID guidelines.
• 11. Strengthening community follow-up and outreach through local community
networks to support HIVpositive pregnant women and their families.
122
NATIONAL AIDS CONTROL PROGRAM
• launched in the year 1987.
• National AIDS Control Organization (NACO) -a separate wing to implement and
closely monitor the various components of the programme.
AIMS OF NACP
• to prevent further transmission of HIV
• to decrease morbidity and mortality associated with HIV infection
• to minimize the socio-eonomic impact resulting from HIV infection.
123
• MILESTONES OF NACO
124
YEAR MILESTONES
1986 -First case of HIV detected.
- AIDS Task Force set up by the ICMR.
- National AIDS Committee established under the Ministry of Health
1990 Medium Term Plan launched for four states and the four metros
1992 NACP-1 launched to slow down the spread of HIV infection.
- National AIDS Control Board constituted.
- NACO set-up.
1999 NACP- II begins, focussing on behaviour change, increased decentralization and NGO
involvement.
- State AIDS Control Societies established.
2002 -National AIDS Control Policy adopted.
- National Blood Policy adopted.
2004 Anti retroviral treatment inititated
125
2006 National Council on AIDS constituted under chairmanship of the Prime Minister.
- National Policy on Paediatric ART formulated.
2007 NACP-lll launched for 5 years (2007- 2012).
2014 NACP-IV launched for 5 years (2012-2017).
2017 National strategic plan for HIV/AIDS and STIs 2017-2024
• NACP IV
• goal of NACP-IV is to halt and reverse the epidemic in India over the next 5 years by
integrating programmes for prevention, c.are, support and treatment.
• The package of services under NACP-IV are as follows :
• 1. Prevention services
• 2.Care ,support and treatment services
• COMPONENTS
• Intensifying and Consolidating Prevention services with a focus on HRG and
vulnerable populations
• Expanding IEC services for (a) general population and (b) high risk groups with a
focus on behavior change and demand generation
• Comprehensive Care, Support and Treatment
• Strengthening institutional capacities
126
http://naco.gov.in/nacp-iv-components
NATIONAL AIDS CONTROL ORGANISATION
• Division under ministry of health and family welfare 1992
• head-additional secretary
• finance division-director-finance
• admin and procurement -joint secretary
127
Joint secretary
targeted
interventions
and laws
basic services
STI/RTI
Management
Blood safety lab services
care support
and treatment
admin
procrurement
finance
Additional
secretary
• Care,Support and treatment
• 90-90-90 aims at ending AIDS by 2030
• 90% know their status
• 90 %are on ART
• 90 %have viral suspension
• march 2017- 530 ART centres ,1108 link ART centres ,17centres of excellence,7
paediatric centres of excellence, 52'. ART Plus centres and 350 care and support
centres
128
Modes of treatment services
129
CoE &
ART Plus
ART centres
Link ART centres and LAC
plus centres
Select medical colleges
medical colleges and district level hospital
sub district level hospitals and CHC
• Services provided
1.first line ART
2.Second line ART
3.Third line ART
4.National paediatric HIV /AIDS initiative
5.Paediatric second line ART
6.Following up and monitoring
7.Managment of opportunistic infections
8.targeted interventions for high risk groups
9.link worker scheme
10.condom promotion
11.STD control programme
12.Pre-Packed STI/RTI Color coded kits
130
National Strategic Plan and STI 2017-2024
131
132
133
134
The 15th Memorandum of Understanding
(MoU) was signed between National
AIDS Control Organization and
Department of Internal Security on 1st
September, 2017 at the Conference Hall,
NACO
a) Reach large number of Central Armed Police Forces with information on preventions and control of STI/HIV/AIDS;
b) Facilitate building of humane perspective and appropriate skills among police force to reduce stigma and discrimination
against PLHIV and MARPs,
c) Integrate STI/ HIV/AIDS services in the medical and health services under the control of Department of Internal
Security, Ministry of Home Affairs and
d) Direct all forces under purview of Department of Internal Security to include the issue of HIV/AIDS in the training.
http://naco.gov.in/nacoevents/memorandum-understanding-mou-between-naco-and-department-internal-security
• Community Based Testing (CBT) in Rajasthan
• RajasthanState AIDS Society (RSACS), inaugurated the first “Community Based Testing (CBT)”,
facility in Indian Public Educational Society (IPES), TI Project, Bhilwara on 12th May’2017.
135
http://naco.gov.in/documentsreports
136
Red Ribbon Express'1 December 2007
Seven coaches carrying HIV prevention
messages will traverse over 27,000 km making
180 halts, covering 166 districts across the
country, reaching out to crores of people in over
50,000 villages for scaling up ground level
mobilization activities.
the government also announced provision of
free 2nd line treatment in two centres of the
country.Tambaram Hospital in Chennai and JJ
Hospital in Mumbai
http://naco.gov.in/press-release
National Blood Policy,2002
• OBJECTIVES
1.To reiterate firmly the Govt. commitment to provide safe and adequate quantity of
blood, blood components and blood products.
• A national blood transfusion Programme shall be developed
• Trading in blood i.e. Sale & purchase of blood shall be prohibited.
• Transfusion Services shall be promoted
• Necessary amendments shall be made in the Drugs & Cosmetics Act/Rules to
provide special licenses to small garrison units.
137
• 2.To make available adequate resources to develop and reorganise the blood
transfusion services in the entire country.
• National & State/UT Blood Transfusion Councils shall be supported/strengthened
financially
• Efforts shall be directed to make the blood transfusion service viable through non-
profit recovery system
138
• 3.To make latest technology available for operating the blood transfusion services
and ensure its functioning in an updated manner.
• Minimum standards for testing, processing and storage shall be set and ensured.
• A Quality System Scheme shall be introduced
• Regular proficiency testing of personnel shall be introduced in all the blood centres.
• An External Quality Assessment Scheme (EQAS) approved by the National Blood
Transfusion Council shall be introduced
• Efforts shall be made towards indigenisation of kits, equipment and consumables
used in blood banks.
• Use of automation shall be encouraged
• A mechanism for transfer of technology shall be developed
• Each blood centre shall develop its own Standard Operating Procedures
• Guidelines for Control' and disposal of biohazardous waste as per the provisions of
the existing Biomedical Wastes (Management & Handling) Rules - 1996 under the
Environmental Protection Act - 1986. 139
• 4.To launch extensive awareness programmes for donorinformation, education,
motivation, recruitment and retention in order to ensure adequate availability of safe
blood.
• Efforts shall be directed towards recruitment and retention of voluntary, non-
remunerated blood donors
• Enrolment of safe donors
• State/UT Blood Transfusion Councils shall recognise the services of regular
voluntary non-remunerated blood donors and donor organisers appropriately.
• National/State/UT Blood Transfusion Councils shall develop and launch an IEC
campaign
• National / State / UT blood transfusion councils shall involve other departments /
sectors for promoting voluntary blood donations
140
• 5.To encourage appropriate clinical use of blood and blood products.
• Blood shall be used only when necessary
• National Guidelines on 'Clinical use of Blood' shall be made available and updated as
required from time to time.
• Effective and efficient clinical use of blood shall be promoted
• Education and training in effective clinical use of blood shall be organised.
• Blood and its components shall be prescribed only by a medical practitioner
• Availability of blood components shall be ensured
• Appropriate steps shall be taken to increase the availability of plasma fractions
• Adequate facilities for transporting blood and blood products
• Guidelines for management of blood supply during natural and man made disasters
shall be made available
141
• 6.To strengthen the manpower through Human Resource Development
• Transfusion Medicine shall be treated as a speciality.
• Transfusion Medicine shall be incorporated as one of the subjects.
• In-service training programmes shall be organised for all categories
• Appropriate modules for training of Donor Organisers/Donor Recruitment
Officers shall be developed
• Short orientation training cum advocacy programmes on donor motivation
• Based Organisations(CBOs) and NGOs who wish to participate in Voluntary Blood
Donor Recruitment Programme.
• Inter-country and intra-country exchange for training and experience of personnel
associated with blood centres
• States/UTs shall create a separate cadre and opportunities for promotions
142
• 7.To encourage Research & Development in the field of Transfusion Medicine and
related technology.
• A corpus of funds shall be made available to NBTC/SBTCs to facilitate research in
transfusion medicine and technology related to blood banking.
• A technical resource core group at national level shall be created to co-ordinate
research and development in the country.
• Multi-centric research initiatives on issues related to Blood Transfusion shall be
encouraged.
• To take appropriate decisions and/or introduction of policy initiatives on the basis of
factual information
• Computer based information and management systems shall be developed which can
be used by all the centres regularly to facilitate networking
143
• 8.To take adequate regulatory and legislative steps for monitoring and evaluation of
blood transfusion services and to take steps to eliminate profiteering in blood banks
• For grant/renewal of blood bank licenses
• Fresh licenses to stand-alone blood banks in private sector shall not be granted.
• A separate blood bank cell shall be created under a senior officer not below the rank
of DDC(I) in the office of the DC(I) at the headquarter.
• As a deterrent to paid blood donors who operate in the disguise of replacement
donors, institutions who prescribe blood for transfusion shall be made responsible for
procurement of blood for their patients through their affiliation with licensed blood
centres.
• States/UTs shall enact rules for registration of nursing homes wherein provisions
for affiliation with a licensed blood bank for procurement of blood for their patients
shall be incorporated.
144
National Blood Transfusion Council (NBTC)
• In accordance with the directive of the Supreme Court, NBTC was constituted in
1996
• Blood Transfusion Services have to ensure that Blood/ Components (Whole Blood/
Packed Red Cells/ Plasma/ Platelets) are
• Available
• Accessible
• Affordable
• Safe
• Of standard quality
145
OBJECTIVES OF NBTC
• to promote voluntary blood donation,
• ensure safe blood transfusion,
• provide infrastructure to blood centres,
• develop human resource and
• formulate and implement the Blood
Policy.
146
MILESTONES OF BLOOD TRANSFUSION
• 1945 : First blood bank in Kolkata
• 1954 : Voluntary blood donation began.
• 1975 : Blood bank licensing process started with HBV, Syphilis & Malaria
• 1988 : HIV testing made mandatory
• 1989 : MD Programme
• 1992 : BTS under EMR division of DGHS
• 1992 : NACO started and BTS shifted under NACO as BS Division
• 1996 : Supreme court Judgement (PIL filed by common causes vs GoI)
• 1996 : NBTC and SBTC formed
• 1997 : Mandatory licensing of Blood banks
• 1998 : Professional donor banned
• 2001 : HCV testing made mandatory
• 2002 : National Blood Policy formulated
• 2008 : Blood Storage Centers
• 2009 : New Initiatives (Metro Blood Banks and plasma Fractionation Centre)
• 2014 : National Plasma Policy formulated
• 2016 : Baseline Assessment of all licensed Blood Banks in the Country
147
148
• NBTC is supported by a National Transfusion Services Core Coordination
Committee under chairpersonship of Director General of Health Services and a
Technical Resource Group under chairpersonship of Dr Neelam Marwaha, HOD,
Department of Transfusion Medicine, PGIMER, Chandigarh.
149
Assessment of NACO
Supported blood banks
A Preliminary Report 2016
150
151
Out of 1126, NACO supported blood banks
in the country, 1101 blood banks that
reported were considered
for analysis.
Maharashtra(120) had the highest number
of NACO supported blood banks followed
by Tamil Nadu (95), Uttar Pradesh
(89), Gujarat (77) and Karnataka (66)
http://naco.gov.in/national-blood-transfusion-council-nbtc-0
152
Availability of NACO supported BBs per 1,000,000 (1 million) population
http://naco.gov.in/national-blood-transfusion-council-nbtc-0
• Thirty-nine percent (427) of NACO supported blood banks had component
separation facility and the remaining 61% (674) blood banks did not have component
separation facility.
• Delhi -(95%) > Chandigarh (75%)>Maharashtra (71.6%)>Karnataka
(61.5%)>Gujarat (58.7%) >Kerala (57.8%).
• Odisha (9.6%)<Madhya Pradesh (16.1%)<Assam (19.2%) <Bihar (17.9%) <Tamil
Nadu (23.2%) <West Bengal (23.8%) <Rajasthan (25.5%) <Chhattisgarh (25%), and
Uttarakhand (27.8%)
• Andaman & Nicobar and Dadra Nagar Haveli had one each NACO supported blood
banks that had component separation facility
153
•
154
http://naco.gov.in/national-blood-transfusion-council-nbtc-0
155
http://naco.gov.in/national-blood-transfusion-council-nbtc-0
156
http://naco.gov.in/national-blood-transfusion-council-nbtc-0
RECENT DEVELOPMENT
• 2 Drug Regimen
• there is a focus on reducing short- and long-term toxicities of treatment while
maintaining robust efficacy.
• integrase inhibitor dolutegravir (DTG) and the nucleoside reverse transcriptase
inhibitor (NRTI) lamivudine (3TC)
• Chemistry-300 mg of lamivudine and 50 mg of dolutegravir (equivalent to 52.6 mg
dolutegravir sodium) as active ingredients.
• Inactive ingredients include povidone K29/32, sodium starch glycolate, sodium
stearyl fumarate magnesium stearate, mannitol and microcrystalline cellulose, as well
as hypromellose, polyethylene glycol, titanium dioxide in the tablet’s coat.
157
Zamora FJ, Dowers E, Yasin F, Ogbuagu O. Dolutegravir And Lamivudine Combination For The Treatment Of HIV-1
Infection. HIV AIDS (Auckl). 2019;11:255–263. Published 2019 Oct 23. doi:10.2147/HIV.S216067
• clinical trials have shown that the regimen works well forindividuals with high
viral loads (100,000–500,000 copies/mL) and low CD4 counts (<200 cells/mm3)
• Demerit-
• birth (neural tube) defects
• neuropsychiatric side effects including exacerbation of depressive disorders with
suicides
158
159
160
• A study of the second HIV patient to undergo successful stem cell transplantation
from donors with a HIV-resistant gene, finds that there was no active viral
infection in the patient's blood 30 months after they stopped anti-retroviral therapy,
according to a case report published in The Lancet HIV journal and presented at
CROI (Conference on Retroviruses and Opportunistic Infections).
• Date:March 10, 2020
• Source:The Lancet
161
RECENT DEVELOPMENT
162
https://www.who.int/hiv/hiv-apps/en/
COVID 19 AND HIV
• People living with HIV and on effective antiretroviral treatment (ART) are
currently not at an increased risk of getting coronavirus, or developing severe
symptoms.
• People living with HIV not on treatment or virally suppressed may be at a greater
risk.
163
https://www.avert.org/coronavirus/covid19-HIV
FUTURE
• Ending AIDS as a public health threat
by 2030.
• In 2015 the Millennium Development
Goals (MDGs) were replaced by 17
Sustainable Development Goals
(SDGs), each with specific targets to be
achieved by 2030
164
165
• SDG 3:
• Ensure healthy lives and promote wellbeing for all at all ages (including universal
access to HIV prevention services, sexual and reproductive health services and
drug dependence treatment and harm reduction services)
• TARGETS
• Target 3.3: end AIDS as a public health threat by 2030
• Target 3.8: achieve universal health coverage, access to quality health care services,
and access to safe, effective, quality, and affordable essential medicines and
vaccines for all.
166
https://sustainabledevelopment.un.org/?menu=1300
• SDG 4: Quality education, including targets on comprehensive sexual and
reproductive health (SRH) education and life skills
• SDG 5: Gender equality, including targets on sexual and reproductive health and
rights (SRHR) and the elimination of violence, harmful gender norms and practices
167
• SDG 10: Reduced inequalities,
including targets on protection against
discrimination, and the empowerment
of people to claim their rights and
enhance access to HIV services
• SDG 16: Peace, justice and strong
institutions, including reduced violence
against key populations and people
living with HIV.
168
SUMMARY
• HIV retrovirus icosahedral structure ,HIV 1 and HIV 2
• Globally, 37.9 million people living with HIV 23.3 million people were receiving
antiretroviral treatment in 2018
• HIV Life cycle occurs in six phases
• The three modes of transmission are sexual contact,blood or vertical transmission
• The various oral manifestations can be categorized into bacterial ,viral fungal
infections,neoplasms,immune mediated.
• The diagnosis of HIV can be done clinically by WHO clinical staging and
laboratory tests, ELISA and western blot test being the confirmatory test.
• Prevention can be achieved by creating awareness and treatment can be done by the
antiretroviral therapy.
• It has been targeted to end AIDS by 2030 through the sustainable development
goals 169
CONCLUSION
No effective cure currently exists for HIV. But with proper medical care, HIV can be
controlled. . If people with HIV take ART as prescribed, their viral load (amount of
HIV in their blood) can become undetectable. If it stays undetectable, they can live
long, healthy lives and have effectively no risk of transmitting HIV to an HIV-negative
partner through sex.
170
REFERENCES
• Park's Textbook of preventive and social medicine,25th edition,Bhanot Page-374-465
• Oxford Textbook of Global Public Health,6th edition ,Page-1124-1138
• Davidsons textbook of medicine
• Ananthanarayan and Paniker's Textbook of microbiology,8th edition,Universal press ,Page no578-579
• https://sustainabledevelopment.un.org/?menu=1300
• https://www.avert.org/coronavirus/covid19-HIV
• https://www.who.int/hiv/hiv-apps/en/
• Zamora FJ, Dowers E, Yasin F, Ogbuagu O. Dolutegravir And Lamivudine Combination For The Treatment Of
HIV-1 Infection. HIV AIDS (Auckl). 2019;11:255–263. Published 2019 Oct 23. doi:10.2147/HIV.S216067
• http://naco.gov.in/nacoevents/memorandum-understanding-mou-between-naco-and-department-internal-
security
• http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf
• Bajpai S, Pazare AR. Oral manifestations of HIV. Contemp Clin Dent. 2010;1(1):1–5. doi:10.4103/0976-
237X.62510
171
172

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AIDS and Its Oral Manifestation

  • 1. AIDS- Acquired Immunodeficiency Syndrome Presented by- Dr.Payal Dash 1st year Pg Trainee 1
  • 2. CONTENTS • Introduction • Background • HIV Virus • Etiopathogenesis • AIDS • Epidemiology -globally & India • Risk Factors • Modes of transmission • Oral Manifestations of HIV PART 1 2
  • 3. INTRODUCTION • What is HIV? • Who is an HIV positive person? • Persons who are HIV-positive are both infected and infectious for life. • Disease-Resulting from a pathophysiological response to external or internal factors. (Macilwaine SW. What is a Disease?. Br Med J. 1900;2(2085):1703–1704. ) • Disorder-A disruption of the disease to the normal or regular functions in the body or a part of the body. • Syndrome-A collection or set of signs and symptoms that characterise or suggest a particular disease.Calvo F, Karras BT, Phillips R, Kimball AM, Wolf F. Diagnoses, syndromes, and diseases: a knowledge representation problem. AMIA Annu Symp Proc. 2003;2003:802. 3
  • 4. BACKGROUND • HIV originated in Kinshasa, in the Democratic Republic of Congo around 1920 when HIV crossed species from chimpanzees to humans. • 1981- Pneumocystis carinii pneumonia (PCP) were found in five young, previously healthy gay men in Los Angeles. At the same time, there were reports of a group of men in New York and California with Kaposi’s Sarcoma • 1982-In September, the CDC used the term 'AIDS' (acquired immune deficiency syndrome) for the first time, describing it as • a disease at least moderately predictive of a defect in cell mediated immunity, occurring in a person with no known case for diminished resistance to that disease • 1983-In January 1983, AIDS was reported among the female partners of men who had the disease suggesting it could be passed on via heterosexual sex. • By the end of the year the number of AIDS cases in the USA had risen to 3,064 - of this number, 1,292 had died. 4
  • 5. • 1984-In April 1984, the National Cancer Institute announced they had found the cause of AIDS, the retrovirus HTLV-III. • 1985-In March 1985, the U.S Food and Drug Administration (FDA) licensed the first commercial blood test, ELISA, to detect antibodies to the virus. Blood banks began to screen the USA blood supply • 1986-May 1986, the International Committee on the Taxonomy of Viruses said that the virus that causes AIDS will officially be called HIV (human immunodeficiency virus) instead of HTLV-III/LAV. • 1987-In February 1987, the WHO launched The Global Program on AIDS to raise awareness; generate evidence-based policies • In March, the FDA approved the first antiretroviral drug, zidovudine (AZT), as treatment for HIV. • 1988- WHO declared 1st December as the first World AIDS Day. • 1989-In March 1989, 145 countries had reported 142,000 AIDS cases.USA-100000 5
  • 6. 6 1990 On 8 April 1990, Ryan White died of an AIDS-related illness aged 18 October, the FDA approved the use of zidovudine (AZT) to treat children with AIDS 1991 the Visual AIDS Artists Caucus launched the Red Ribbon Project to create a symbol of compassion for people living with HIV and their carers. The red ribbon became an international symbol of AIDS awareness. On 7 November, professional basketball player Earvin (Magic) Johnson announced he had HIV and retired from the sport A couple of weeks later, Freddie Mercury, lead singer of rock group Queen, announced he had AIDS and died a day later. 1992 Tennis star Arthur Ashe revealed he became infected with HIV as the result of a blood transfusion in 1983. In May, the FDA licensed a 10 minute testing kit which could be used by healthcare professionals to detect HIV-1
  • 7. 7 1993 an estimated 2.5 million AIDS cases globally 1994 In August 1994, the USA Public Health Service recommended the use of AZT to prevent the mother- to-child transmission of HIV. In December, the FDA approved an oral HIV test - the first non-blood HIV test. 1995 In June 1995, the FDA approved the first protease inhibitor beginning a new era of highly active antiretroviral treatment (HAART). immediate decline of between 60% and 80% in rates of AIDS-related deaths and hospitalisation in those countries which could afford it. 4.7 million new HIV infections - 2.5 million in southeast Asia and 1.9 million in sub-Saharan Africa. 1997 UNAIDS estimated that 30 million people had HIV worldwide equating to 16,000 new infections a day 1999 the WHO announced that AIDS was the fourth biggest cause of death worldwide and number one killer in Africa. An estimated 33 million people were living with HIV and 14 million people had died from AIDS since the start of the epidemic
  • 8. 8 2000 In September, the United Nations adopted the Millennium Development Goals which included a specific goal to reverse the spread of HIV, malaria and TB. 2001 In November, the World Trade Organization (WTO) announced the Doha Declaration which allowed developing countries to manufacture generic medications to combat public health crises like HIV. 2002 In November, the FDA approved the first rapid HIV test with 99.6% accuracy and a result in 20 minutes 2013 In 2013, UNAIDS reported that AIDS-related deaths had fallen 30% since their peak in 2005.91 An estimated 35 million people were living with HIV. 2017 For the first time ever, more than half of the global population living with HIV are receiving antiretroviral treatment, a record of 19.5 million people.
  • 9. • 2018- • Globally, 37.9 million people living with HIV • 23.3 million people were receiving antiretroviral treatment • 2019- • In June 2019, 24.5 million people were accessing antiretroviral therapy. • Between 2000 and 2018, new HIV infections fell by 37% and HIV-related deaths fell by 45%, with 13.6 million lives saved due to ART. 9
  • 10. HIV VIRUS • Human immunodeficency virus-double stranded RNA virus • Phylum: incertae sedis • Family: Retroviridae • Genus: Lentivirus • Class: incertae sedis • Order: Ortervirales • Subfamily: Orthoretrovirinae • Types of HIV -HIV 1 , HIV 2 10 SPECIES VIRULENCE INFECTIVITY Prevalence HIV 1 High High Global HIV 2 Low Low West Africa
  • 11. Types and Subtypes of HIV 11 HIV HIV 1 Group M A-L Group N Group O Group P HIV 2 Group A-H
  • 12. • HIV 1 • most common and pathogenic strain of the virus • major group (Group M) namely Group N, O and a group P. • With 'M' for "major", this is by far the most common type of HIV, with more than 90% of HIV/AIDS cases deriving from group M • M group is subdivided further into clades, called subtypes from A-L 12
  • 13. • Subtype A - eastern Africa. • Subtype B -Europe, the Americas, Japan, and Australia • Subtype C - Southern Africa, Eastern Africa, India, Nepal, and parts of China. • Subtype D - Eastern and central Africa • Subtype E - Southeast Asia • Subtype F - in central Africa, South America and Eastern Europe • Subtype G - in Africa and central Europe. • Subtype H - central Africa • Subtype J is primarily found in North, Central and West Africa, and the Caribbean • Subtype K and L is limited to the Democratic Republic of Congo (DRC) and Cameroon. 13
  • 14. • Group N • The 'N' stands for "non-M, non-O". • This group was discovered by a Franco-Cameroonia team in 1998 . • As of 2015, less than 20 Group N infections have been recorded. • Group O • The O ("Outlier") group has infected about 100,000 individuals located in West- Central Africa • Most common in Cameroon, 2% of HIV-positive samples were from Group O. 14
  • 15. • Group P • In 2009, a newly analyzed HIV sequence was reported to have greater similarity to a simian immunodeficiency virus recently discovered in wild gorillas • The virus had been isolated from a Cameroonian woman residing in France who was diagnosed with HIV-1 infection in 2004. 15
  • 16. • HIV 2 • The first case in the United States was in 1987. • As of 2010, there are 8 known HIV-2 groups (A to H). • Of these, only groups A and B are pandemic. • Group A is found mainly in West Africa, but has also spread globally to Angola, Mozambique, Brazil, India, Europe, and the US. • Group B is mainly confined to West Africa • HIV-2 is closely related to simian immunodeficiency virus endemic in sooty mangabeys (Cercocebus atys atys) (SIVsmm), a monkey species inhabiting the forests of Littoral West Africa. 16
  • 17. HIV STRUCTURE Lipid envelope receptor complex structural proteins enzymes RNA 17
  • 18. HIV STRUCTURE • spherical, 100 (90-120) nm in diameter. • lipid envelope, in which are embedded the trimeric transmembrane glycoprotein gp41 to which the surface glycoprotein gp120 is attached • matrix protein p17, • core proteins p24 and p6 • nucleocapsid protein p7 • lies 2 copies of the ~10 kilobase (kb) positive-sense, viral RNA genome (i.e. it has a diploid RNA genome), • protease, integrase and reverse transcriptase enzymes. 18
  • 19. HIV STRUCTURE • Viral Genes and antigens • 9 genes to code for the necessary proteins and enzymes. • principal genes are gag, pol, and env. • gag gene - core proteins. • pol gene- enzymes • env gene - glycoproteins. • rev, nef, vif, vpu, vpr, and tat—are important for viral replication and enhancing HIV’s infectivity rate. 19
  • 20. • Genes coding for structural proteins • participate in functional structure of virus • 1.gag gene(group specific antigen) • encodes for core and shell of virus • gene product is precursor protein p55 ,cleaved into p17(matrix protein),p24,p15 • The p24 (CA-capsid )protein forms the conical core of viral particles • p24 antigen(major core protein) can be detected in early stages in serum till the appearance of the antibodies 20
  • 21. • 2.pol gene • encodes reverse transcriptase ,protease and integrase • Pol has RNA-dependent and DNA-dependent polymerase activities. • expressed as precursor protein cleaved into p64,p51,p10,p32 • p64-reverse transcriptase and RNAse activity • p51-only reverse transcriptase activity • p10-protease,p32-integrase • RT is required to transcribe DNA from RNA template, and IN is necessary to integrate the double-stranded viral DNA into the host genome. 21
  • 22. • env gene(envelop) • determines synthesis of envelop gp160 that is cleaved into gp120 and gp41 • cleaved by a host protease, furin, within the endoplasmic reticulum of the host cell. • The post-translational processing produces a surface glycoprotein, gp120 , which attaches to the CD4 receptors present on lymphocytes, and gp41, which embeds in the viral envelope to enable the virus to attach to and fuse with target cells 22
  • 23. Essential regulatory proteins • tat (HIV trans-activator) • regulates the reverse transcription of viral genome RNA, ensuring efficient synthesis of viral mRNAs and regulating the release of virions from infected cells. • rev (regulator of expression of virion proteins): • The Rev protein binds to the viral genome via an arginine-rich RNA-binding motif that also acts as a NLS (nuclear localization signals), required for the transport of Rev to the nucleus from cytosol during viral replication. • Rev recognizes a complex stem-loop structure of the mRNA env located in the intron separating coding exon of Tat and Rev, known as the HIV Rev response element (RRE) 23
  • 24. Non structural and regulatory proteins • vif (viral infectivity factor gene) • important for the infectivity of HIV-1 virions depending on the cell type. HIV-1 has been found to require Vif to synthesize infectious viruses in lymphocytes, macrophages, and certain human cell lines. • vpr • important role in replication of the virus, specifically, nuclear import of the preintegration complex. • also arrest host cell cycle in the G2 phase. This arrest activates the host DNA repair machinery which may enable integration of the viral DNA. • HIV-2 encode an additional Vpr related protein called Vpx which functions in association with Vpr. • vpu (Virus protein U) - • specific to HIV-1 • involved in CD4 degradation 24
  • 25. Structure of RNA genome HIV 1 25
  • 26. ETIOPATHOGENESIS OF HIV • Immune system and central nervous system binding of virion to surface of target cell interaction with CXCR4 or CCR5 Membrane fusion and cellular entry involving gp41 Viral RNA reverse transcribed to ds DNA DNA transcribed to nucleus DNA used to transcribe new RNA 26
  • 27. ETIOPATHOGENESIS OF HIV • Enabled by 3 viral genes-GAG,POL ,ENV • 6 regulatory genes- VIF,VPR,VPU,NEF,TAT,REV • half life -1-2 hours in plasma,1.5 days in infected CD4 cells, 12 months in latently infected CD4 cells viral mRNA translated to viral peptide chains precursor polyproteins form new proteins and enzymes (viral protease) migrate to cell surface, cell lysis occurs. 27
  • 28. 28
  • 29. AIDS • Acquired immunodeficiency syndrome ( "slim disease") • caused by a retrovirus known as the human immunodeficiency virus (HIV) which breaks down the body's immune system • HIV 1(central africa) and HIV 2(west africa and india) known to cause AIDS • diagnosed when CD4 cell count falls below 200 cells/mm3 • immune system ceases and results in advanced HIV (<50cells/mm3) • When HIV infects a cell, it combines with that cell's genetic material and may lie inactive for years. Most people infected with HIV are still healthy and can live for years with no symptoms or only minor illnesses. They are infected with HIV, but they do not have AIDS. • without ART progression of HIV to death is 10-12 years 29
  • 30. CLINICAL FEATURES • The clinical features of HIV infection have been classified into four broad categories : • I. Initial infection with the virus and development of antibodies • II. Asymptomatic carrier state • Ill. AIDS-related complex (ARC) • IV. AIDS. 30
  • 31. • (I) INITIAL INFECTION • mild illness (fever. sore throat and rash) about 70 per cent of people • most HIV -infected people have no symptoms for the first five years • Once infected, people are infected for life. • HIV antibodies usually take between 2 to 12 weeks to appear in the blood-stream • The period before antibodies are produced is the "window period" during which, although the person is particularly infectious because of the high concentration of virus in the blood, he will test negative on the standard antibody blood test. • (II) ASYMPTOMATIC CARRIER STATE • Infected people have antibodies, but no overt signs of disease, except persistent generalized lymphadenopathy. 31
  • 32. • (III)AIDS RELATED COMPLEX • damage to the immune system, but no opportunistic infections • they may exhibit one or more of the following clinical signs; unexplained diarrhoea lasting longer than a month, fatigue , malaise, loss of more than 10 per cent body weight, fever, night sweats, or other milder opportunistic infections such as oral thrush,generalized lymphadenopathy or enlarged spleen. • Patients from high-risk groups who have two or more of these manifestations (typically including generalised lymphadenopathy), and who have a decreased number of T -helper lymphocytes are considered to have AIDS-related complex 32
  • 33. • (IV) AIDS • End- stage of HIV infection • Tuberculosis and Kaposi sarcoma • fungal infections such as Candida oesophagitis, Cryptococcus meningitis • parasitic infections such as Pneumocystis carinni pneumoni,or Toxoplasma gondii encephalitis when T-helper cell count has dropped to around 100. • cytomegaloviral retinitis • "slim disease". • AIDS encephalopathy or AIDS dementia 33
  • 34. • Signs and symptoms-Fever,fatigue, maculopapular rash,headache,weight loss, depression,night sweats,oral or genital ulcers • Acute infection -few days -more than 10 weeks 1993 revised classification system for hiv infection and expanded AIDS Survillience case definition for adoloscents and adults 34
  • 35. WORLD AIDS DAY • World AIDS Day takes place on 1 December each year. • It’s an opportunity for people worldwide to unite in the fight against HIV, to show support for people living with HIV, and to commemorate those who have died from an AIDS-related illness. • Founded in 1988, World AIDS Day was the first ever global health day. • THE RED RIBBON • universal symbol of awareness and support for people living with HIV. 35
  • 36. EPIDEMIOLOGY • The spread of HIV started at the beginning of the 20th century. • Zoonotic transmission of SIVcpz from chimpanzees (Pan troglodytes troglodytes) occurred for HIV-1 group M and group O around 1920 and for HIV-1 group N around 1960 in West Central Africa. • HIV-2 was transmitted zoonotically from sooty mangabey (Cercocebus atys) to human in West Africa around 1940. • Since the mid-1980s the different HIV-1 M subtypes have been spreading, leading to a global pandemic. In contrast to HIV-1, HIV-2 initially remained restricted to West Africa because of its significantly lower infectivity. • 35 million people were living with HIV in 2013 • The countries most affected by HIV with a high prevalence among 15- to 49-year-olds are Swaziland (approximately 27%), Lesotho (approximately 23%) and Botswana (approximately 23%). 36
  • 37. EPIDEMIOLOGY • Germany • From 2000 to around 2005 a significant increase of HIV infections was observed, with a plateau since 2006 • most affected group were MSM with about 75% (2,400/3,200) of the total number of new HIV infections in 2013. • The total number of 3,200 (95% CI 3,000–3,400) new infections was estimated for 2013 showing differences in the number of infections in different groups affected • The most affected group were men who have sex with men (MSM) with about 75% (2,400/3,200) of the total number of new HIV infections in 2013. Approximately 360 women (11.3%) and 190 men (5.9%) contracted an HIV infection by heterosexual contacts in Germany (hetero-domestic). 37
  • 38. • Europe • In 2012, approximately 30,000 new HIV diagnoses have been reported by 30 countries of the European Union (EU) and the European Economic Area (EEA) • Most diagnoses were reported in Lithuania, Estonia, Belgium, the UK and Luxembourg • In 2012, the ratio of men to women in the group of new infections was 3.2:1. • Since 2006 the percentage of newly diagnosed cases has been rather stable. However, infections for which the information ‘sexual contacts between men’ was provided have been increasing since 2006 by 11% to now 40.4%. The percentage of IVD with a newly diagnosed HIV infection has been decreasing over the same period by 7%. 38
  • 39. • Africa • Africa is the continent that is affected most by HIV infections. • About 25 million people in Africa live with HIV, about 22 million of whom in Sub- Saharan Africa . • The estimated HIV prevalence in Africa varies widely and lies between 0.1% in Egypt and Morocco and about 27% in Swaziland. • Heterosexual contacts are the main route of infection in Africa, and sex work and sexual violence contribute significantly to the spread of the disease. Approximately one third of those infected with HIV received antiretroviral therapy in 2013 • HIV prevalence in rural areas of Central Africa can be as low as a few ‰ and in urban areas can reach values of up to 30% . • HIV-1 M:C is the most prevalent subtype worldwide with a percentage of 30–36% of all subtypes 39
  • 40. • Australia • In Australia, the number of new HIV diagnoses has been increasing by approximately 26% since 2003 and has reached a value of 5.4/100,000 inhabitants in 2012. • The main mode of transmission is sexual contact among men . • In Australia, the most common subtype is HIV-1 M:B; several additional subtypes were imported mainly from Asia. • North America • About 50,000 new HIV diagnoses are reported annually in the USA with an estimated prevalence of 0.23% . • Approximately 1.1 million people live with HIV in the USA, 25% of whom are women. The main route of transmission is sexual contact between men. • About one third of all persons infected with HIV receive antiretroviral therapy 40
  • 41. • South America • In Latin America, approximately 1.3–1.9 million people are living with HIV. In Belize, Guyana and Suriname, the estimated HIV prevalence is above 1% . • Further recombinants are found in Brazil and in neighbouring countries • Two other recombinant strains of the subtypes B and F are circulating in Argentina 41
  • 42. • Asia • In Asia, about 1.7 million people are living with HIV, approximately 50% of whom receive antiretroviral therapy. • The number of newly diagnosed HIV infections has decreased from 2001 to 2012 • by about 26%. • With a generally low HIV prevalence in this region,Cambodia, China and India are the countries with the highest proportion of new HIV diagnoses. • The epidemic is concentrated in distinct groups with a high risk of exposure, such as MSM, sex workers, drug users and transsexuals . • In Asia, HIV prevalence reflects the contacts with Africa and North America. 42
  • 43. 43
  • 44. 44
  • 45. 45
  • 46. Prevalence of HIV in INDIA • National adult (15–49 years) HIV prevalence in India is estimated at 0.22% (0.16% – 0.30%) in 2017. • In 2017, adult HIV prevalence is estimated at 0.25%(0.18-0.34) among males and at 0.19% (0.14-0.25) among Females. • The adult HIV prevalence at national level has continued its steady decline from an estimated peak of 0.38% in 2001-03 through 0.34% in 2007, 0.28% in 2012 and 0.26% in 2015 to 0.22% in 2017. • Mizoram has shown the highest estimated adult HIV prevalence of 2.04%(1.57- 2.56), followed by Manipur (1.43%, 1.17-1.75), Nagaland (1.15%, 0.92-1.41), Telangana (0.70%, 0.50-0.95) and Andhra Pradesh (0.63%, 0.47-0.85). (India HIV Estimation 2017 report) 46
  • 47. • India is estimated to have had 22.67(10.92-40.60) thousand HIV positive women who gave birth in 2017. • State wise Prevention to Mother to child transmission (PMTCT) need were highest in Maharashtra (2.41 thousand) followed by Uttar Pradesh (2.29 thousands), Bihar, Andhra Pradesh, Karnataka, Telangana, West Bengal, Gujrat and Tamilnadu while least were Sikkim. • Since 2005, when the number of AIDS related deaths (ARD) started to show a declining trend, the annual number of AIDS related deaths has declined by almost 71%. In 2017 an estimated 69.11 (29.94 –140.84) thousand people died of AIDS- related causes nationally. • AIDS-related deaths have dropped in all of India’s States/UT with the exception of Assam, Bihar, Jharkhand, Haryana, Delhi, and Uttarakhand. 47
  • 48. • India- 3rd largest HIV epidemic • 88000 new HIV infections • 69000 AIDS- related death • 79 % aware of their status ,56% received antiretroviral treatment 48
  • 49. RISK FACTORS • Behaviours and conditions that put individuals at greater risk of contracting HIV include: • having unprotected anal or vaginal sex; • having another sexually transmitted infection (STI) • sharing contaminated needles, syringes and other injecting equipment and drug solutions when injecting drugs; • receiving unsafe injections, blood transfusions and tissue transplantation, and medical procedures that involve unsterile cutting or piercing; and • experiencing accidental needle stick injuries, including among health workers 49
  • 50. • Key population affected in INDIA - • Sex workers - • 2017, 1.6% female sex workers had HIV • Prevalence-7.4 % in Maharastra ,6.3 % in Andhra Pradesh • 91% reported they used condom • People who inject drugs • majorly in north eastern states 12.1 % in Manipur, 10% in Mizoram • Transgender people-- • 3.1%(2nd highest) • NACO reported 45% received interventions • Migrant workers-7.2 million migrant worker -0.2 % HIV • Truck drivers-0.2 % lived with HIV 50
  • 51. MODES OF TRANSMISSION • (a) Sexual transmission (man to man,heterosexual and oral) • (b) Parenteral(blood or blood product recipients,injection drug users,occupational injury) • (c) Vertical -Maternal- foetal transmission : mother-to child transmission • Exposure rate-90% for blood and blood products • 15-40%- vertical route • 0.5-1 %-injection drug use • 0.2-0.5%- genital mucus membrane spread • 0.1%-non genital mucus membrane spread • worldwide major route of transmission >75% is heterosexual • 5-10 percent -children during pregnancy birth or breastfeeding 51
  • 52. • SEXUAL CONTACT • AIDS is first and foremost a sexually transmitted disease. • Any vaginal, anal or oral sex can spread AIDS. Every single act of unprotected intercourse with an HIV- infected person exposes the uninfected partner to the risk of infection. • The size of the risk is affected by a number of factors, including the presence of STD, the sex and age of the uninfected partner, the type of sexual act, the stage of illness of the infected partner, and the virulence of the HIV strain involved. • women are more vulnerable to HIV infection . • Anal intercourse carries a higher risk of transmission than vaginal intercourse • For vaginal sex the risk is greater when woman is menstruating. • Exposed adolescent girls and women above 45 years of age are more prone to get HIV infection. • In teenagers the cervix is thought to be less efficient barrier to HIV than in mature genital tract of adult women. 52
  • 53. • An STD in either the HIV- negative or the HIV-positive partner facilitates the transmission of HIV. • The risk of transmission is 8-10 times higher. • As for HIV-infected people, they are more infectious to others in the very early stages, before antibody production i.e. during the "window period'', and when the infection is well advanced, because levels of virus in the blood at that time is higher than at other times. 53
  • 54. • Blood contact • AIDS is also transmitted by contaminated blood -transfusion of whole blood cells, platelets and factors VIII and IX derived from human plasma. • The risk of contracting HIV infection from transfusion of a unit of infected blood is estimated to be over 95 per cent. • Since the likelihood of HIV transmission through blood depends on the "dose" of virus injected, the risk of getting infected through a contaminated needle, syringe or any other skin- piercing instrument is very much lower than with transfusion. • needle- sharing by drug users is a major cause of AIDS in many countries, both developed and developing, and in some it is the predominant cause. • Any skin piercing (including injections, ear-piercing, tattooing, accupuncture or scarification) can transmit the virus, if the instruments used have not been sterilized and have previously been used on an infected person. 54
  • 55. • Maternal- foetal transmission : mother-to child transmission • HIV may pass from an infected mother to her foetus, through the placenta or to her infant during delivery or by breast-feeding. In the absence of any intervention, rates of this form of transmission can vary from 20- 25 per cent. • Transmission during the peripartum period accounts for one third to two-thirds of overall numbers infected • The risk of infection is higher if the mother is newly infected, or if she has already developed AIDS. HIV infected infants and children progress rapidly to AIDS. 55
  • 56. How HIV is not transmitted • shaking hands, hugging or kissing • coughing or sneezing • using a public phone • visiting a hospital • opening a door • sharing food, eating or drinking utensils • using drinking fountains • using toilets or showers • using public swimming pools • getting a mosquito or insect bite. 56
  • 57. Oral Manifestations of HIV • Oral manifestations of HIV infection occur in 30–80% of the affected patient population. • The various oral manifestations can be categorized into • Infections: bacterial, fungal, viral • Neoplasms: Kaposi's sarcoma, non-Hodgkin's lymphoma • Immune mediated: major aphthous, necrotizing stomatitis • Others: parotid diseases, nutritional, xerostomia • Oral manifestations as adverse effects of antiretroviral therapy. 57
  • 58. FUNGAL INFECTIONS • Candidiasis: • Oral or pharyngeal candidiasis are the commonest fungal infections observed as the initial manifestation of symptomatic HIV infection. • Many patients can have esophageal candidiasis as well. • It is usually observed at CD4 counts of less than 300/μl. • Candida albicans although nonalbicans species have also been reported. • erythematous candidiasis, pseudomembranous candidiasis, angular cheilitis, and hyperplastic or chronic candidiasis: 58
  • 59. • Erythematous candidiasis • presents as a red, flat, subtle lesion either • on the dorsal surface of the tongue and/or the hard/soft palates. • Patients complain of a burning sensation in the mouth more so while eating salty and spicy food. • Diagnosis is made on the basis of clinical examination, a potassium hydroxide preparation which demonstrates the fungal hyphae can be used for confirmation. • Pseudomembranous candidiasis • appears as creamy white curd-like plaques on the buccal mucosa, tongue, and other oral mucosal surfaces that can be wiped away, leaving a red or bleeding surface • extend to involve the oropharyx and esophagus 59
  • 60. • Angular cheilitis is erythema and/or fissuring and cracks of the corners of the mouth. Angular cheilitis can occur with or without the presence of erythematous candidiasis or pseudomembranous candidiasis. • Hyperplastic or chronic candidiasis presents as white nonremovable plaques over the mucosal surface; hence they cannot be scraped off. 60
  • 61. • Treatment of oral candidiasis depends on the clinical type, distribution, and severity of infection. • TOPICAL TREATMENT • Clotrimazole troches, nystatin pastilles, and nystatin oral suspension are effective for mild-to-moderate erythematous and pseudomembranous candidiasis. • Increased risk of caries can be avoided by using a nystatin oral suspension (100,000 units/5 ml, rinsing mouth, and expectorating 3 times/day). • Chlorhexidine 0.12% oral rinses do not contain a cariogenic substrate and may be similarly effective. • Topical amphotericin B can also be used in the treatment for resistant candidiasis and can be prepared by dissolving 50 mg in 500 ml of sterile saline (0.1 mg/ml). • Clotrimazole 1% cream, miconazole or ketoconazole 2% cream, and nystatin ointment are useful medications for angular cheilitis and for application to a removable denture base when there is candidal infection involving the underlying mucosa. 61
  • 62. • SYSTEMIC TREATMENT • imidazole (ketoconazole) and triazole (fluconazole and itraconazole) antifungal medications. • Fluconazole is given in the dose of 100–200 mg/day. • The duration of treatment with oral imidazoles usually is around 7–10 days but in cases of suspicion of esophageal involvement, the duration can be extended to 21 days. • As per the recent guidelines there is no role of prophylaxis for candidiasis in HIV patients. 62
  • 63. • 2.Histoplasmosis: • Granulomatous fungal disease caused by Histoplasma capsulatum. • The clinical presentation ranges from an asymptomatic or mild lung infection to an acute or chronic disseminated form. • Oral histoplasmosis appears as chronic ulcerated areas located on the dorsum of the tongue, palate, floor of the mouth, and vestibular mucosa. Focal or multiple sites can be involved. • In AIDS patients, histoplasmosis is rarely curable, but it can be controlled with long-term suppressive therapy consisting of the administration of amphotericin B and ketoconazole. 63
  • 64. • 3.Cryptococcosis: • Oral manifestations are quite unusual and only two cases have been reported in the literature. • The lesions consist of ulcerations of the oral mucosa, but the clinical diagnosis of oral cryptococcus may be difficult since other microbial infections and trauma may show similar appearances. Tissue biopsy may be required for the diagnosis and treatment involves use of amphotericin B. 64
  • 65. VIRAL INFECTIONS • 1.Oral hairy leukoplakia: • lateral surface of the tongue, extend to the dorsal and ventral surfaces • Lesions may be variably sized and may appear as vertical white striations,corrugations, or as flat plaques, or raised, shaggy plaques with hair-like keratin projections. • bilateral and asymptomatic. • Associated with a localized Epstein–Barr virus (EBV) infection and occurs most commonly in individuals whose CD4 lymphocyte count is less than 200/μl. • This condition usually does not require treatment but use of oral acyclovir, topical podophyllum resin, retinoids, and surgical removal have all been reported as successful treatments. 65
  • 66. • 2.Herpes simplex and varicella zoster virus infections: • Responsible for both primary and recurrent infections of the oral mucosa. • Oral manifestations, represented by diffuse mucosal ulcerations • Accompanied by fever, malaise, and cervical lymphadenopathy. • Ulcerations that follow the rupture of vesicles are painful • Recurrent HSV usually appears in keratinizing oral mucosa (i.e., palate, dorsum of tongue, and gingiva) as ulcerations but in most HIV-seropositive patients, this rule is not followed. • Contact with the varicella zoster virus (VZV) may result in varicella (chicken pox) as a primary infection and herpes zoster (shingles) as a reactivated infection. 66
  • 67. • 3.Cytomegalovirus • CMV-related oral ulcerations, are a recognized complication of HIV infection. • The diagnosis of oral CMV is based upon the presence of large intranuclear and smaller cytoplasmic CMV inclusions in the endothelial cells at the base of the ulcerations. • These infections usually manifest in stage IV of the infection when there is advanced immunosupression with a CD4 count below 50. • The drug of choice for CMV infection is intravenous gancyclovir. • 4.Human Papilloma Virus • Human papilloma virus (HPV) causes a focal epithelial and connective tissue hyperplasia, forming an oral wart. • In HIV-infected patients, oral HPV-related lesions have a papillomatous appearance, either pedunculated or sessile, and are mainly located on the palate, buccal mucosa, and labial commissure. 67
  • 68. Bacterial Infections • 1.Linear erythematous gingivitis: • This entity appears as a band of marginal gingival erythema, often with petechiae. • It is typically associated with no symptoms or only mild gingival bleeding and mild pain. • Histological examination fails to reveal any significant inflammatory response, • Oral rinsing with chlorhexidine gluconate often reduces or eliminates the erythema and may require prophylactic use to avoid recurrence. 68
  • 69. • 2.Necrotizing ulcerative periodontitis (NUP): • This periodontal lesion is characterized by generalized deep osseous pain, significant erythema ,spontaneous bleeding, and rapidly progressive destruction of the periodontal attachment and bone. • The destruction is progressive and can result in loss of the entire alveolar process in the involved area. • Patients also have severe halitosis. • More than 95% of patients with NUP have a CD4 lymphocyte count of less than 200/mm3. • Treatment consists of rinsing twice daily with chlorhexidine gluconate 0.12%, metronidazole (250 mg orally four times daily for 10 days), and periodontal debridement, which is done after antibiotic therapy has been initiated. 69
  • 70. • 3.Syphilis: • It is an uncommon cause of intraoral ulceration, even in HIV infection. • It is a chronic, nonhealing, deep, solitary ulceration; often clinically indistinguishable from that due to tuberculosis, deep fungal infection, or malignancy. • Combination treatment with penicillin, erythromycin, and tetracycline is the treatment of choice, the dosage and duration of the treatment depending on the presence or absence of neurosyphilis. 70
  • 71. NEOPLASMS • 1.Kaposi's sarcoma: • It is the most common intraoral malignancy associated with HIV infection. The lesion may appear as a red-purple macule, an ulcer, or as a nodule or mass. • KS is especially common among homosexual and bisexual males and is rarely found in HIV-infected women. • When only a few lesions exist and the lesions are small (< 1 cm), intralesional chemotherapy with vinblastine sulfate or sclerotherapy with 3% sodium tetradecyl sulfate is usually effective. 71
  • 72. • 2.Non-Hodgkin's lymphoma: • NHL is the most common lymphoma associated with HIV infection and is usually seen in late stages with CD4 lymphocyte counts of less than 100/mm3. • It appears as a rapidly enlarging mass, less commonly as an ulcer or plaque, and most commonly on the palate or gingivae. • A histological examination is essential for diagnosis and staging. • Prognosis is poor, with mean survival time of less than 1 year, despite treatment with multidrug chemotherapy. 72
  • 73. Immune mediated oral lesions • 1.Aphthous ulcers: • They are the most common immune-mediated HIV-related oral disorder, with a prevalence of approximately 2–3%. These ulcers are either large solitary or multiple, chronic, deep, and painful often lasting much longer in the seronegative population and are less responsive to therapy. • Treatment - topical steroid such as clobetesol when the lesions are accessible • dexamethasone oral rinse when not accessible. • Systemic glucocorticosteroid -prednisone 1 mg/kg • Alternative therapies such as dapsone 50–100 mg daily and thalidomide 200 mg daily for 4 weeks should be considered in recalcitrant cases. 73
  • 74. • 2.Xerostomia: • side effect of antiviral medications or other medications commonly , like angiolytics, antifungals, etc. • significant risk factor for caries and can lead to rapid dental deterioration. • lead to oral candidiasis, mucosal injury, and dysphagia, and is often associated with pain and reduced oral intake of food. • oral pilocarpine often provides improved salivary flow and consistency. 74
  • 75. Parotid Gland Disease • gland enlargement and diminished flow of secretions. • Histologically, there may be lymphoepithelial infiltration and benign cyst formation. • The enlargement typically involves the tail of the parotid gland or, less commonly, the submandibular gland, and it may present uni- or bilaterally with periods of increased or decreased size. • Occasional swelling can be managed simply by repeated aspiration and rarely is radical removal of the gland necessary. • The pathophysiological mechanism is not known, though cytomegalovirus has been suggested to play a role. 75
  • 76. 76
  • 77. • HIV prevalence going down in Odisha. The HIV prevalence is going down in Odisha. Compared to a HIV positive rate of 0.7 per cent in 2014-2015, around 0.3 per cent people in state are HIV positive in 2018-19. • 16,011 AIDS patients in Ganjam • 887 pregnant women are HIV positive in the district • Polasara block has 1,348 AIDS patients, the highest in the district • 12,195 AIDS patients are being given pension of Rs 500 per month • Srilanka eradicated both HIV and syphillis • CD4 Cells normal-500-1500 77
  • 78. Diagnosis of AIDS • Control of AIDS • HIV Survillience • NACO,NACP • National Blood Policy • Recent Developments • The future • Summary 78 PART 2
  • 79. Diagnosis of AIDS • CLINICAL • I. WHO case definition for AIDS surveillance • at least 2 of the following major signs are present in combination with at least 1 of the minor signs • Major signs 79 weight loss 10% of body weight chronic diarrhoea for more than 1 month prolonged fever for more than 1 month (intermittent or constant). persistent cough generalized pruritic dermatitis history of herpes zoster oropharyngeal candidiasis chronic progressive or disseminated herpes simplex infection generalized lymphadenopathy. Minor Signs
  • 80. CHILDREN • Major signs • weight loss or abnormally slow growth • chronic diarrhoea for more than 1 month • prolonged fever for more than 1 month. • Minor signs • generalized lymph node enlargement • oropharyngeal candidiasis • recurrent common infections, e.g. ear infection, • pharyngitis • persistent cough • generalized rash 80
  • 81. • II. Expanded WHO case definition for AIDS surveillance • For the purposes of AIDS surveillance an adult or adolescent ( > 12 years of age) is considered to have AIDS if a test for HIV antibody gives a positive result, and one or more of the following conditions are present : • less than 10% body weight loss • cryptococcal meningitis • pulmonary or extra- pulmonary tuberculosis • Kaposi sarcoma • neurological impairment • candidiasis of the oesophagus • recurrent episodes of pneumonia 81
  • 82. 82 WHO CLINICAL STAGING OF HIV INFECTION ADULTS CHILDREN CLINICAL STAGE 1 Asymptomatic Asymptomatic Persistent generalized lymphadenopathy Persistent generalized lymphadenopathy 82 Lymph nodes are larger than one centimetre in diameter, in two or more sites other than the groin area for a period of at least three months.
  • 83. 83 CLINICAL STAGE 2-ADULTS CHILDREN -Moderate unexplained weight loss (<10% of presumed or measured body weight) -Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media, pharyngitis) -Herpes zoster -Angular cheilitis -Recurrent oral ulceration -Papular pruritic eruption -Fungal nail infections -Seborrhoeic dermatitis -Unexplained persistent hepatosplenomegaly -Recurrent or chronic upper respiratory tract infections(otitis media, otorrhoea, sinusitis, tonsillitis) -Herpes zoster -Lineal gingival erythema -Recurrent oral ulceration -Papular pruritic eruption -Fungal nail infections -Extensive wart virus infection -Extensive molluscum contagiosum -Unexplained persistent parotid enlargement
  • 84. 84 CLINICAL STAGE III ADULTS CHILDREN Unexplained severe weight loss (>10% of presumed or measured body weight) Unexplained chronic diarrhoea for longer than 1 month Unexplained persistent fever (intermittent or constant for longer than 1 month) Persistent oral candidiasis Oral hairy leukoplakia Pulmonary tuberculosis Severe bacterial infections (such as pneumonia, empyema, pyomyositis, bone or joint infection, meningitis, bacteraemia) Unexplained moderate malnutritionb not adequately responding to standard therapy Unexplained persistent diarrhoea (14 days or more) Unexplained persistent fever (above 37.5°C, intermittent or constant, for longer than one 1 month) Persistent oral candidiasis (after first 6 weeks of life) Oral hairy leukoplakia Lymph node tuberculosis Pulmonary tuberculosis Severe recurrent bacterial pneumonia
  • 85. 85 CLINICAL STAGE III ADULTS CHILDREN Acute necrotizing ulcerative stomatitis,gingivitis or periodontitis Unexplained anaemia (<8 g/dl), neutropaenia (<0.5 x 109/l) and/or chronic thrombocytopaenia (<50 x 109/l) Acute necrotizing ulcerative gingivitis or periodontitis Unexplained anaemia (<8 g/dl), neutropaenia (<0.5 x 109/l) or chronic thrombocytopaenia (<50 x 109/l)
  • 86. 86 CLINICAL STAGING IV ADULTS CHILDREN HIV wasting syndrome Pneumocystis (jirovecii) pneumonia Recurrent severe bacterial pneumonia Chronic herpes simplex infection (orolabial, genital or anorectal of more than 1 month’s duration or visceral at any site) Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs) Extrapulmonary tuberculosis Kaposi sarcoma Cytomegalovirus infection (retinitis or infection of other organs) Unexplained severe wasting, stunting or severe malnutritiond not responding to standard therapy Pneumocystis (jirovecii) pneumonia Recurrent severe bacterial infections (such as empyema, pyomyositis, bone or joint infection, meningitis, but excluding pneumonia) Chronic herpes simplex infection (orolabial or cutaneous of more than 1 month’s duration or visceral at any site) Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
  • 87. 87 Extrapulmonary cryptococcosis, including meningitis Disseminated nontuberculous mycobacterial infection Progressive multifocal leukoencephalopathy Chronic cryptosporidiosis Chronic isosporiasis Disseminated mycosis (extrapulmonary histoplasmosis, coccidioidomycosis) Lymphoma (cerebral or B-cell non-Hodgkin) Symptomatic HIV-associated nephropathy or cardiomyopathy Recurrent septicaemia (including nontyphoidal Salmonella) Extrapulmonary tuberculosis Kaposi sarcoma Cytomegalovirus infection (retinitis or infection of other organs with onset at age more than 1 month) Central nervous system toxoplasmosis (after the neonatal period) HIV encephalopathy Extrapulmonary cryptococcosis, including meningitis Disseminated nontuberculous mycobacterial infection Progressive multifocal leukoencephalopathy Chronic cryptosporidiosis (with diarrhoea) Chronic isosporiasis Disseminated endemic mycosis (extrapulmonary histoplasmosis, coccidioidomycosis, penicilliosis)
  • 88. Laboratory Diagnosis • Screening tests • A person whose blood contains HIV antibodies is said to be HIV-positive, or seropositive, • screening test must be sensitive enough to identify all "true positives", • specific enough to record few "false positives". • The first kind of test is normally the ELISA. • The confirmatory test-Western Blot is a highly specific test • Virus isolation • Absolute CD4 cell count • CD4 Lymphocyte percentage • HIV Viral load tests • p24 antigen 88
  • 89. 89
  • 90. 90 Western blotting (protein blotting or immunoblotting) is a rapid and sensitive assay for detection and characterization of proteins. It is based on the principle of immunochromatography where proteins are separated into polyacrylamide gel according to their molecular weight
  • 91. CONTROL OF AIDS • Prevention • Antiretroviral treatment • specific prophylaxis • primary health care 91
  • 92. PREVENTION OF AIDS • Education • Combination of HIV Prevention- biomedical,behavioural and structural interventions • Male and female condom • needle syringe programme • opiod substitution therapy • voluntary medical male circumcision • Blood borne HIV transmission 92
  • 93. ANTIRETROVIRAL TREATMENT 93 Nucleoside reverse transcriptase inhibitors (NRTls) Nucleotide reverse transcriptas e inhibitors (NtRTls) Non-nucleoslde reverese transcriptase Inhibitors (NNRTls) Protease inhibitors (Pis) lntegrase strand transfer inhibitors (INSTls) Abacavir (ABC) Didanosine (ddl) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4T) Zidovudine (AZT) Tenofovir (TDF) Efavirenz (EFV) Etravirine (ETV) Nevirapine (NVP) Atazanavir + ritonavir (ATV/r) Darunavir + ritonavir (DRV)r) Fos-amprenavir + ritonavir (FPV/r) lndinavir + ritonavir (IDV/r) Lopinavir/rilona vir (LPV/r) Saquinavir + ritonavir (SQV/r) Raltegravir (RAL)
  • 94. WHO Recommended ARV treatment 1.When to start ART? 94 ( > 19 years old) All adults regardless of CD4 cells Priority- severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) and adults with a CD4 count ≥ 350 cells/mm3 . Pregnant and breastfeeding women All adults Adoloscents (10-19 years) all adolescents Priority - ART should be initiated in all adolescents with severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) and adolescents with a CD4 count ≥350 cells/mm3•
  • 95. • In children • all children infected with HIV below five years of age • Infants diagnosed in the first year of life • Children infected with HIV one year to less than five years of age • all children infected with HIV five years of age and older with CD4 cell count ≤500 cells/mm3, regardless of WHO clinical stage. • CD4 count ≤350 cells/mm3 95
  • 96. • Timing of ART for adults and children with TB • all TB patients living with HIV regardless of CD4 count. • TB treatment should be initiated first,followed by ART within the first 8 weeks of treatment. • CD4 counts less than 50 cells/mm3 should receive ART within the first two weeks of initiating 96
  • 97. • What to Start? • First-line ART for adults • consist of two nucleoside reversetranscriptase inhibitors (NRTIs) plus a non- nucleoside reverse-transcriptase inhibitor (NNRTI). • TDF + 3TC (or FTC) + EFV as a fixed-dose combination is recommended as the preferred option to initiate ART (strong recommendation, moderate-quality evidence). • If TDF + 3TC (or FTC) + EFV is contraindicated or not available, one of the following options is recommended: • AZT + 3TC + EFV • AZT + 3TC + NVP • TDF + 3TC (or FTC) + NVP 97
  • 98. • First-line ART for pregnant and breastfeeding women and their infants • fixed-dose combination of TDF + 3TC (or FTC) + EFV • Infants of mothers who are receiving ART and are breastfeeding should receive six weeks of infant prophylaxis with daily NVP. • If infants are receiving replacement feeding, they should be given four to six weeks of infant prophylaxis with daily NVP (or twice-daily AZT). • Infant prophylaxis should begin at birth or when HIV exposure is recognized postpartum 98
  • 99. • First-line ART for children 3 years of age and older (including adolescents) • EFV is the preferred NNRTI • NVP is the alternative • For children infected with HIV three years to less than 10 years old and adolescents weighing less than 35 kg • ABC + 3TC • AZT or TDF + 3TC (or FTC) • For adolescents infected with HIV (10 to 19 years old) weighing 35 kg or more, • TDF + 3TC (or FTC) • AZT + 3TC • ABC + 3TC 99
  • 100. • MONITORING THE RESPONSE TO ART AND DIAGNOSING TREATMENT FAILURE • 6months and 12 months • Viral load is recommended • CD4 count and clinical monitoring • Dried blood spot specimens using venous or capillary whole blood can be used to determine the HIV viral load. 100
  • 101. • In adults and adolescents (includes pregnant and breastfeeding women) • Second-line ART for adults should consist of two nucleoside reverse-transcriptase inhibitors (NRTIs) + a ritonavir-boosted protease inhibitor (PI). • The following sequence of second-line NRTI options is recommended: • After failure on a TDF + 3TC (or FTC) -based first-line regimen, use AZT + 3TC as the NRTI backbone in second-line regimens. • After failure on an AZT or d4T + 3TC-based first-line regimen, use TDF + 3TC (or FTC) as the NRTI backbone in second-line regimens. 101
  • 102. • In children (including adolescents) • After failure of a first-line NNRTI-based regimen, a boosted PI plus two NRTIs are recommended for second-line ART • LPV/r is the preferred boosted PI • After failure of a first-line LPV/r-based regimen, children younger than 3 years should remain on their first-line regimen • After failure of a first-line LPV/r-based regimen, children 3 years or older should switch to a second-line regimen • NNRTI plus two NRTIs • EFV is the preferred NNRTI 102
  • 103. • After failure of a first-line regimen of ABC or TDF + 3TC (or FTC), • Preferred- ART is AZT + 3TC • After failure of a first-line regimen containing AZT or d4T + 3TC (or FTC) • preferred - ART is ABC or TDF + 3TC (or FTC) • Third Line ART • National programme should develop policies for third-line ART. • Include new drug with minimal risk of cross-resistance to previously used regimens. such as INSTls and second-generation NNRTls and Pis. • Patients on a failing second-line regimen with no new ARV options should continue with a tolerated regimen. 103
  • 104. • Post-exposure prophylaxis (PEP) • consists of a comprehensive set of services • the short term (28 days) provision of antiretroviral drugs • ELIGIBILTY • ideally within 72 hours. • status of the source • Exposures • a. parenteral or mucous membrane exposure • b. bodily fluids • Exposures not requiring PEP • HIV positive • HIV negative 104
  • 105. 105 Post-exposure prophylaxis ARV regimens – adults and adolescents Doses of ARV drugs for HIV post-exposure prophylaxis for adults and adolescents
  • 106. 106 Post-exposure prophylaxis ARV regimens – children (≤10 years old) Prescribed frequency Adherence support
  • 108. • SPECIFIC PROPHYLAXIS • Primary prophylaxis against P carinii pneumonia should be offered to patients with CD4 count below 200 cells/µL. • The regimens available are trimethoprim sulfamethoxazole, aerosolized pentamidine and dapsone. • M. auium complex occurs in at least one-third of AIDS patients. • Rifabutin -Mauium intracelLulare with less than 200 CD4 cell/µL. • 300 mg Isoniazid- M. tuberculosis • Kaposi's sarcoma -interferon, chemotherapy or radiation. • Cytomegalovirus retinitis - ganciclovir, • cryptococcal meningitis - fluconazole • Esophageal candidiasis - fluconazole ,ketoconazole • Herpes simplex infection and herpes zoster - cyclovir or foscamet. 108
  • 109. HIV SURVILLIENCE The surveillance system would include:- (a) HIV Sentinel Surveillance (b) AIDS Case Surveillance (c) STDs Surveillance; and (d) Behavioral Surveillance. The types of HIV surveillance are : (a) HIV Seintinel Surveillance, (b) HIV Sero- Surveillance, (c) AIDS Case Surveillance, (d) STD Surveillance, (e) Behavioural Surveillance (f) Integration with surveillance of other diseases like tuberculosis etc. 109
  • 110. • The objectives of the surveillance are as follows : • 1. To determine the level of HIV infection among general population as well as high- risk groups in different states; • 2. To understand the trends of HIV epidemic among general population as well as high-risk groups in different states; • 3. To understand the geographical spread of HIV infection and to identify emerging pockets; • 4. To provide information for prioritization of programme resources and evaluation of programme impact; and • 5. To estimate HIV prevalence and HIV burden in the country. 110
  • 111. • HIV sentinel surveillance for HIV • 1994 in 55 sentinel sites ,1998-180 • The 14th HIV sentinel surveillance at ANC sentinel sites was implemented from 1st January 2015 to 31st March 2015 at 572 districts. Number of sentinel sites 111 Site type 2008-09 2010-11 2016-17 STD ANC ANC (rural) ANC (youth) IDU MSM FSW Migrant TG Truckers TB Fisher- folk/seamen 217 498 162 8 61 67 194 8 1 7 - - 184 506 182 8 79 96 262 20 3 20 - - 829 87 89 245 27 18 28
  • 112. 112
  • 113. • The 15th round of HSS • 2017 at 1323 sentinel sites- • 829 sites Antenatal Clinic (ANC) clinic attendees and • 494 sites among high-risk groups & bridge populations: Female Sex Workers (FSW),Men having Sex with Men (MSM), Injecting Drug Users (IDU), Hijra/Transgender People (H/TG), Single Male Migrants (SMM) & LongDistance Truckers (LDT). • 4.45 lakh blood specimens were tested across all population groups during the 15th round of HSS. • The highest prevalence recorded in the 2017 rounds of HSS was among IDU (6.26%, 95% CI: 5.92-6.59), followed by H/TG (3.14%, 95%CI:2.61-3.66), MSM (2.69, 95% CI: 2.47-2.91), FSW (1.56%, 95% CI: 1.46-1.66), LDT (0.86%, 95% CI: 0.64-1.07) and SMM (0.51%, 95% CI: 0.34-0.68). 113 http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf
  • 114. • Thirteen states have recorded an ANC HIV prevalence which is more than the national average. • Mizoram (1.19%), Nagaland (0.82%), Meghalaya (0.73%), Tripura (0.56%) • and Manipur (0.47%) were among the highest. • Gujarat and Andhra Pradesh HIV prevalence in the range of 0.41% to 0.44% among ANC clinic attendees • Overall 56 sentinel sites recorded HIV prevalence of > 1% • Bihar,Chhattisgarh, Delhi, Gujarat, Jharkhand, Odisha, Rajasthan and Uttar Pradesh. • Fourteen sites recorded an HIV prevalence of > 2% • Bihar, Chhattisgarh, Odisha, Rajasthan and Uttar Pradesh. 114 http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf
  • 115. • Of the 829 sentinel sites for ANC, 561 are consistent sites, and analysis of these sites indicates a declining trend at the national level. • The implementation of HSS in the FSW typology was completed at 245 sites across thirty-two states. Nine states recorded HIV prevalence of more than national average (1.56%, 95% CI: 1.46-1.66) while 17 sites recorded an HIV prevalence of >5% with a majority of them in Karnataka ,Maharashtra and Telangana • Among MSM, HSS was conducted at 89 sites across 26 states with thirteen sites recording prevalence of more than 5%. In total, 12 states recorded HIV prevalence of more than the national average (2.69, 95% CI:2.47-2.91) with more than 5% HIVprevalence in the states of Manipur(8.40%),Nagaland (7.66%) and Karnataka (5.40%). 115 http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf
  • 116. • The national HIV prevalence among the Injecting Drug Users was the highest among all population groups (6.26%, 95%CI: 5.92-6.59). • 87 sites spread across 26 states. • A total of nine states recorded an HIV prevalence of >5% • Mizoram (19.81%), Delhi (16.21%), Punjab (12.09%),Chhattisgarh (10.77%), West Bengal (10.76%), Uttarakhand (8.98%),Tripura (8.55%), Manipur (7.66%) and Madhya Pradesh (5.33%). • Thirty sites recorded HIV prevalence of >5%, with a majority of them in the states of Manipur, Punjab and Mizoram 116 http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf
  • 117. • A major expansion of H/TG sites was undertaken in this round of surveillance, with 18 sites participating in this round of HSS, • The HIV prevalence among this population group was the second highest (3.14%, 95%CI: 2.61-3.66) • The highest prevalence among H/TG was noted at 10.9% in the district of North East Delhi. Other than North East Delhi, t • prevalence of more than 5%: Kolkata (7.28%), Thane (6.80%) and Hyderabad (6.47%). 117 http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf
  • 118. • Counselling and HIV testing services • 1.Integrated Counselling and Testing Centres (ICTC). • 2. Prevention of parent-to-child transmission of HIV (PPTCT). • 3. HIV/tuberculosis collaborative activities. 118
  • 119. Level of HIV counselling and testing services 119 Community level Village level PHCs Sub district level civil hospitals State and district level HIV screening Standalone ICTCs and facility ICTCs Standalone ICTCs and facility ICTCs Standalone ICTCs
  • 120. • The essential package of PPTCT services in India are as follows : • 1. Routine offer of HIV counselling and testing to all pregnant women enrolled into antenatal care, with an 'opt out'option. • 2. Ensuring involvement of spouse and other family members, and move from an "ANC-Centric" to a "Family-Centric" approach. • 3 . Provision of life-long ART (TDF+3TC+EFV) to all pregnant and breast-feeding HIV infected women, regardless of CD4 count and clinical stage of HIVprogressic>n. • 4 . Promotion of institutional deliveries of all HIV infected pregnant women. • 5. Provision of care for associated conditions (STJ/RTI, TB and other opportunistic infections). 120
  • 121. • 6. Provision of nutrition, counselling and psychosocial support for HIV infected pregnant women. • 7. Provision of counselling and support for initiation of exclusive breast-feeds within an hour of delivery as the preferred option and continued for 6 months. • 8. Provision of ARV prophylaxis to infants from birth upto a minimum of 6 months. • 9. lntegrating follow-up of HIV-exposed infants into routine healthcarn services including immunization. 121
  • 122. • 10. Ensuring initiation of Co-trimoxazole Prophylactic Therapy (CPT) and Early Infant Diagnosis (EID) using HIV-DNA PCR at 6 weeks of age onwards, as per the EID guidelines. • 11. Strengthening community follow-up and outreach through local community networks to support HIVpositive pregnant women and their families. 122
  • 123. NATIONAL AIDS CONTROL PROGRAM • launched in the year 1987. • National AIDS Control Organization (NACO) -a separate wing to implement and closely monitor the various components of the programme. AIMS OF NACP • to prevent further transmission of HIV • to decrease morbidity and mortality associated with HIV infection • to minimize the socio-eonomic impact resulting from HIV infection. 123
  • 124. • MILESTONES OF NACO 124 YEAR MILESTONES 1986 -First case of HIV detected. - AIDS Task Force set up by the ICMR. - National AIDS Committee established under the Ministry of Health 1990 Medium Term Plan launched for four states and the four metros 1992 NACP-1 launched to slow down the spread of HIV infection. - National AIDS Control Board constituted. - NACO set-up. 1999 NACP- II begins, focussing on behaviour change, increased decentralization and NGO involvement. - State AIDS Control Societies established. 2002 -National AIDS Control Policy adopted. - National Blood Policy adopted. 2004 Anti retroviral treatment inititated
  • 125. 125 2006 National Council on AIDS constituted under chairmanship of the Prime Minister. - National Policy on Paediatric ART formulated. 2007 NACP-lll launched for 5 years (2007- 2012). 2014 NACP-IV launched for 5 years (2012-2017). 2017 National strategic plan for HIV/AIDS and STIs 2017-2024
  • 126. • NACP IV • goal of NACP-IV is to halt and reverse the epidemic in India over the next 5 years by integrating programmes for prevention, c.are, support and treatment. • The package of services under NACP-IV are as follows : • 1. Prevention services • 2.Care ,support and treatment services • COMPONENTS • Intensifying and Consolidating Prevention services with a focus on HRG and vulnerable populations • Expanding IEC services for (a) general population and (b) high risk groups with a focus on behavior change and demand generation • Comprehensive Care, Support and Treatment • Strengthening institutional capacities 126 http://naco.gov.in/nacp-iv-components
  • 127. NATIONAL AIDS CONTROL ORGANISATION • Division under ministry of health and family welfare 1992 • head-additional secretary • finance division-director-finance • admin and procurement -joint secretary 127 Joint secretary targeted interventions and laws basic services STI/RTI Management Blood safety lab services care support and treatment admin procrurement finance Additional secretary
  • 128. • Care,Support and treatment • 90-90-90 aims at ending AIDS by 2030 • 90% know their status • 90 %are on ART • 90 %have viral suspension • march 2017- 530 ART centres ,1108 link ART centres ,17centres of excellence,7 paediatric centres of excellence, 52'. ART Plus centres and 350 care and support centres 128
  • 129. Modes of treatment services 129 CoE & ART Plus ART centres Link ART centres and LAC plus centres Select medical colleges medical colleges and district level hospital sub district level hospitals and CHC
  • 130. • Services provided 1.first line ART 2.Second line ART 3.Third line ART 4.National paediatric HIV /AIDS initiative 5.Paediatric second line ART 6.Following up and monitoring 7.Managment of opportunistic infections 8.targeted interventions for high risk groups 9.link worker scheme 10.condom promotion 11.STD control programme 12.Pre-Packed STI/RTI Color coded kits 130
  • 131. National Strategic Plan and STI 2017-2024 131
  • 132. 132
  • 133. 133
  • 134. 134 The 15th Memorandum of Understanding (MoU) was signed between National AIDS Control Organization and Department of Internal Security on 1st September, 2017 at the Conference Hall, NACO a) Reach large number of Central Armed Police Forces with information on preventions and control of STI/HIV/AIDS; b) Facilitate building of humane perspective and appropriate skills among police force to reduce stigma and discrimination against PLHIV and MARPs, c) Integrate STI/ HIV/AIDS services in the medical and health services under the control of Department of Internal Security, Ministry of Home Affairs and d) Direct all forces under purview of Department of Internal Security to include the issue of HIV/AIDS in the training. http://naco.gov.in/nacoevents/memorandum-understanding-mou-between-naco-and-department-internal-security
  • 135. • Community Based Testing (CBT) in Rajasthan • RajasthanState AIDS Society (RSACS), inaugurated the first “Community Based Testing (CBT)”, facility in Indian Public Educational Society (IPES), TI Project, Bhilwara on 12th May’2017. 135 http://naco.gov.in/documentsreports
  • 136. 136 Red Ribbon Express'1 December 2007 Seven coaches carrying HIV prevention messages will traverse over 27,000 km making 180 halts, covering 166 districts across the country, reaching out to crores of people in over 50,000 villages for scaling up ground level mobilization activities. the government also announced provision of free 2nd line treatment in two centres of the country.Tambaram Hospital in Chennai and JJ Hospital in Mumbai http://naco.gov.in/press-release
  • 137. National Blood Policy,2002 • OBJECTIVES 1.To reiterate firmly the Govt. commitment to provide safe and adequate quantity of blood, blood components and blood products. • A national blood transfusion Programme shall be developed • Trading in blood i.e. Sale & purchase of blood shall be prohibited. • Transfusion Services shall be promoted • Necessary amendments shall be made in the Drugs & Cosmetics Act/Rules to provide special licenses to small garrison units. 137
  • 138. • 2.To make available adequate resources to develop and reorganise the blood transfusion services in the entire country. • National & State/UT Blood Transfusion Councils shall be supported/strengthened financially • Efforts shall be directed to make the blood transfusion service viable through non- profit recovery system 138
  • 139. • 3.To make latest technology available for operating the blood transfusion services and ensure its functioning in an updated manner. • Minimum standards for testing, processing and storage shall be set and ensured. • A Quality System Scheme shall be introduced • Regular proficiency testing of personnel shall be introduced in all the blood centres. • An External Quality Assessment Scheme (EQAS) approved by the National Blood Transfusion Council shall be introduced • Efforts shall be made towards indigenisation of kits, equipment and consumables used in blood banks. • Use of automation shall be encouraged • A mechanism for transfer of technology shall be developed • Each blood centre shall develop its own Standard Operating Procedures • Guidelines for Control' and disposal of biohazardous waste as per the provisions of the existing Biomedical Wastes (Management & Handling) Rules - 1996 under the Environmental Protection Act - 1986. 139
  • 140. • 4.To launch extensive awareness programmes for donorinformation, education, motivation, recruitment and retention in order to ensure adequate availability of safe blood. • Efforts shall be directed towards recruitment and retention of voluntary, non- remunerated blood donors • Enrolment of safe donors • State/UT Blood Transfusion Councils shall recognise the services of regular voluntary non-remunerated blood donors and donor organisers appropriately. • National/State/UT Blood Transfusion Councils shall develop and launch an IEC campaign • National / State / UT blood transfusion councils shall involve other departments / sectors for promoting voluntary blood donations 140
  • 141. • 5.To encourage appropriate clinical use of blood and blood products. • Blood shall be used only when necessary • National Guidelines on 'Clinical use of Blood' shall be made available and updated as required from time to time. • Effective and efficient clinical use of blood shall be promoted • Education and training in effective clinical use of blood shall be organised. • Blood and its components shall be prescribed only by a medical practitioner • Availability of blood components shall be ensured • Appropriate steps shall be taken to increase the availability of plasma fractions • Adequate facilities for transporting blood and blood products • Guidelines for management of blood supply during natural and man made disasters shall be made available 141
  • 142. • 6.To strengthen the manpower through Human Resource Development • Transfusion Medicine shall be treated as a speciality. • Transfusion Medicine shall be incorporated as one of the subjects. • In-service training programmes shall be organised for all categories • Appropriate modules for training of Donor Organisers/Donor Recruitment Officers shall be developed • Short orientation training cum advocacy programmes on donor motivation • Based Organisations(CBOs) and NGOs who wish to participate in Voluntary Blood Donor Recruitment Programme. • Inter-country and intra-country exchange for training and experience of personnel associated with blood centres • States/UTs shall create a separate cadre and opportunities for promotions 142
  • 143. • 7.To encourage Research & Development in the field of Transfusion Medicine and related technology. • A corpus of funds shall be made available to NBTC/SBTCs to facilitate research in transfusion medicine and technology related to blood banking. • A technical resource core group at national level shall be created to co-ordinate research and development in the country. • Multi-centric research initiatives on issues related to Blood Transfusion shall be encouraged. • To take appropriate decisions and/or introduction of policy initiatives on the basis of factual information • Computer based information and management systems shall be developed which can be used by all the centres regularly to facilitate networking 143
  • 144. • 8.To take adequate regulatory and legislative steps for monitoring and evaluation of blood transfusion services and to take steps to eliminate profiteering in blood banks • For grant/renewal of blood bank licenses • Fresh licenses to stand-alone blood banks in private sector shall not be granted. • A separate blood bank cell shall be created under a senior officer not below the rank of DDC(I) in the office of the DC(I) at the headquarter. • As a deterrent to paid blood donors who operate in the disguise of replacement donors, institutions who prescribe blood for transfusion shall be made responsible for procurement of blood for their patients through their affiliation with licensed blood centres. • States/UTs shall enact rules for registration of nursing homes wherein provisions for affiliation with a licensed blood bank for procurement of blood for their patients shall be incorporated. 144
  • 145. National Blood Transfusion Council (NBTC) • In accordance with the directive of the Supreme Court, NBTC was constituted in 1996 • Blood Transfusion Services have to ensure that Blood/ Components (Whole Blood/ Packed Red Cells/ Plasma/ Platelets) are • Available • Accessible • Affordable • Safe • Of standard quality 145
  • 146. OBJECTIVES OF NBTC • to promote voluntary blood donation, • ensure safe blood transfusion, • provide infrastructure to blood centres, • develop human resource and • formulate and implement the Blood Policy. 146
  • 147. MILESTONES OF BLOOD TRANSFUSION • 1945 : First blood bank in Kolkata • 1954 : Voluntary blood donation began. • 1975 : Blood bank licensing process started with HBV, Syphilis & Malaria • 1988 : HIV testing made mandatory • 1989 : MD Programme • 1992 : BTS under EMR division of DGHS • 1992 : NACO started and BTS shifted under NACO as BS Division • 1996 : Supreme court Judgement (PIL filed by common causes vs GoI) • 1996 : NBTC and SBTC formed • 1997 : Mandatory licensing of Blood banks • 1998 : Professional donor banned • 2001 : HCV testing made mandatory • 2002 : National Blood Policy formulated • 2008 : Blood Storage Centers • 2009 : New Initiatives (Metro Blood Banks and plasma Fractionation Centre) • 2014 : National Plasma Policy formulated • 2016 : Baseline Assessment of all licensed Blood Banks in the Country 147
  • 148. 148
  • 149. • NBTC is supported by a National Transfusion Services Core Coordination Committee under chairpersonship of Director General of Health Services and a Technical Resource Group under chairpersonship of Dr Neelam Marwaha, HOD, Department of Transfusion Medicine, PGIMER, Chandigarh. 149
  • 150. Assessment of NACO Supported blood banks A Preliminary Report 2016 150
  • 151. 151 Out of 1126, NACO supported blood banks in the country, 1101 blood banks that reported were considered for analysis. Maharashtra(120) had the highest number of NACO supported blood banks followed by Tamil Nadu (95), Uttar Pradesh (89), Gujarat (77) and Karnataka (66) http://naco.gov.in/national-blood-transfusion-council-nbtc-0
  • 152. 152 Availability of NACO supported BBs per 1,000,000 (1 million) population http://naco.gov.in/national-blood-transfusion-council-nbtc-0
  • 153. • Thirty-nine percent (427) of NACO supported blood banks had component separation facility and the remaining 61% (674) blood banks did not have component separation facility. • Delhi -(95%) > Chandigarh (75%)>Maharashtra (71.6%)>Karnataka (61.5%)>Gujarat (58.7%) >Kerala (57.8%). • Odisha (9.6%)<Madhya Pradesh (16.1%)<Assam (19.2%) <Bihar (17.9%) <Tamil Nadu (23.2%) <West Bengal (23.8%) <Rajasthan (25.5%) <Chhattisgarh (25%), and Uttarakhand (27.8%) • Andaman & Nicobar and Dadra Nagar Haveli had one each NACO supported blood banks that had component separation facility 153
  • 157. RECENT DEVELOPMENT • 2 Drug Regimen • there is a focus on reducing short- and long-term toxicities of treatment while maintaining robust efficacy. • integrase inhibitor dolutegravir (DTG) and the nucleoside reverse transcriptase inhibitor (NRTI) lamivudine (3TC) • Chemistry-300 mg of lamivudine and 50 mg of dolutegravir (equivalent to 52.6 mg dolutegravir sodium) as active ingredients. • Inactive ingredients include povidone K29/32, sodium starch glycolate, sodium stearyl fumarate magnesium stearate, mannitol and microcrystalline cellulose, as well as hypromellose, polyethylene glycol, titanium dioxide in the tablet’s coat. 157 Zamora FJ, Dowers E, Yasin F, Ogbuagu O. Dolutegravir And Lamivudine Combination For The Treatment Of HIV-1 Infection. HIV AIDS (Auckl). 2019;11:255–263. Published 2019 Oct 23. doi:10.2147/HIV.S216067
  • 158. • clinical trials have shown that the regimen works well forindividuals with high viral loads (100,000–500,000 copies/mL) and low CD4 counts (<200 cells/mm3) • Demerit- • birth (neural tube) defects • neuropsychiatric side effects including exacerbation of depressive disorders with suicides 158
  • 159. 159
  • 160. 160
  • 161. • A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections). • Date:March 10, 2020 • Source:The Lancet 161
  • 163. COVID 19 AND HIV • People living with HIV and on effective antiretroviral treatment (ART) are currently not at an increased risk of getting coronavirus, or developing severe symptoms. • People living with HIV not on treatment or virally suppressed may be at a greater risk. 163 https://www.avert.org/coronavirus/covid19-HIV
  • 164. FUTURE • Ending AIDS as a public health threat by 2030. • In 2015 the Millennium Development Goals (MDGs) were replaced by 17 Sustainable Development Goals (SDGs), each with specific targets to be achieved by 2030 164
  • 165. 165
  • 166. • SDG 3: • Ensure healthy lives and promote wellbeing for all at all ages (including universal access to HIV prevention services, sexual and reproductive health services and drug dependence treatment and harm reduction services) • TARGETS • Target 3.3: end AIDS as a public health threat by 2030 • Target 3.8: achieve universal health coverage, access to quality health care services, and access to safe, effective, quality, and affordable essential medicines and vaccines for all. 166 https://sustainabledevelopment.un.org/?menu=1300
  • 167. • SDG 4: Quality education, including targets on comprehensive sexual and reproductive health (SRH) education and life skills • SDG 5: Gender equality, including targets on sexual and reproductive health and rights (SRHR) and the elimination of violence, harmful gender norms and practices 167
  • 168. • SDG 10: Reduced inequalities, including targets on protection against discrimination, and the empowerment of people to claim their rights and enhance access to HIV services • SDG 16: Peace, justice and strong institutions, including reduced violence against key populations and people living with HIV. 168
  • 169. SUMMARY • HIV retrovirus icosahedral structure ,HIV 1 and HIV 2 • Globally, 37.9 million people living with HIV 23.3 million people were receiving antiretroviral treatment in 2018 • HIV Life cycle occurs in six phases • The three modes of transmission are sexual contact,blood or vertical transmission • The various oral manifestations can be categorized into bacterial ,viral fungal infections,neoplasms,immune mediated. • The diagnosis of HIV can be done clinically by WHO clinical staging and laboratory tests, ELISA and western blot test being the confirmatory test. • Prevention can be achieved by creating awareness and treatment can be done by the antiretroviral therapy. • It has been targeted to end AIDS by 2030 through the sustainable development goals 169
  • 170. CONCLUSION No effective cure currently exists for HIV. But with proper medical care, HIV can be controlled. . If people with HIV take ART as prescribed, their viral load (amount of HIV in their blood) can become undetectable. If it stays undetectable, they can live long, healthy lives and have effectively no risk of transmitting HIV to an HIV-negative partner through sex. 170
  • 171. REFERENCES • Park's Textbook of preventive and social medicine,25th edition,Bhanot Page-374-465 • Oxford Textbook of Global Public Health,6th edition ,Page-1124-1138 • Davidsons textbook of medicine • Ananthanarayan and Paniker's Textbook of microbiology,8th edition,Universal press ,Page no578-579 • https://sustainabledevelopment.un.org/?menu=1300 • https://www.avert.org/coronavirus/covid19-HIV • https://www.who.int/hiv/hiv-apps/en/ • Zamora FJ, Dowers E, Yasin F, Ogbuagu O. Dolutegravir And Lamivudine Combination For The Treatment Of HIV-1 Infection. HIV AIDS (Auckl). 2019;11:255–263. Published 2019 Oct 23. doi:10.2147/HIV.S216067 • http://naco.gov.in/nacoevents/memorandum-understanding-mou-between-naco-and-department-internal- security • http://naco.gov.in/sites/default/files/HIV%20SENTINEL%20SURVEILLANCE_06_12_2017_0.pdf • Bajpai S, Pazare AR. Oral manifestations of HIV. Contemp Clin Dent. 2010;1(1):1–5. doi:10.4103/0976- 237X.62510 171
  • 172. 172