HIV is a virus that weakens the immune system by destroying CD4 cells. It can lead to AIDS if not treated. The document discusses HIV/AIDS including definitions, epidemiology in India, risk factors, transmission methods, the virus life cycle, stages of infection, signs and symptoms, diagnosis, and treatment approaches. It provides an overview of HIV from introduction through various treatment strategies and guidelines in India.

1. H I V D i s e a s e
By
Bhukya Nom Kumar Naik (PharmD - Intern)

2. Welcome Message
Never stop
learning because,
life never stop
teaching. Bhukya Nom Kumar Naik – PharmD,
DAFE.
Vignan Pharmacy College,
Vadlamudi

3. PPT Contents
Introduction to HIV & AIDS.
Basic terminology and definitions.
Introduction and Definitions
Epidemiology in Indian scenario.
Basic introduction to Virus.
Epidemiology and Virus introduction
Major risk factors & Transmission methods.
Pathophysiology of Virus.
Risk Factors and Life cycle of virus
Various stages of HIV and
Signs and symptoms
Stages and clinical manifestations
Various methods of diagnosis and
Treatment and algorithm .
Diagnosis and Treatment
Question and answers.
Discussion
Cont…

4. Introduction and Definitions
H = Infects only Human beings.
I = Immunodeficiency virus weakens the immune system and increases the risk of infection.
V = Virus that attacks the body.
Human Immunodeficiency Virus
A = Acquired, not inherited.
I = Weakens the Immune system.
D = Creates a Deficiency of CD4+ cells in the immune system.
S = Syndrome, or a group of illnesses taking place at the same time.
Acquired Immune Deficiency Syndrome
Cont…

5. Cont…
 It is a lentivirus
 It belongs to family RETROVIRIDAE.
 There are 4 members of human retroviruses in 2 groups:
A. Transforming viruses: These are human T cell leukaemia lymphoma virus (HTLV) I and II
B. Cytopathic viruses: This group includes HIV–1 and HIV-2.

6. Cont…
A person infected with HIV is defined by the Centers for Disease Control and Prevention
(CDC) as having positive antibodies against HIV (positive HIV test), with 200 or more helper
T-lymphocytes (CD4 cell/mm3 ), and the absence of an AIDS-defining illness..
Human Immunodeficiency Virus
AIDS is a chronic, potentially life threatening condition caused by HIV and it is disease of the
immune system where lose of the body’s cellular immunity .
Acquired Immune Deficiency Syndrome

7. Cont…
Epidemiology and Virus introduction
 National adult (15–49 years) HIV prevalence
was estimated at 0.22% in 2020. and 0.23%
among males, and 0.20% among females.
 The national adult prevalence continued to
decline from an estimated peak level of
0.54% in 2000–2001 through 0.33% in
2010 to 0.22% in 2020.
 This corresponds to a 33.3% decline in the
last ten years. Similar consistent declines
were noted among both males and females
at the national level.

8. Cont…
 Among the States/UTs, in 2020, Mizoram had the highest estimated adult HIV prevalence of 2.37%,
followed by Nagaland (1.44%) and Manipur (1.15%), all of which were States in northeast India.
 Andhra Pradesh (0.66%), Meghalaya (0.53%), Telangana (0.48%) and Karnataka (0.45%) were the
other States with adult prevalence higher than 0.40%.
 Besides these States, Delhi, Maharashtra, Puducherry, Punjab, Goa and Tamil Nadu had an estimated
adult HIV prevalence greater than the national prevalence (0.22%).
 while Haryana and Chhattisgarh had an
estimated adult HIV prevalence in the
range of 0.20–0.21%.
 All other States/UTs in India had
estimated adult HIV prevalence below
0.20%.

9. Cont…
 Nationally, HIV incidence was estimated at 0.04 (0.02–0.09) per 1,000 uninfected
population in the calendar year 2020.
 It declined from 0.57 per 1,000 uninfected population in 1997 through 0.09–0.10 in
2009–10 to 0.04 in 2020, corresponding to a 56% decline in the last ten years

10. About HIV Virus
 In June 1981 five cases of Pneumocystis
jiroveci (formerly known as carinii)
pneumonia (PCP) were described in
homosexual men in Los Angeles, USA.
 In 1984 a new human retrovirus,
subsequently named human
immunodeficiency virus (HIV), was isolated
and identified as the cause of AIDS.
History
More Information…

11. Cont…
 HIV virus is spherical in shape.
 Range between 100 – 140 nm
 Contains an electron-dense core which is surrounded by a lipid membrane.

12. Cont…

13. Cont…
 The core contains:
a) Major capsid protein p24
b) Nucleocapsid proteins p7/p9
c) Two copies of genomic RNA
d) Three viral enzymes (protease, reverse transcriptase and integrase)
e) The viral core is surrounded by a matrix protein called p17.
f) The viral envelope is studded with two glycoproteins, gp120 and gp 41, critical for infection.
g) HIV proviral genome contains non-structural and regulatory genes like LTR, vif, vpr, vpu, nef and rev,
which code for different viral proteins.

14. Cont…
Risk Factors and Life cycle of virus
Behaviours and conditions that put individuals at greater risk of contracting HIV include :
 Having unprotected anal or Vaginal sex.
 Having another STDs such as Herpex, Syphilis and other STDs.
 Sharing contaminated Needles, Syringes and other injectable products.

15. Cont…
 Receiving unsafe Injections, Blood transfusion and tissue
transplantation or medical procedures which involves unsterile
cuttings.
 Experiencing accidental needle stick injuries among health
workers.
 Having multi sexual partners or extra marital affairs.

16. Cont…
The various stages of the life cycle of the HIV virus are :
1. Binding and Fusion (Post fusion effects)
2. Reverse Transcription
3. Integration (Binding, -3 processing, Standard transfer and GAP Repair)
4. Transcription
5. Assembly
6. Budding

17. Cont…

18. Cont…
The 2 major systems affected by HIV are : -
1 . Immune system and
2 . Central nervous system (CNS).
1. Immune system pathogenesis : - immune system is made up of T - cells (cell mediated
immunity) and B - cells (antigen - antibody mediated immunity).
 Entry of HIV into human body. CD4 acts as a receptor.
 HIV binds to CD4 cell through gp120 lipid protein .
 Fusion of HIV with T – cell occurs.
 HIV enters the membrane of T - cell. This process is known as INTERNALIZATION.

19. Cont…
 Release of viral DNA(Necessary of cell multiplication). Hence, by reverse transcription
process producess cDNA (a proviral DNA which helps in multiplication )
 A state of T - cell plays a major role for process of replication. if T - cell active then
replication occur.
 If T - cell is in crescent state then replication doesn't take place for many years.
 During division some of cDNA enters into T - cell and integrates into the post genome of T -
cell for budding .such type of infection is known as PRODUCTIVE INFECTION.
 Macrophages and monocytes are also infected by HIV.
 Infected macrophages found in tissues only and acts as resevoir for viral particle and their
transportation from one place to another place (macrophages are safe vehicles).

20. Cont…
2 .Central nervous system pathogenesis ; -
 After the attack of immune system , monocytes and macrophages are targeted.
 Viruses infect macrophages and microglia (HIV does not infect neurons).
 The HIV infected macrophages produce Cytokines which are highly toxic to the
neuronal cell

22. Cont…
Stages and clinical manifestations
Sl.no Classification of HIV – associated
with clinical disease
WHO Clinical stage
01 Asymptomatic 1
02 Mild 2
03 Advanced 3
04 Severe 4
WHO clinical staging of established HIV infection

23. Stage – 1 : Primary HIV infection, last for few weeks, Flu – like symptoms appear,
seroconversion take place and peripheral detection of HIV is HIGH.
Stage – 2 : Clinically asymptomatic, this state lasts about 10 years, High active lymph node
involvement is seen and glands are swollen. HIV antibodies are detected and peripheral
detection of HIV is LOW.
Stage – 3 : symptomatic, Immune system is severely damaged, Lymph nodes and tissue burnt
out, body fails to replace T – Helper cells, more pathogenic and multi system disease is seen.
Stage – 4 : HIV to AIDS

24. Stage – 1 Stage – 2
 Asymptomatic
 Persistent generalised lymphadenopathy
 Unexplained moderate weight loss (< 10% of
body weight)
 Recurrent upper respiratory tract infections
 Herpes zoster
 Angular cheilitis
 Recurrent oral ulceration
 Papular pruritic eruptions
 Seborrheic dermatitis
 Fungal nail infections

25. Stage – 3 Stage – 4
 Unexplained severe weight loss (> 10% of
body weight)
 Unexplained chronic diarrhoea for > 1
month
 Unexplained persistent fever (> 37.5°C for
> 1 month)
 Persistent oral candidiasis
 Oral hairy leucoplakia
 Pulmonary tuberculosis
 Severe bacterial infections
 Acute necrotising ulcerative stomatitis,
gingivitis or periodontitis
 Unexplained anaemia (< 80 g/L (8 g/dL)),
neutropenia (< 0.5 × 109 /L)
 and/or chronic thrombocytopenia (< 50 ×
109 /L)
 Candidiasis of oesophagus, trachea, bronchi or lungs
 Cervical carcinoma – invasive
 Cryptococcosis – extrapulmonary
 Cryptosporidiosis, chronic (> 1 month)
 Cytomegalovirus disease (outside liver, spleen and nodes)
 Herpes simplex chronic (> 1 month) ulcers or visceral
 HIV encephalopathy
 HIV wasting syndrome
 Cystoisosporiasis (formerly known as isosporiasis), chronic (> 1 month)
 Kaposi’s sarcoma
 Lymphoma (cerebral or B-cell non-Hodgkin)
 Mycobacterial infection, non-tuberculous, extrapulmonary or disseminated
 Mycosis – disseminated endemic (e.g. coccidioidomycosis, talaromycosis
(formerly penicilliosis), histoplasmosis)
 Pneumocystis pneumonia
 Pneumonia, recurrent bacterial
 Progressive multifocal leukoencephalopathy
 Toxoplasmosis – cerebral
 Tuberculosis – extrapulmonary (CDC includes pulmonary)
 Sepsis, recurrent (including non-typhoidal Salmonella) (CDC only includes
Salmonella)
 Symptomatic HIV-associated nephropathy*
 Symptomatic HIV-associated cardiomyopathy*
 Leishmaniasis, atypical disseminated*

26. Cont…
Stages and clinical manifestation's

27. Cont…

28. Commonly used screening tests are:
 Enzyme Linked Immunosorbent Assay (ELISA)
 Rapid tests
1. Immunoconcentration/Dot Blot assay (vertical flow)
2. Agglutination assay
3. Immunochromatographic assay (lateral flow)
4. Dipstick and comb assay based on Enzyme Immune Assay (EIA).
5. WB test
WB tests are a highly specific conformational test.
Diagnosis of Paediatric HIV Infection (< 18 months)
Nucleic Acid Testing (NAT)
Detection of Acute HIV Infection
Diagnosis and treatment

29. NATs include tests for the qualitative detection of HIV-1 DNA or RNA, as well as the
quantitative detection ofHIV-1 RNA(viral load determination)through various assays.
Qualitative Polymerase Chain Reaction for HIV DNA : Mostly used for 4 – 6 weeks infants
Qualitative Transcription-mediated Amplification Assay for HIV RNA :
Other Assays :
1. Virus Isolation and
2. Antigen Detection

30. The national programme follows:
1. Strategy I – Screening
2. Strategy II (A) – Surveillance purposes
3. Strategy II (B) – Diagnosis in symptomatic persons (the sample should be reactive with two different kits)
and
4. Strategy III – Diagnosis in asymptomatic persons (the sample should be reactive with three different kits).
The following strategies are to be used for HIV testing and diagnosis in adults and children above the age of 18
months:
• For Clinically Symptomatic persons: (Strategy II (B))
• For Clinically Asymptomatic persons: (Strategy III)
 ELISA/ Rapid tests (E/R) used in strategy I, II, & Ill
 Confirmatory tests with high specificity, like WBs and line immunoassays, are used in problem cases,
e.g., in cases of indeterminate/discordant result of E/R.

31. Strategy – 1 Strategy – 2 A

32. For indeterminate results, testing should be repeated on a second sample taken after 14-28
days.

33. For indeterminate results, testing should be repeated on a second sample taken after
14-28 days.

34. Classification of HIV
There are 2 types of Human Immunodeficiency Virus (HIV) viz. HIV type I (HIV-1) and HIV type
2 (HIV-2). HIV-2 is less pathogenic than HIV-1.

35. The ARV drugs Classification :
1. Block binding of HIV to the target cell (Fusion Inhibitors and CCR 5 co-receptor blockers)
2. Block the viral RNA cleavage and one that inhibits reverse transcriptase (Reverse Transcriptase
Inhibitors)
3. Block the enzyme integrase, which helps in the proviral DNA being incorporated into the host
cell chromosome (Integrase Inhibitors)
4. Block the RNA to prevent viral protein production
5. Block enzyme protease (Protease Inhibitors)
6. Inhibit the budding of virus from host cells.
Diagnosis and Treatment

37. Goals of ART
1. Clinical goals – Increased survival and improvement in quality of life
2. Virological goals – Greatest possible sustained reduction in viral load
3. Immunological goals – Immune reconstitution, that is both quantitative and
qualitative
4. Therapeutic goals – Rational sequencing of drugs in a manner that achieves clinical,
virological and immunological goals while maintaining future treatment options,
limiting drug toxicity and facilitating adherence
5. Preventive goals – Reduction of HIV transmission by suppression of viral load

38. Once the evaluation is completed, the key questions pertaining to ART are:
• When to start treatment?
• Which and how many agents to use? Choice of optimal regimen?
• How to monitor the therapy?
• How long to give therapy?
• When to change therapy and to what?
• Drug interactions involving antiretroviral therapy

39. 1st line ART
• The first-line ART essentially comprises of a NRTI backbone, preferably Non-Thymidine
(Tenofovir plus Lamivudine) and one NNRTI, preferably EFV.
• The patients with HIV-2 and both HIV-1 and HIV-2 co-infections need to be initiated on a PI
containing regimen, as NNRTIs (EFV/ NVP) are not active against HIV-2 virus.
2nd line ART
• A new class of ARV, a Ritonavir boosted PI (Atazanavir/ritonavir or Lopinavir/ritonavir)
• Supported by at least one new and unused NRTI (Zidovudine or Tenofovir) or in an inevitable
situation an integrase inhibitor (Raltegravir—presently)
• Continued Lamivudine administration ensures reduced viral fitness
3rd line ART
• Third-line regimens should include new drugs with minimal risk of cross-resistance to
previously used regimens such as Integrase strand transfer inhibitors (INSTIs) and second-
generation NNRTIs and PIs

40. Choice of First Line Regimen
 HIV – 1 : TENOFOVIR (TDF 300 mg) + LAMIVUDINE (3TC 300 mg) + EFAVIRENZ (EFV 600 mg)
(TLE) as fixed dose combination (FDC) in a single pill once a day.
 HIV – 2 (alone or combined with HIV -1) : tenofovir (300 mg) plus lamivudine (300 mg) plus
lopinavir/ Ritonavir (800/200 mg)

41. Choice of Second Line Regimen

42. Second-line ART recommendations for patients with HIV-1, failing to NNRTI based first- line ART

43. Second-line ART recommendations for patients with HIV-1, failing to PI based first line ART (Not
exposed to NNRTIs)

44. Second-line ART recommendations for patients with HIV-1, failing to PI based first line ART (intolerant to
NNRTIs or where NNRTIs cannot be used)

45. Second-line ART recommendations for patients with HIV-2, failing to PI (LPV/r) based first-line
ART

46. Raltegravir (400 mg) + Darunavir (600 mg) + Ritonavir (100 mg); one tablet each twice daily.
Choice of Third Line Regimen

47. Opportunistic Infections

49. Special Thanks
From Rxpharmedico