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Anti Retroviral Therapy
Dr . B.K. Shiva Kumar, MD
Medical Officer, ART Centre
JSS Hospital, Mysuru
FOCUS
 DIAGNOSIS OF HIV
 CLINICAL ASSESSMENT
 DRUGS, REGIMEN AND MONITORING
 PREGNANCY, INFANTS AND CHILDREN WITH HIV
 HIV-TB CO-INFECTION
 POST EXPOSURE PROPHYLAXIS
HUMAN IMMUNODEFICIENCY VIRUS
First ever known case of HIV infection was diagnosed in June 1981 in Los Angeles, USA.
In India, first detected among female sex workers screened for HIV at Chennai in 1986.
In Karnataka, at Saudatti in Belgavi district (Devadasi Rituals) in 1987.
HIV infection is now considered a chronic manageable disease and majority of the
PLHIV remain healthy if correct and timely treatment is started.
Prevalence:
As per India HIV estimation report 2020, HIV prevalence was estimated at 0.22%
(0.24% among males; 0.20% among females).
The prevalence continued to decline
0.54% in 2001
0.33% in 2010
0.22% in 2020 0.21% in 2021 ………………..24.01 Lakhs (Third Highest in World)
Modes of
Transmission
At Risk Population !
a) Sex workers
b) Truckers
c) Migrants
d) Trans-genders
e) IV drug abusers
1. Sexual:
a) Heterosexual
b) MSM
2. Blood transfusion
3. Mother to child
4. Injection drug abuse
5. Needle stick injury,
blood and body fluids splash.
NATIONAL AIDS CONTROL
ORGANIZATION(NACO)
Policies for prevention and control of HIV infection
 NACP-I started in 1992 and lasted until 1999.
 NACP-II (2000–2005)
 NACP-III (2006-2011)
 NACP-IV (2012–2017)------( extended till March 2021).
 NACP-V (2021-2026)
95% of the estimated PLHIV know their status, of which
95% PLHIV are on ART, of which
95% PLHIV have viral suppression
In the current phase of NACP-V (2021–2026),
the focus is on ensuring PLHIV survive longer and
lead productive lives. This will be achieved through
improving retention in HIV care and adherence to
ART through a client-centric approach to providing
care, support and treatment services.
The current strategic plan aims to achieve:
• zero new infections
• zero AIDS-related deaths
• zero discrimination
for paving the way for an end of AIDS as a public health threat by 2030.
NACO
• NATIONAL
SACS (KSAPS)
• STATE
ART CENTRE
• DISTRICT
LINK ART
• TALUK
SOCH: Strengthening Overall Care for HIV beneficiaries
Consent
Confidentiality
Counselling
• Pre test
counselling
• Post test
counselling
Integrated Counselling and Testing Centre (ICTC)
Diagnosis of HIV
In adults and children > 18 months:
In infants and children < 18 months:
Rapid tests (Sensitivity of >99.5 %
and Specificity of >98 %)
Total Nucleic Acid PCR test on a
Dried Blood Spot
Window period
Window period: the period between infection with HIV and the time
when HIV antibodies can be detected in the blood (6–12 weeks).
A blood test performed during the window period may yield
a negative test result for HIV antibodies.
Maternal antibodies to HIV, transferred passively to the infant during pregnancy
Usually persist for nearly 9–12 months in the infant.
In some children, they may persist for as long as 18 months.
Maternal antibodies
Features of HIV-2
Less pathogenic and slower progression of disease
Longer asymptomatic stage and lower viral loads
Slower decline in CD4 counts
Lower rates of vertical transmission
• Patients with dual infection (HIV-1 and HIV-2) tend
to present at a more advanced stage of the disease.
• Infection with both HIV-1 and HIV-2 generally carries
the same prognosis as that of HIV-1 single infection.
Types of
HIV Virus
Goals of ART
Clinical goal
•Increased
survival and
improvement in
quality of life
Virological
goal
•Greatest
possible
sustained
reduction in
viral load
Immunological
goal
•Immune
reconstitution
i.e, quantitative
increase in CD4
Therapeutic
goal
•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
Preventive
goal
•Reduction of
HIV transmission
by suppression
of viral load
Scope of services
Pregnancy and HIV
Patients with HIV
HIV TB co-infection
Infants and
Children
with HIV
Infants and Children with HIV
Post Exposure Prophylaxis
Patient Registration
Rapid initiation of ART within 7 days from diagnosis
ART Number allotted, once the ART is started
Green book (details of the treatment will be entered, to be brought during
each visit)
White Card (demographic details, clinical parameters, lab values and
details of treatment)
Each patient will be given a Pre- ART number
Address proof, Aadhaar card and 2 photos
Patients should have ICTC report
Clinical Assessment
Once the PLHIV are enrolled in
an ART centre, a comprehensive
clinical assessment should be done
to obtain baseline clinical status and
to rule out OIs.
Medical History
 4 symptom screening for TB :
Adults: fever, cough, weight loss, night sweats;
Children: fever, cough, poor weight gain, h/o contact with a TB case
 Persistent symptoms – headache, poor concentration, seizures;
 Medical history for comorbid conditions like Diabetes and Hypertension;
 History of tuberculosis;
 Prior exposure to ARVs in the past;
 History of STI;
 HIV risk behaviour – multiple partners, key populations, injecting drug use;
 Substance abuse – alcohol, tobacco, oral or injecting drugs;
 Allergies/medication/vaccines;
 Pregnancy and contraception.
Physical Examination
Appearance: pallor, icterus, orientation, wasting
Vital signs: height, weight, temperature, blood pressure
Skin: herpes simplex, herpes zoster, PPE
Lymph nodes: cervical, axillary and inguinal
Mouth: oral candidiasis, oral hairy leukoplakia
Chest: congestion, consolidation
Abdomen: hepato-spenomegaly, tenderness
Neurological: comprehensive
Eyes: fundus examination if CD4 < 100 cells/cu mm.
Anogenital : genital lesions, urethral or vaginal discharge
Laboratory
monitoring
Baseline Investigations
 Haemogram/CBC
 Fasting blood sugar
 Blood urea, serum creatinine
 LFT
 Lipid profile
 VDRL
 HBsAg
 HCV
 Serum cryptococcal antigen
 CD4 count
 Urine for routine and microscopy
 X-ray Chest
 USG Abdomen
 CBNAAT
WHO Clinical Staging - Stage I
• Asymptomatic
• Persistent generalized
lymphadenopathy
• Asymptomatic
• Persistent generalized
lymphadenopathy
 Adults and adolescents  Children
WHO Clinical Staging -Stage II
 Children
• Unexplained hepato-splenomegaly
• Recurrent respiratory tract infections
(Otitis Media, Sinusitis, Tonsillitis)
• Herpes zoster
• Lineal gingival erythema
• Recurrent oral ulceration
• Papular pruritic eruption
• Fungal nail infections
• Extensive wart virus infection
• Extensive Molluscum contagiosum
• Persistent parotid enlargement
 Adults and adolescents
• 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 severe weight loss (>10% of
the presumed or measured body weight)
• Chronic diarrhoea for more than 1 month
• 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)
• Acute necrotizing ulcerative stomatitis,
gingivitis or Periodontitis
• Unexplained anaemia (Hb < 8 g/dl )
• Unexplained moderate malnutrition not
responding to standard therapy
• Chronic diarrhoea (14 days or more)
• Persistent fever (intermittent or constant,
for longer than 1 month)
• Persistent Oral Candidiasis (after the first
6 weeks of life)
• Oral Hairy Leukoplakia
• Lymph node Tuberculosis
• Pulmonary Tuberculosis
• Severe recurrent bacterial Pneumonia
• Acute necrotizing ulcerative stomatitis,
gingivitis or Periodontitis
• Unexplained anaemia (Hb < 8 gm/dl)
 Adults and adolescents  Children
WHO Clinical Staging - Stage III
 Children
• Unexplained severe wasting, stunting or
severe malnutrition not responding to
standard therapy
• Pneumocystis (jiroveci) 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 duration
or visceral at any site)
• Oesophageal Candidiasis (or Candidiasis of
• trachea, bronchi, or lungs)
• Extra pulmonary Tuberculosis
• Kaposi’s sarcoma
• Cytomegalovirus infection (retinitis or
infection of other organs with onset at age >
1 month)
 Adults and adolescents
• HIV wasting syndrome
• Pneumocystis (jiroveci) Pneumonia
• Recurrent severe bacterial Pneumonia
• Chronic Herpes Simplex infection (orolabial,
genital or anorectal of more than 1 month
duration or visceral at any site)
• Oesophageal Candidiasis (or Candidiasis of
trachea, bronchi or lungs)
• Extra pulmonary Tuberculosis
• Kaposi’s sarcoma
• Cytomegalovirus infection (retinitis or infection
of other organs)
• Central nervous system Toxoplasmosis
• HIV encephalopathy
• Extra pulmonary Cryptococcosis, including
Meningitis
WHO Clinical Staging - Stage IV
 Children
• Central nervous system Toxoplasmosis (after
the neonatal period)
• HIV encephalopathy
• Extra pulmonary Cryptococcosis, including
Meningitis
• Disseminated nontuberculous mycobacterial
infection (NTM)
• Progressive Multifocal Leukoencephalopathy
• Chronic Cryptosporidiosis (with diarrhoea)
• Chronic Isosporiasis
• Disseminated mycosis (extra pulmonary
Histoplasmosis, Coccidioidomycosis,
Penicilliosis)
• Cerebral or B-cell non-Hodgkin’s Lymphoma
• HIV-associated nephropathy or
cardiomyopathy
 Adults and adolescents
• Disseminated non-tuberculous mycobacterial
infection (NTM)
• Progressive Multifocal Leukoencephalopathy
(PML)
• Chronic Cryptosporidiosis
• Chronic Isosporiasis
• Disseminated mycosis (extra pulmonary
Histoplasmosis, Coccidioidomycosis)
• Lymphoma (cerebral or B-cell nonHodgkin’s)
• HIV-associated nephropathy or cardiomyopathy
• Recurrent septicaemia (including nontyphoidal
Salmonella)
• Invasive cervical carcinoma
• Atypical disseminated leishmaniasis
WHO Clinical Staging - Stage IV ......cont’d...
Association between CD4 and opportunistic infections
Management of OI’s before ART initiation
Clinical Picture Action
Tuberculosis
ART should be started as soon as possible
within 2 weeks of initiating TB treatment,
regardless of CD4 cell count
Pneumocystis pneumonia (PCP)
Treat PCP first; start ART when PCP
treatment is completed
Oesophageal candidiasis
Cryptococcal meningitis
Treat oesophageal candidiasis first;
start ART as soon as the patient can swallow
Cytomegalovirus Retinitis Treat CMV urgently; start ART after 2 weeks
Toxoplasmosis Treat Toxoplasmosis; start ART after 6 weeks
Treat cryptococcal meningitis, start ART after
4-6 weeks when the patient is stabilized
HIV life cycle andARV targets
ART DRUGS
ENTRY INHIBITORS :
• HIV enters CD4 cells via CD4 receptor in conjugation with one of its
co-receptors – CCR5 & CXCR4.
• CCR5 Antagonist – MARAVIROC– used only in treatment experienced
patients with drug resistant virus.
• FUSION inhibitors – ENFUVIRTIDE – bind to GP41 (envelope protein of HIV)
and prevent their fusion with T-cell.
• ATTACHMENT inhibitor – FOSTEMSAVIR – approved in 2020 that bind to
GP120 (envelope protein of HIV) and prevent HIV fusion with CD4 T cell.
REVERSE TRANSCRIPTASE
INHIBITORS:
A. Nucleotide Reverse Transcriptase Inhibitors (NtRTI)
• TENOFOVIR* – Alafenamide (TAF) & Disoproxil fumarate (TDF)*
B. Nucleoside Reverse Transcriptase Inhibitors (NRTI)
• ABACAVIR (ABC) *
• LAMIVUDINE (3TC) *
• ZIDOVUDINE (AZT)*
• EMTRICITABINE (FTC)
• DIDANOSINE (ddi)
• STAVUDINE (d4T)
C. Non- Nucleoside Reverse Transcriptase Inhibitors (NNRTI)
• NEVIRAPINE (NVP) *
• EFAVIRENZ (EFV) *
• DELAVIRIDINE
• RILPIVIRINE
• ETRAVIRINE
INTEGRASE INHIBITORS:
• DOLUTEGRAVIR (DTG) *
• RALTEGRAVIR (RGV) *
• ELVITEGRAVIR
• BICTEGRAVIR
• CABOTEGRAVIR
PROTEASE INHIBITORS:
• RITONAVIR (RTV) *
• LOPINAVIR (LPV) *
• ATAZANAVIR (ATV) *
• DARUNAVIR (DRV) *
• SAQUINAVIR
• NELFINAVIR
• INDINAVIR
• AMPRENAVIR
Optimal Regimen
Based on the evidence supporting better efficacy and fewer side effects, the preferred
first-line ART regimen for PLHIV is as follows:
Age > 10 yrs and weight > 30 kg Tenofovir(300mg) + Lamivudine (300 mg) +
Dolutegravir(DTG 50 mg)
TLD regimen as FDC in a single pill once daily
PLHIV with body weight < 30 kg ABC (600 mg) + Lamivudine (300mg)+ DTG (50 mg)
ABC (600 mg OD) + Lamivudine (as per creatinine
clearance**) and DTG (50 mg)
All patients with high serum
Creatinine Values(above ULN)
PLHIV on Rifampicin-containing
ATT regimen
TLD + additional dose of DTG 50 mg (12 hours
after taking their regular dose) until 2 weeks after
completion of ATT
Monitoring and follow up
Patients are advised to visit ART regularly every month
Body weight (Height in children)
Treatment Adherence
4-Symptom TB screening
Screening for HTN, Diabetes
Every visit
Every visit
Every visit
Every visit
Lab Investigations:
Hb, RBS, SGOT, SGPT, Urea, Creatinine Every 6 Months
CD4 count:
• CD4 must be done every 6 months, can be discontinued if it reaches > 350 cells/mm3
and viral load is < 1000 copies/ml (when both tests are conducted at the same time).
Viral load:
• Viral load at 6 months, 12 months and then every 12 months
• For patients on second/third-line ART, Viral Load testing to be done every 6 months
Advanced HIV Disease: PLHIV with advanced HIV disease are defined as
presenting with CD4 count < 200 cells/cu.mm. or WHO clinical stage 3 or 4
or children aged < 5 years
Expected response to ART
• Virological response to ART: The plasma viral load done 6 months after
initiation of ART should come down to<1000 copies/ml and should be
maintained at undetectable or <1000 copies/ ml throughout the treatment course
• Immunological response to ART: is defined as an increase of at least 50 CD4
cells/mm3 at 6 months of ART. This increase is usually 50–100 cells/mm3 within
6–12 months of ART initiation in ARV-naive patients, who are fully adherent to ART
• Clinical response to ART: Clinical monitoring should include evaluation of
weight, general well-being (functional status), adverse reaction to drugs and
keeping an eye out for IRIS, especially in patients with low CD4 count
IRIS
Immune Reconstitution Inflammatory Syndrome
The worsening of signs and symptoms due to known infections, or the development of disease due
to occult infections within 6 weeks to 6 months after initiating ART, with an increase in CD4 count.
IRIS should be diagnosed by excluding the following;
a) Active OI, b) Treatment failure, c) Side effect from ARV, d) Failure to antimicrobial therapy
The most serious and life-threatening forms of paradoxical IRIS are TB and Cryptococcosis.
Important steps to reduce the development of IRIS include;
• Earlier HIV diagnosis and initiation of ART before decline of CD4 below 200 cells/mm3
• Improved screening for OIs before ART, especially TB, Cryptococcus, CMV and
optimal management of OIs before initiating ART.
IRIS is generally self-limiting and interruption of ART is rarely indicated
Anti microbial therapy is required to reduce and eliminate triggering pathogen
Short-term therapy with corticosteroids or non-steroidal anti-inflammatory drugs
Temporary cessation of ART must be considered, only in potentially life-threatening forms of IRIS
Risk factors for IRIS: 1) People with CD4 counts below 100 cells/cu mm at ART initiation
2) People with rapid initial fall in HIV viral load due to therapy
3) Shorter interval between OI therapy initiation and ART initiation
4) Higher HIV RNA at ART initiation
Adverse drug effects of ARVs
Drugs
Tenofovir (TDF)
Zidovudine (AZT)
Lamivudine (3TC)
Abacavir (ABC)
Adverse effects
Renal toxicity, bone demineralization
Anaemia, neutropenia, bone marrow suppression
gastrointestinal intolerance, headache, insomnia,
myopathy, lactic acidosis, hyperpigmentation of skin and nail
Minimal toxicity, rash (very rare)
Hypersensitivity reaction in 3% to 5% (can be fatal), fever,
rash, fatigue, nausea, vomiting, anorexia, respiratory
symptoms (sore throat, cough, shortness of breath);
rechallenging after reaction can be fatal
Adverse drug effects of ARVs......cont’d…
Drugs
Dolutegravir (DTG)
Raltegravir (RAL)
Atazanavir/ ritonavir (ATV/r)
Lopinavir/ritonavir (LPV/r)
Adverse effects
Hepatotoxicity, weight gain, allergic reaction, insomnia
Hepatotoxicity, allergic reaction, myalgia/rhabdomyolysis
Hyperbilirubinaemia, Hyperglycaemia,
fat maldistribution, nephrolithiasis
Diarrhoea, nausea, vomiting, abnormal lipid profiles,
glucose intolerance
Note: PI’s should not be prescribed with Simvastatin as they significantly increase the
level of Simvastatin leading to Rhabdomyolysis, resulting in severe kidney failure.
ADHERENCE
 Adherence signifies that the patient and physician collaborate to improve the
patient’s health by integrating the physician’s medical opinion and the patient’s lifestyle,
values and preferences to care.
 Patients starting ART should be willing and able to commit to treatment and understand
the benefits and risks of therapy and the importance of adherence.
 For ART, a high level of sustained adherence is necessary to
1. suppress viral replication and improve immunological and clinical outcomes;
2. decrease the risk of developing ARV drug resistance; and
3. reduce the risk of transmitting HIV
 Adherence should be assessed and routinely reinforced by everyone in the
HIV care team at each of the patient’s visit to the ART centre.
 Studies indicate that >95% of adherence is required for optimal viral load suppression.
 Lesser degree of adherence is often associated with virological failure
Prophylaxis
Co-trimoxazole prophylaxis :
CPT must be initiated in all HIV-infected adults and adolescent with CD4 count <350
cells/mm3 or those with WHO clinical stage 3 or 4, to prevent PCP and Toxoplasmosis.
One tablet of Cotrimoxazole -DS (Trimethoprim 160 mg + Sulphamethoxazole 800 mg) to
be taken daily preferably after food.
Note: For patient’s allergic to co-trimoxazole, Dapsone 100mg is given as prophylaxis.
TB Preventive Therapy:
Three months after initiation of ART, All patients who do not have active TB should be
considered for prophylaxis to prevent latent TB from progressing to active TB. It also
prevents re-infection after exposure to an open case of TB.
One tablet of Isoniazid 300 mg to be taken daily preferably after food for 6 months .
Note: IPT does not promote Isoniazid resistance when used to treat latent TB infection In
latent TB, the Mycobacterium tuberculosis bacilli are fewer in number and are dividing
slowly, resulting in an extremely low risk of selecting drug-resistant mutants.
Stable Adults and adolescents (>10 years)
PLHIV (Adult/Adolescent) shall be termed ‘stable’ if they fulfil all the following criteria:
1. On ART for at least 6 months
2. No adverse effects of ART that require regular monitoring
3. No current illness/OI/medical condition that requires management
4. Suppressed plasma viral load (< 1000 copies/ml)
5. Treatment adherence ≥ 95% consecutively over the last 3 months
Definitions of treatment failure
Failure Definition Comments
Virological failure Plasma viral load ≥1000 copies/ml An individual must be taking
ART for at least 6 months
before it can be determined
that a regimen has failed.
Immunological failure CD4 count at 250 cells/ mm3
following clinical failure
Persistent CD4 count below
100 cells/mm3
Concomitant or recent
infection may cause a
transient decline in the CD4
cell count.
Clinical failure New or recurrent clinical event
indicating severe immuno-
deficiency (WHO clinical stage 4)
after 6 months effective treatment.
The condition must be
differentiated from IRIS
Substitution, Step-up Adherence and Switch
SUBSTITUTION:
Substitution refers to replacement of ARV drug in a virally suppressed PLHIV
due to adverse effects of drug, drug–drug interactions or programme policy.
This does not indicate change of regimen due to treatment failure.
STEP-UP ADHERENCE:
In all patients with treatment failure (Plasma viral load ≥ 1000 copies/ml),
Step-up adherence counselling is done for three months and viral load test
repeated if adherence is > 95% in the three consecutive months.
SWITCH:
Treatment failure refers to the loss of antiviral efficacy to the current regimen.
When the ARV regimen is changed because of treatment failure, it is referred
as the switch of the entire regimen.
Change of Line of Regimen
First-line ART: is the initial regimen prescribed for an ART-naive patient.
Second-line ART: is the subsequent regimen used in sequence immediately after first-line
therapy has failed (as recommended by SACEP at ART Plus Centre).
Third-line ART: is the subsequent regimen used in sequence immediately after second-line
therapy has failed (as recommended by COE at Bengaluru and treatment at ART Plus centre).
Current Recommendation for Second-line ART is based on the following :
an integrase strand transfer inhibitor (INSTI)-DTG, if first line was NNRTI based „
a Ritonavir-boosted PI (Atazanavir/ritonavir or Lopinavir/ritonavir), if first line was INSTI based
Supported by at least one new and unused NRTI (Zidovudine or Tenofovir)
Continued Lamivudine administration ensures reduced viral fitness.
Initiation of third-line ART :
Third-line regimens should include new drugs with minimal risk of cross-resistance to
previously used regimens such as INSTIs and second-generation NNRTIs and PIs.
The regimen is Dolutegravir (50 mg) +[ Darunavir (600 mg) + ritonavir (100 mg) BD].
ARV for Pregnant Women and Exposed Infant
All Pregnant women should be screened for HIV and HIV-positive pregnant women
including those presenting in labour and breastfeeding should be initiated on a
triple-drug (TLD) regimen regardless of CD4 count and clinical stage for preventing
MTCT and should continue lifelong ART.
The incidence of neural tube defects with the use of DTG is < 0.2%
Women of childbearing potential or pregnant women (first trimester) who do not
wish to take DTG based ART after adequate and optimal counselling are given
Tenofovir (300 mg) + Lamivudine (300 mg) once daily
Lopinavir (200 mg) + ritonavir (50 mg) twice daily
Viral load test is done between 32 and 36 weeks of pregnancy to assess
high or Iow risk of transmission to the infant
ARV Prophylaxis is advised to the infant based on the risk of HIV transmission.
HIV risk assessment of infants and ARV Prophylaxis
Low-risk infants:
Infants born to mothers with suppressed
viral load(<1000 copies/ ml) done anytime after
32 weeks of pregnancy or up to delivery
High-risk infants:
* Infants born to HIV-positive mother not on ART
* Maternal viral load not done after 32 weeks of
pregnancy till delivery
* Maternal viral load not suppressed between
32 weeks of pregnancy till delivery
* Mother newly identified HIV positive within
6 weeks of delivery
HIV Risk Status Option for ARV Prophylaxis
Syrup Nevirapine (NVP) or Syrup Zidovudine
(where NVP will not be effective):
a)Infant born to a mother with confirmed HIV-2 or
HIV-1 and HIV-2 combined infections
b) Infant born to a mother who had received single
dose of NVP during earlier pregnancy or delivery
c) Infant born to a mother who is on PI-based ART
regimen due to treatment failure
Duration of ARV prophylaxis:
From birth till 6 weeks of age
Options for dual prophylaxis:
Syrup Nevirapine + Syrup Zidovudine
Duration of Dual ARV Prophylaxis:
a) In case of Exclusive Replacement Feeding (ERF):
From birth till 6 weeks of age
b) In case of Exclusive Breastfeeding (EBF):
From birth till 12 weeks of age
Infant feeding
The two infant feeding options available for the HIV-positive mother are
Exclusive breast feeding (EBF) or Exclusive replacement feeding (ERF)
EBF means giving a baby only breast milk and no other liquids or solids.
ERF is the process of feeding a baby, who is not breastfeeding, with a diet that provides
the baby its nutrient requirements which includes feeding the baby animal milk, dairy milk,
and infant formulas. It is important to counsel parents that the feed must be prepared
in a hygienic manner and should be give with a spoon and bowl. Avoid bottle feeding.
Mothers living with HIV should breastfeed for at least 12 months while being fully
supported for ART adherence
Breastfeeding is made safe by giving ART to the mother and ARV prophylaxis to the baby.
Mixed feeding increases the risk of transmission of HIV and should be avoided.
Children and HIV
• Age less than 6 years and body weight
less than 20 kg
• Age between 6 and 10 years and body
weight between 20 kg and 30 kg
• Age more than 10 years and body
weight more than 30 kg
First-line ART regimens for infants and children with HIV-1 and HIV-2 infection
Particulars Recommended Regimen
• Abacavir + Lamivudine +
Lopinavir/ritonavir (AL+LPV/r)
• Abacavir + Lamivudine +
Dolutegravir (ALD)
• Tenofovir + Lamivudine +
Dolutegravir (TLD)
Please note:
Any infant or child initiated on any regimen must be based on body weight.
On every visit, check body weight of the infant/child before writing the prescription.
Even though the drug regimen remains the same, drug dosages have to be modified
according to change in body weight.
Prophylaxis in children
Weight (kg) Age Syrup 5 ml (40 TMP/200
SMX)
Child tab. (20 TMP/100 SMX)
< 5 6 wks –2 months 2.5ml 1 tablet
5 - 10 2- 12 months 5ml 2 tablets
10 - 15 1- 2 years 7.5ml 3 tablets
15 – 22 2 - 5 years 10ml 4 tablets
>22 > 5 years 15ml 1 ½ (adult) tablets
Co-trimoxazole prophylaxis:
(Weight and Age based dosing)
IPT Prophylaxis:
Dosage of Isoniazid in children
Weight range (kg) Number of 100 mg tablets of INH
(total dose 10 mg/kg/day)
< 5 ½ tablet
5.1– 9.9 1 tablet
10– 13.9 1 ½ tablets
14– 19.9 2 tablets
20– 24.9 2 ½ tablets
> 25 3 tablets or one adult tablet (300mg)
Stable Child
For children >2 years to 10 years of age, satisfying all the following criteria:
Receiving ART for at least 6 months
Viral load is suppressed (Plasma viral load < 1000 copies/ml)
Should be on the same regimen ( with no dose or formulation change)
for at least 3 months
Should not have any active illness or medical condition that
requires further management
Treatment adherence > 95% in each of last 3 months
Weight for age is more than 2SD
HIV-TB coinfection
The general principles for management of HIV-TB coinfected patients:
• Intensified Case Finding (ICF) using 4S Complex, fast tracking and
referral of symptomatic patients for CBNAAT.
• Prompt treatment of active TB and continuation of ART in PLHIV.
• Cotrimoxazole Preventive Therapy (CPT) in all PLHIV with TB co-infection.
Intensive phase: (IP) for 8 weeks:
Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E)
given in daily dosages as per adult and children weight band categories.
Continuation phase: (CP) for 16 weeks:
Isoniazid, Rifampicin and Ethambutol in daily dosages.
Note: 1. The CP may be extended by 12–24 weeks in certain forms of TB like CNS TB,
skeletal TB, disseminated TB, etc.
2. Dolutegravir 50 mg (at an interval of 12 hrs with the regular dose of DTG)
is given and continued for 2 weeks after completion of ATT.
HIV-TB coinfection……cont’d…
Adverse drug effects of first-line anti-TB drugs
Drug
• Isoniazid
• Rifampicin
• Pyrazinamide
• Ethambutol
Main Effects
• Peripheral neuropathy
• Skin rash
• Hepatitis
• Sleepiness and lethargy
• Abdominal pain, nausea, vomiting
• Hepatitis
• General cutaneous reactions
• Thrombocytopenic purpura
• Arthralgia
• Hepatitis
• Gastrointestinal problems
• Retrobulbar neuritis
Post-exposure Propyhlaxis (PEP)
Management of Exposure Site – First Aid
Skin:
If the skin is pierced by a needlestick or sharp instrument:
• Immediately wash the wound and surrounding skin with water and soap.
• Do not scrub.
• Do not use antiseptics or skin washes.
• Do not use bleach, chlorine, alcohol, betadine.
After a splash of blood or body fluids:
• Wash the area immediately.
• Do not use antiseptics.
Unbroken skin:
• Wash the area immediately.
• Do not use antiseptics.
Eye:
• Irrigate exposed eye immediately with water or normal saline.
• If wearing contact lenses, leave them in place while irrigating, as they form a barrier.
Mouth:
• Spit fluid out immediately.
• Rinse the mouth thoroughly using water or saline and spit again. Repeat this process.
Mild exposure
Types of exposure
Exposure to mucous membrane/non-intact skin with
small volumes, contact with the eyes or mucous
membranes or subcutaneous injections following
small-bore needle
Exposure to mucous membrane with large
volumes or percutaneous superficial exposure
with solid needle. e.g., a superficial cut or
needlestick injury penetrating gloves
Percutaneous exposure with large volume e.g.
• an accident with a high-calibre needle (>18 G)
visibly contaminated with blood
• a deep wound (haemorrhagic wound and/or very
painful); transmission of a significant volume of blood
• an accident with material that has previously been
used intravenously or intra-arterially
Post-exposure Prophylaxis……cont’d…
Moderate exposure
Severe exposure
HIV Exposure Codes (EC)
Whether the material is blood, bloody fluid or other potentially infected material
(OPIM) or instrument contaminated with one of these substances
Yes No PEP not required
What type of exposure occurred?
Mucous membrane or
skin integrity
compromised
Intact skin
Percutaneous exposure
Volume
Small volume/ a
few drops short
duration
EC 1
Large volume/
major splash long
duration
EC 2
Severity
Less severe, solid
needle, superficial
scratch
More severe, hollow-
bore needle deep
injury
EC 2 EC 3
PEP not required
Post-exposure Prophylaxis……cont’d…
HIV Source Codes (SC)
Source of exposure: HIV status
HIV-negative HIV-positive HIV status unknown
PEP not required Low titre exposure
asymptomatic high
CD4 count
High titre exposure
advanced disease
low CD4 count
HIV SC: Unknown
HIV SC 1 HIV SC 2
Post-exposure Prophylaxis……cont’d…
Post-exposure Prophylaxis……cont’d…
NACO recommendations for PEP
Exposure Code HIV Source Code Recommendation for PEP
1 1 Not warranted
1 2 Recommended PEP
2 1 ………………...
2 2 ………………...
3 1 or 2 …………………
2 or 3 Unknown Consider PEP if HIV
prevalence is high in
population in the region
and risk categorization
Post-exposure Prophylaxis……cont’d…
Exposure to Body Fluids Considered `at Risk'
• Blood
• Semen
• Vaginal secretions
• Cerebrospinal fluid
• Synovial, pleural, peritoneal,
pericardial fluid, Amniotic fluid
• Other body fluids contaminated
with visible blood
Exposure to Body Fluids Considered ‘Not at Risk‘
( Unless these Fluids Contain Visible Blood )
• Tears
• Sweat
• Urine and faeces
• Saliva
• Sputum
• Vomitus
Post-exposure Prophylaxis……cont’d…
• Blood transfusion
• Perinatal (without any intervention)
• Sexual intercourse
• Vaginal
• Anal
• Oral
• Injecting drugs use
• Needle Stick exposure
• Mucous membrane splash to eye, oro-nasal
HIV transmission risk by different routes (WHO data)
Exposure Route HIV Transmission Rate
> 98%
20 - 40%
0.1–10%
0.05-0.1
0.065–0.5%
0.005–0.01%
0.67%
0.3%
0.09%
Note:
Comparative risk after needle-stick injury for HBV is 9% to 30% and for HCV is 1% to 1.8%
Post-exposure Prophylaxis……cont’d…
Exposed Person Regimen for PEP Alternate Regimen
Adolescents and Adults
(>10 yrs and >30 kg)
TLD TL + Lopinavir/Ritonavir
Children
(>6 yrs and <10 yrs and >20 kg) ZLD
Children (<6 yrs and <20 kg) Zidovudine + Lamivudine
+ Lopinavir/ritonavir
if Hb < 9 gm/dl
Abacavir+ Lamivudine
+ Dolutegravir
if Hb < 9 gm/dl
Abacavir+ Lamivudine
+ Lopinavir/ ritonavir
Duration of PEP is 28 days, regardless of PEP regimen
Check for HIV-Ab after 6 weeks, 3 months and 6 months
PEP must be initiated ideally within 2 hrs and preferably within 72 hours
JSS ART
Statistical data as on 1-12-2022
Pre-ART Registered 1911
Started on ART 1749
Alive on ART 1162
ANC’S on ART 02
CLHIV 10
HIV-TB co-infection 09
From 1st December2012
Key Points...
• Adherence to ART is the key.
• ART is not an emergency.
• First treat ongoing opportunistic infections.
• TLD is the most commonly used regimen.
• Prevention of MTCT is of utmost importance.
• PEP should be taken as early as possible.

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ART PPT Final.pptx

  • 1. Anti Retroviral Therapy Dr . B.K. Shiva Kumar, MD Medical Officer, ART Centre JSS Hospital, Mysuru
  • 2. FOCUS  DIAGNOSIS OF HIV  CLINICAL ASSESSMENT  DRUGS, REGIMEN AND MONITORING  PREGNANCY, INFANTS AND CHILDREN WITH HIV  HIV-TB CO-INFECTION  POST EXPOSURE PROPHYLAXIS
  • 3. HUMAN IMMUNODEFICIENCY VIRUS First ever known case of HIV infection was diagnosed in June 1981 in Los Angeles, USA. In India, first detected among female sex workers screened for HIV at Chennai in 1986. In Karnataka, at Saudatti in Belgavi district (Devadasi Rituals) in 1987. HIV infection is now considered a chronic manageable disease and majority of the PLHIV remain healthy if correct and timely treatment is started. Prevalence: As per India HIV estimation report 2020, HIV prevalence was estimated at 0.22% (0.24% among males; 0.20% among females). The prevalence continued to decline 0.54% in 2001 0.33% in 2010 0.22% in 2020 0.21% in 2021 ………………..24.01 Lakhs (Third Highest in World)
  • 4. Modes of Transmission At Risk Population ! a) Sex workers b) Truckers c) Migrants d) Trans-genders e) IV drug abusers 1. Sexual: a) Heterosexual b) MSM 2. Blood transfusion 3. Mother to child 4. Injection drug abuse 5. Needle stick injury, blood and body fluids splash.
  • 5. NATIONAL AIDS CONTROL ORGANIZATION(NACO) Policies for prevention and control of HIV infection  NACP-I started in 1992 and lasted until 1999.  NACP-II (2000–2005)  NACP-III (2006-2011)  NACP-IV (2012–2017)------( extended till March 2021).  NACP-V (2021-2026) 95% of the estimated PLHIV know their status, of which 95% PLHIV are on ART, of which 95% PLHIV have viral suppression
  • 6. In the current phase of NACP-V (2021–2026), the focus is on ensuring PLHIV survive longer and lead productive lives. This will be achieved through improving retention in HIV care and adherence to ART through a client-centric approach to providing care, support and treatment services. The current strategic plan aims to achieve: • zero new infections • zero AIDS-related deaths • zero discrimination for paving the way for an end of AIDS as a public health threat by 2030.
  • 7. NACO • NATIONAL SACS (KSAPS) • STATE ART CENTRE • DISTRICT LINK ART • TALUK
  • 8. SOCH: Strengthening Overall Care for HIV beneficiaries
  • 9. Consent Confidentiality Counselling • Pre test counselling • Post test counselling Integrated Counselling and Testing Centre (ICTC) Diagnosis of HIV
  • 10. In adults and children > 18 months: In infants and children < 18 months: Rapid tests (Sensitivity of >99.5 % and Specificity of >98 %) Total Nucleic Acid PCR test on a Dried Blood Spot
  • 11. Window period Window period: the period between infection with HIV and the time when HIV antibodies can be detected in the blood (6–12 weeks). A blood test performed during the window period may yield a negative test result for HIV antibodies.
  • 12. Maternal antibodies to HIV, transferred passively to the infant during pregnancy Usually persist for nearly 9–12 months in the infant. In some children, they may persist for as long as 18 months. Maternal antibodies
  • 13. Features of HIV-2 Less pathogenic and slower progression of disease Longer asymptomatic stage and lower viral loads Slower decline in CD4 counts Lower rates of vertical transmission • Patients with dual infection (HIV-1 and HIV-2) tend to present at a more advanced stage of the disease. • Infection with both HIV-1 and HIV-2 generally carries the same prognosis as that of HIV-1 single infection. Types of HIV Virus
  • 14. Goals of ART Clinical goal •Increased survival and improvement in quality of life Virological goal •Greatest possible sustained reduction in viral load Immunological goal •Immune reconstitution i.e, quantitative increase in CD4 Therapeutic goal •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 Preventive goal •Reduction of HIV transmission by suppression of viral load
  • 15. Scope of services Pregnancy and HIV Patients with HIV HIV TB co-infection Infants and Children with HIV Infants and Children with HIV Post Exposure Prophylaxis
  • 16. Patient Registration Rapid initiation of ART within 7 days from diagnosis ART Number allotted, once the ART is started Green book (details of the treatment will be entered, to be brought during each visit) White Card (demographic details, clinical parameters, lab values and details of treatment) Each patient will be given a Pre- ART number Address proof, Aadhaar card and 2 photos Patients should have ICTC report
  • 17. Clinical Assessment Once the PLHIV are enrolled in an ART centre, a comprehensive clinical assessment should be done to obtain baseline clinical status and to rule out OIs.
  • 18. Medical History  4 symptom screening for TB : Adults: fever, cough, weight loss, night sweats; Children: fever, cough, poor weight gain, h/o contact with a TB case  Persistent symptoms – headache, poor concentration, seizures;  Medical history for comorbid conditions like Diabetes and Hypertension;  History of tuberculosis;  Prior exposure to ARVs in the past;  History of STI;  HIV risk behaviour – multiple partners, key populations, injecting drug use;  Substance abuse – alcohol, tobacco, oral or injecting drugs;  Allergies/medication/vaccines;  Pregnancy and contraception.
  • 19. Physical Examination Appearance: pallor, icterus, orientation, wasting Vital signs: height, weight, temperature, blood pressure Skin: herpes simplex, herpes zoster, PPE Lymph nodes: cervical, axillary and inguinal Mouth: oral candidiasis, oral hairy leukoplakia Chest: congestion, consolidation Abdomen: hepato-spenomegaly, tenderness Neurological: comprehensive Eyes: fundus examination if CD4 < 100 cells/cu mm. Anogenital : genital lesions, urethral or vaginal discharge
  • 20. Laboratory monitoring Baseline Investigations  Haemogram/CBC  Fasting blood sugar  Blood urea, serum creatinine  LFT  Lipid profile  VDRL  HBsAg  HCV  Serum cryptococcal antigen  CD4 count  Urine for routine and microscopy  X-ray Chest  USG Abdomen  CBNAAT
  • 21. WHO Clinical Staging - Stage I • Asymptomatic • Persistent generalized lymphadenopathy • Asymptomatic • Persistent generalized lymphadenopathy  Adults and adolescents  Children
  • 22. WHO Clinical Staging -Stage II  Children • Unexplained hepato-splenomegaly • Recurrent respiratory tract infections (Otitis Media, Sinusitis, Tonsillitis) • Herpes zoster • Lineal gingival erythema • Recurrent oral ulceration • Papular pruritic eruption • Fungal nail infections • Extensive wart virus infection • Extensive Molluscum contagiosum • Persistent parotid enlargement  Adults and adolescents • 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
  • 23. • Unexplained severe weight loss (>10% of the presumed or measured body weight) • Chronic diarrhoea for more than 1 month • 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) • Acute necrotizing ulcerative stomatitis, gingivitis or Periodontitis • Unexplained anaemia (Hb < 8 g/dl ) • Unexplained moderate malnutrition not responding to standard therapy • Chronic diarrhoea (14 days or more) • Persistent fever (intermittent or constant, for longer than 1 month) • Persistent Oral Candidiasis (after the first 6 weeks of life) • Oral Hairy Leukoplakia • Lymph node Tuberculosis • Pulmonary Tuberculosis • Severe recurrent bacterial Pneumonia • Acute necrotizing ulcerative stomatitis, gingivitis or Periodontitis • Unexplained anaemia (Hb < 8 gm/dl)  Adults and adolescents  Children WHO Clinical Staging - Stage III
  • 24.  Children • Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy • Pneumocystis (jiroveci) 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 duration or visceral at any site) • Oesophageal Candidiasis (or Candidiasis of • trachea, bronchi, or lungs) • Extra pulmonary Tuberculosis • Kaposi’s sarcoma • Cytomegalovirus infection (retinitis or infection of other organs with onset at age > 1 month)  Adults and adolescents • HIV wasting syndrome • Pneumocystis (jiroveci) Pneumonia • Recurrent severe bacterial Pneumonia • Chronic Herpes Simplex infection (orolabial, genital or anorectal of more than 1 month duration or visceral at any site) • Oesophageal Candidiasis (or Candidiasis of trachea, bronchi or lungs) • Extra pulmonary Tuberculosis • Kaposi’s sarcoma • Cytomegalovirus infection (retinitis or infection of other organs) • Central nervous system Toxoplasmosis • HIV encephalopathy • Extra pulmonary Cryptococcosis, including Meningitis WHO Clinical Staging - Stage IV
  • 25.  Children • Central nervous system Toxoplasmosis (after the neonatal period) • HIV encephalopathy • Extra pulmonary Cryptococcosis, including Meningitis • Disseminated nontuberculous mycobacterial infection (NTM) • Progressive Multifocal Leukoencephalopathy • Chronic Cryptosporidiosis (with diarrhoea) • Chronic Isosporiasis • Disseminated mycosis (extra pulmonary Histoplasmosis, Coccidioidomycosis, Penicilliosis) • Cerebral or B-cell non-Hodgkin’s Lymphoma • HIV-associated nephropathy or cardiomyopathy  Adults and adolescents • Disseminated non-tuberculous mycobacterial infection (NTM) • Progressive Multifocal Leukoencephalopathy (PML) • Chronic Cryptosporidiosis • Chronic Isosporiasis • Disseminated mycosis (extra pulmonary Histoplasmosis, Coccidioidomycosis) • Lymphoma (cerebral or B-cell nonHodgkin’s) • HIV-associated nephropathy or cardiomyopathy • Recurrent septicaemia (including nontyphoidal Salmonella) • Invasive cervical carcinoma • Atypical disseminated leishmaniasis WHO Clinical Staging - Stage IV ......cont’d...
  • 26. Association between CD4 and opportunistic infections
  • 27. Management of OI’s before ART initiation Clinical Picture Action Tuberculosis ART should be started as soon as possible within 2 weeks of initiating TB treatment, regardless of CD4 cell count Pneumocystis pneumonia (PCP) Treat PCP first; start ART when PCP treatment is completed Oesophageal candidiasis Cryptococcal meningitis Treat oesophageal candidiasis first; start ART as soon as the patient can swallow Cytomegalovirus Retinitis Treat CMV urgently; start ART after 2 weeks Toxoplasmosis Treat Toxoplasmosis; start ART after 6 weeks Treat cryptococcal meningitis, start ART after 4-6 weeks when the patient is stabilized
  • 28. HIV life cycle andARV targets
  • 29. ART DRUGS ENTRY INHIBITORS : • HIV enters CD4 cells via CD4 receptor in conjugation with one of its co-receptors – CCR5 & CXCR4. • CCR5 Antagonist – MARAVIROC– used only in treatment experienced patients with drug resistant virus. • FUSION inhibitors – ENFUVIRTIDE – bind to GP41 (envelope protein of HIV) and prevent their fusion with T-cell. • ATTACHMENT inhibitor – FOSTEMSAVIR – approved in 2020 that bind to GP120 (envelope protein of HIV) and prevent HIV fusion with CD4 T cell.
  • 30. REVERSE TRANSCRIPTASE INHIBITORS: A. Nucleotide Reverse Transcriptase Inhibitors (NtRTI) • TENOFOVIR* – Alafenamide (TAF) & Disoproxil fumarate (TDF)* B. Nucleoside Reverse Transcriptase Inhibitors (NRTI) • ABACAVIR (ABC) * • LAMIVUDINE (3TC) * • ZIDOVUDINE (AZT)* • EMTRICITABINE (FTC) • DIDANOSINE (ddi) • STAVUDINE (d4T) C. Non- Nucleoside Reverse Transcriptase Inhibitors (NNRTI) • NEVIRAPINE (NVP) * • EFAVIRENZ (EFV) * • DELAVIRIDINE • RILPIVIRINE • ETRAVIRINE
  • 31. INTEGRASE INHIBITORS: • DOLUTEGRAVIR (DTG) * • RALTEGRAVIR (RGV) * • ELVITEGRAVIR • BICTEGRAVIR • CABOTEGRAVIR PROTEASE INHIBITORS: • RITONAVIR (RTV) * • LOPINAVIR (LPV) * • ATAZANAVIR (ATV) * • DARUNAVIR (DRV) * • SAQUINAVIR • NELFINAVIR • INDINAVIR • AMPRENAVIR
  • 32. Optimal Regimen Based on the evidence supporting better efficacy and fewer side effects, the preferred first-line ART regimen for PLHIV is as follows: Age > 10 yrs and weight > 30 kg Tenofovir(300mg) + Lamivudine (300 mg) + Dolutegravir(DTG 50 mg) TLD regimen as FDC in a single pill once daily PLHIV with body weight < 30 kg ABC (600 mg) + Lamivudine (300mg)+ DTG (50 mg) ABC (600 mg OD) + Lamivudine (as per creatinine clearance**) and DTG (50 mg) All patients with high serum Creatinine Values(above ULN) PLHIV on Rifampicin-containing ATT regimen TLD + additional dose of DTG 50 mg (12 hours after taking their regular dose) until 2 weeks after completion of ATT
  • 33. Monitoring and follow up Patients are advised to visit ART regularly every month Body weight (Height in children) Treatment Adherence 4-Symptom TB screening Screening for HTN, Diabetes Every visit Every visit Every visit Every visit Lab Investigations: Hb, RBS, SGOT, SGPT, Urea, Creatinine Every 6 Months CD4 count: • CD4 must be done every 6 months, can be discontinued if it reaches > 350 cells/mm3 and viral load is < 1000 copies/ml (when both tests are conducted at the same time). Viral load: • Viral load at 6 months, 12 months and then every 12 months • For patients on second/third-line ART, Viral Load testing to be done every 6 months Advanced HIV Disease: PLHIV with advanced HIV disease are defined as presenting with CD4 count < 200 cells/cu.mm. or WHO clinical stage 3 or 4 or children aged < 5 years
  • 34. Expected response to ART • Virological response to ART: The plasma viral load done 6 months after initiation of ART should come down to<1000 copies/ml and should be maintained at undetectable or <1000 copies/ ml throughout the treatment course • Immunological response to ART: is defined as an increase of at least 50 CD4 cells/mm3 at 6 months of ART. This increase is usually 50–100 cells/mm3 within 6–12 months of ART initiation in ARV-naive patients, who are fully adherent to ART • Clinical response to ART: Clinical monitoring should include evaluation of weight, general well-being (functional status), adverse reaction to drugs and keeping an eye out for IRIS, especially in patients with low CD4 count
  • 35. IRIS Immune Reconstitution Inflammatory Syndrome The worsening of signs and symptoms due to known infections, or the development of disease due to occult infections within 6 weeks to 6 months after initiating ART, with an increase in CD4 count. IRIS should be diagnosed by excluding the following; a) Active OI, b) Treatment failure, c) Side effect from ARV, d) Failure to antimicrobial therapy The most serious and life-threatening forms of paradoxical IRIS are TB and Cryptococcosis. Important steps to reduce the development of IRIS include; • Earlier HIV diagnosis and initiation of ART before decline of CD4 below 200 cells/mm3 • Improved screening for OIs before ART, especially TB, Cryptococcus, CMV and optimal management of OIs before initiating ART. IRIS is generally self-limiting and interruption of ART is rarely indicated Anti microbial therapy is required to reduce and eliminate triggering pathogen Short-term therapy with corticosteroids or non-steroidal anti-inflammatory drugs Temporary cessation of ART must be considered, only in potentially life-threatening forms of IRIS Risk factors for IRIS: 1) People with CD4 counts below 100 cells/cu mm at ART initiation 2) People with rapid initial fall in HIV viral load due to therapy 3) Shorter interval between OI therapy initiation and ART initiation 4) Higher HIV RNA at ART initiation
  • 36. Adverse drug effects of ARVs Drugs Tenofovir (TDF) Zidovudine (AZT) Lamivudine (3TC) Abacavir (ABC) Adverse effects Renal toxicity, bone demineralization Anaemia, neutropenia, bone marrow suppression gastrointestinal intolerance, headache, insomnia, myopathy, lactic acidosis, hyperpigmentation of skin and nail Minimal toxicity, rash (very rare) Hypersensitivity reaction in 3% to 5% (can be fatal), fever, rash, fatigue, nausea, vomiting, anorexia, respiratory symptoms (sore throat, cough, shortness of breath); rechallenging after reaction can be fatal
  • 37. Adverse drug effects of ARVs......cont’d… Drugs Dolutegravir (DTG) Raltegravir (RAL) Atazanavir/ ritonavir (ATV/r) Lopinavir/ritonavir (LPV/r) Adverse effects Hepatotoxicity, weight gain, allergic reaction, insomnia Hepatotoxicity, allergic reaction, myalgia/rhabdomyolysis Hyperbilirubinaemia, Hyperglycaemia, fat maldistribution, nephrolithiasis Diarrhoea, nausea, vomiting, abnormal lipid profiles, glucose intolerance Note: PI’s should not be prescribed with Simvastatin as they significantly increase the level of Simvastatin leading to Rhabdomyolysis, resulting in severe kidney failure.
  • 38. ADHERENCE  Adherence signifies that the patient and physician collaborate to improve the patient’s health by integrating the physician’s medical opinion and the patient’s lifestyle, values and preferences to care.  Patients starting ART should be willing and able to commit to treatment and understand the benefits and risks of therapy and the importance of adherence.  For ART, a high level of sustained adherence is necessary to 1. suppress viral replication and improve immunological and clinical outcomes; 2. decrease the risk of developing ARV drug resistance; and 3. reduce the risk of transmitting HIV  Adherence should be assessed and routinely reinforced by everyone in the HIV care team at each of the patient’s visit to the ART centre.  Studies indicate that >95% of adherence is required for optimal viral load suppression.  Lesser degree of adherence is often associated with virological failure
  • 39. Prophylaxis Co-trimoxazole prophylaxis : CPT must be initiated in all HIV-infected adults and adolescent with CD4 count <350 cells/mm3 or those with WHO clinical stage 3 or 4, to prevent PCP and Toxoplasmosis. One tablet of Cotrimoxazole -DS (Trimethoprim 160 mg + Sulphamethoxazole 800 mg) to be taken daily preferably after food. Note: For patient’s allergic to co-trimoxazole, Dapsone 100mg is given as prophylaxis. TB Preventive Therapy: Three months after initiation of ART, All patients who do not have active TB should be considered for prophylaxis to prevent latent TB from progressing to active TB. It also prevents re-infection after exposure to an open case of TB. One tablet of Isoniazid 300 mg to be taken daily preferably after food for 6 months . Note: IPT does not promote Isoniazid resistance when used to treat latent TB infection In latent TB, the Mycobacterium tuberculosis bacilli are fewer in number and are dividing slowly, resulting in an extremely low risk of selecting drug-resistant mutants.
  • 40. Stable Adults and adolescents (>10 years) PLHIV (Adult/Adolescent) shall be termed ‘stable’ if they fulfil all the following criteria: 1. On ART for at least 6 months 2. No adverse effects of ART that require regular monitoring 3. No current illness/OI/medical condition that requires management 4. Suppressed plasma viral load (< 1000 copies/ml) 5. Treatment adherence ≥ 95% consecutively over the last 3 months
  • 41. Definitions of treatment failure Failure Definition Comments Virological failure Plasma viral load ≥1000 copies/ml An individual must be taking ART for at least 6 months before it can be determined that a regimen has failed. Immunological failure CD4 count at 250 cells/ mm3 following clinical failure Persistent CD4 count below 100 cells/mm3 Concomitant or recent infection may cause a transient decline in the CD4 cell count. Clinical failure New or recurrent clinical event indicating severe immuno- deficiency (WHO clinical stage 4) after 6 months effective treatment. The condition must be differentiated from IRIS
  • 42. Substitution, Step-up Adherence and Switch SUBSTITUTION: Substitution refers to replacement of ARV drug in a virally suppressed PLHIV due to adverse effects of drug, drug–drug interactions or programme policy. This does not indicate change of regimen due to treatment failure. STEP-UP ADHERENCE: In all patients with treatment failure (Plasma viral load ≥ 1000 copies/ml), Step-up adherence counselling is done for three months and viral load test repeated if adherence is > 95% in the three consecutive months. SWITCH: Treatment failure refers to the loss of antiviral efficacy to the current regimen. When the ARV regimen is changed because of treatment failure, it is referred as the switch of the entire regimen.
  • 43. Change of Line of Regimen First-line ART: is the initial regimen prescribed for an ART-naive patient. Second-line ART: is the subsequent regimen used in sequence immediately after first-line therapy has failed (as recommended by SACEP at ART Plus Centre). Third-line ART: is the subsequent regimen used in sequence immediately after second-line therapy has failed (as recommended by COE at Bengaluru and treatment at ART Plus centre). Current Recommendation for Second-line ART is based on the following : an integrase strand transfer inhibitor (INSTI)-DTG, if first line was NNRTI based „ a Ritonavir-boosted PI (Atazanavir/ritonavir or Lopinavir/ritonavir), if first line was INSTI based Supported by at least one new and unused NRTI (Zidovudine or Tenofovir) Continued Lamivudine administration ensures reduced viral fitness. Initiation of third-line ART : Third-line regimens should include new drugs with minimal risk of cross-resistance to previously used regimens such as INSTIs and second-generation NNRTIs and PIs. The regimen is Dolutegravir (50 mg) +[ Darunavir (600 mg) + ritonavir (100 mg) BD].
  • 44. ARV for Pregnant Women and Exposed Infant All Pregnant women should be screened for HIV and HIV-positive pregnant women including those presenting in labour and breastfeeding should be initiated on a triple-drug (TLD) regimen regardless of CD4 count and clinical stage for preventing MTCT and should continue lifelong ART. The incidence of neural tube defects with the use of DTG is < 0.2% Women of childbearing potential or pregnant women (first trimester) who do not wish to take DTG based ART after adequate and optimal counselling are given Tenofovir (300 mg) + Lamivudine (300 mg) once daily Lopinavir (200 mg) + ritonavir (50 mg) twice daily Viral load test is done between 32 and 36 weeks of pregnancy to assess high or Iow risk of transmission to the infant ARV Prophylaxis is advised to the infant based on the risk of HIV transmission.
  • 45. HIV risk assessment of infants and ARV Prophylaxis Low-risk infants: Infants born to mothers with suppressed viral load(<1000 copies/ ml) done anytime after 32 weeks of pregnancy or up to delivery High-risk infants: * Infants born to HIV-positive mother not on ART * Maternal viral load not done after 32 weeks of pregnancy till delivery * Maternal viral load not suppressed between 32 weeks of pregnancy till delivery * Mother newly identified HIV positive within 6 weeks of delivery HIV Risk Status Option for ARV Prophylaxis Syrup Nevirapine (NVP) or Syrup Zidovudine (where NVP will not be effective): a)Infant born to a mother with confirmed HIV-2 or HIV-1 and HIV-2 combined infections b) Infant born to a mother who had received single dose of NVP during earlier pregnancy or delivery c) Infant born to a mother who is on PI-based ART regimen due to treatment failure Duration of ARV prophylaxis: From birth till 6 weeks of age Options for dual prophylaxis: Syrup Nevirapine + Syrup Zidovudine Duration of Dual ARV Prophylaxis: a) In case of Exclusive Replacement Feeding (ERF): From birth till 6 weeks of age b) In case of Exclusive Breastfeeding (EBF): From birth till 12 weeks of age
  • 46. Infant feeding The two infant feeding options available for the HIV-positive mother are Exclusive breast feeding (EBF) or Exclusive replacement feeding (ERF) EBF means giving a baby only breast milk and no other liquids or solids. ERF is the process of feeding a baby, who is not breastfeeding, with a diet that provides the baby its nutrient requirements which includes feeding the baby animal milk, dairy milk, and infant formulas. It is important to counsel parents that the feed must be prepared in a hygienic manner and should be give with a spoon and bowl. Avoid bottle feeding. Mothers living with HIV should breastfeed for at least 12 months while being fully supported for ART adherence Breastfeeding is made safe by giving ART to the mother and ARV prophylaxis to the baby. Mixed feeding increases the risk of transmission of HIV and should be avoided.
  • 47. Children and HIV • Age less than 6 years and body weight less than 20 kg • Age between 6 and 10 years and body weight between 20 kg and 30 kg • Age more than 10 years and body weight more than 30 kg First-line ART regimens for infants and children with HIV-1 and HIV-2 infection Particulars Recommended Regimen • Abacavir + Lamivudine + Lopinavir/ritonavir (AL+LPV/r) • Abacavir + Lamivudine + Dolutegravir (ALD) • Tenofovir + Lamivudine + Dolutegravir (TLD) Please note: Any infant or child initiated on any regimen must be based on body weight. On every visit, check body weight of the infant/child before writing the prescription. Even though the drug regimen remains the same, drug dosages have to be modified according to change in body weight.
  • 48. Prophylaxis in children Weight (kg) Age Syrup 5 ml (40 TMP/200 SMX) Child tab. (20 TMP/100 SMX) < 5 6 wks –2 months 2.5ml 1 tablet 5 - 10 2- 12 months 5ml 2 tablets 10 - 15 1- 2 years 7.5ml 3 tablets 15 – 22 2 - 5 years 10ml 4 tablets >22 > 5 years 15ml 1 ½ (adult) tablets Co-trimoxazole prophylaxis: (Weight and Age based dosing)
  • 49. IPT Prophylaxis: Dosage of Isoniazid in children Weight range (kg) Number of 100 mg tablets of INH (total dose 10 mg/kg/day) < 5 ½ tablet 5.1– 9.9 1 tablet 10– 13.9 1 ½ tablets 14– 19.9 2 tablets 20– 24.9 2 ½ tablets > 25 3 tablets or one adult tablet (300mg)
  • 50. Stable Child For children >2 years to 10 years of age, satisfying all the following criteria: Receiving ART for at least 6 months Viral load is suppressed (Plasma viral load < 1000 copies/ml) Should be on the same regimen ( with no dose or formulation change) for at least 3 months Should not have any active illness or medical condition that requires further management Treatment adherence > 95% in each of last 3 months Weight for age is more than 2SD
  • 51. HIV-TB coinfection The general principles for management of HIV-TB coinfected patients: • Intensified Case Finding (ICF) using 4S Complex, fast tracking and referral of symptomatic patients for CBNAAT. • Prompt treatment of active TB and continuation of ART in PLHIV. • Cotrimoxazole Preventive Therapy (CPT) in all PLHIV with TB co-infection. Intensive phase: (IP) for 8 weeks: Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E) given in daily dosages as per adult and children weight band categories. Continuation phase: (CP) for 16 weeks: Isoniazid, Rifampicin and Ethambutol in daily dosages. Note: 1. The CP may be extended by 12–24 weeks in certain forms of TB like CNS TB, skeletal TB, disseminated TB, etc. 2. Dolutegravir 50 mg (at an interval of 12 hrs with the regular dose of DTG) is given and continued for 2 weeks after completion of ATT.
  • 52. HIV-TB coinfection……cont’d… Adverse drug effects of first-line anti-TB drugs Drug • Isoniazid • Rifampicin • Pyrazinamide • Ethambutol Main Effects • Peripheral neuropathy • Skin rash • Hepatitis • Sleepiness and lethargy • Abdominal pain, nausea, vomiting • Hepatitis • General cutaneous reactions • Thrombocytopenic purpura • Arthralgia • Hepatitis • Gastrointestinal problems • Retrobulbar neuritis
  • 53. Post-exposure Propyhlaxis (PEP) Management of Exposure Site – First Aid Skin: If the skin is pierced by a needlestick or sharp instrument: • Immediately wash the wound and surrounding skin with water and soap. • Do not scrub. • Do not use antiseptics or skin washes. • Do not use bleach, chlorine, alcohol, betadine. After a splash of blood or body fluids: • Wash the area immediately. • Do not use antiseptics. Unbroken skin: • Wash the area immediately. • Do not use antiseptics. Eye: • Irrigate exposed eye immediately with water or normal saline. • If wearing contact lenses, leave them in place while irrigating, as they form a barrier. Mouth: • Spit fluid out immediately. • Rinse the mouth thoroughly using water or saline and spit again. Repeat this process.
  • 54. Mild exposure Types of exposure Exposure to mucous membrane/non-intact skin with small volumes, contact with the eyes or mucous membranes or subcutaneous injections following small-bore needle Exposure to mucous membrane with large volumes or percutaneous superficial exposure with solid needle. e.g., a superficial cut or needlestick injury penetrating gloves Percutaneous exposure with large volume e.g. • an accident with a high-calibre needle (>18 G) visibly contaminated with blood • a deep wound (haemorrhagic wound and/or very painful); transmission of a significant volume of blood • an accident with material that has previously been used intravenously or intra-arterially Post-exposure Prophylaxis……cont’d… Moderate exposure Severe exposure
  • 55. HIV Exposure Codes (EC) Whether the material is blood, bloody fluid or other potentially infected material (OPIM) or instrument contaminated with one of these substances Yes No PEP not required What type of exposure occurred? Mucous membrane or skin integrity compromised Intact skin Percutaneous exposure Volume Small volume/ a few drops short duration EC 1 Large volume/ major splash long duration EC 2 Severity Less severe, solid needle, superficial scratch More severe, hollow- bore needle deep injury EC 2 EC 3 PEP not required Post-exposure Prophylaxis……cont’d…
  • 56. HIV Source Codes (SC) Source of exposure: HIV status HIV-negative HIV-positive HIV status unknown PEP not required Low titre exposure asymptomatic high CD4 count High titre exposure advanced disease low CD4 count HIV SC: Unknown HIV SC 1 HIV SC 2 Post-exposure Prophylaxis……cont’d…
  • 57. Post-exposure Prophylaxis……cont’d… NACO recommendations for PEP Exposure Code HIV Source Code Recommendation for PEP 1 1 Not warranted 1 2 Recommended PEP 2 1 ………………... 2 2 ………………... 3 1 or 2 ………………… 2 or 3 Unknown Consider PEP if HIV prevalence is high in population in the region and risk categorization
  • 58. Post-exposure Prophylaxis……cont’d… Exposure to Body Fluids Considered `at Risk' • Blood • Semen • Vaginal secretions • Cerebrospinal fluid • Synovial, pleural, peritoneal, pericardial fluid, Amniotic fluid • Other body fluids contaminated with visible blood Exposure to Body Fluids Considered ‘Not at Risk‘ ( Unless these Fluids Contain Visible Blood ) • Tears • Sweat • Urine and faeces • Saliva • Sputum • Vomitus
  • 59. Post-exposure Prophylaxis……cont’d… • Blood transfusion • Perinatal (without any intervention) • Sexual intercourse • Vaginal • Anal • Oral • Injecting drugs use • Needle Stick exposure • Mucous membrane splash to eye, oro-nasal HIV transmission risk by different routes (WHO data) Exposure Route HIV Transmission Rate > 98% 20 - 40% 0.1–10% 0.05-0.1 0.065–0.5% 0.005–0.01% 0.67% 0.3% 0.09% Note: Comparative risk after needle-stick injury for HBV is 9% to 30% and for HCV is 1% to 1.8%
  • 60. Post-exposure Prophylaxis……cont’d… Exposed Person Regimen for PEP Alternate Regimen Adolescents and Adults (>10 yrs and >30 kg) TLD TL + Lopinavir/Ritonavir Children (>6 yrs and <10 yrs and >20 kg) ZLD Children (<6 yrs and <20 kg) Zidovudine + Lamivudine + Lopinavir/ritonavir if Hb < 9 gm/dl Abacavir+ Lamivudine + Dolutegravir if Hb < 9 gm/dl Abacavir+ Lamivudine + Lopinavir/ ritonavir Duration of PEP is 28 days, regardless of PEP regimen Check for HIV-Ab after 6 weeks, 3 months and 6 months PEP must be initiated ideally within 2 hrs and preferably within 72 hours
  • 61. JSS ART Statistical data as on 1-12-2022 Pre-ART Registered 1911 Started on ART 1749 Alive on ART 1162 ANC’S on ART 02 CLHIV 10 HIV-TB co-infection 09 From 1st December2012
  • 62. Key Points... • Adherence to ART is the key. • ART is not an emergency. • First treat ongoing opportunistic infections. • TLD is the most commonly used regimen. • Prevention of MTCT is of utmost importance. • PEP should be taken as early as possible.

Editor's Notes

  1. Diagnosis of HIV ICTC
  2. Choice of testing methods
  3. HIV I and HIV II
  4. Goals of ART
  5. WHO Clinical Staging