HAART, or highly active antiretroviral therapy, involves using a combination of antiretroviral drugs to treat HIV. The goals of ART include increased survival, improved quality of life, reduction of viral load, immune reconstitution, and limiting drug toxicity while maintaining treatment options and adherence. Commonly used drug classes include NRTIs, NNRTIs, integrase inhibitors, and protease inhibitors. Treatment involves monitoring viral load, CD4 count, adverse effects, and potential treatment failure or immune reconstitution inflammatory syndrome. Guidelines provide recommendations on treatment initiation and first, second, and third-line regimens for both adults and children.

1. HAART IN TREATMENT OF HIV
MODERATOR –Dr VIJAY PALIWAL SIR
PRESENTED BY-Dr AATISH TAMTA

2. HAART
• HIGHLY ACTIVE ANTIRETROVIRAL THERAPY
• Introduce in 1990 to describe the effectiveness of combine drug
therapies used to treat HIV.
• Today the term HAART replaced by Combination antiretroviral
therapy or simply ANTIRETROVIRAL THERAPY (ART).

3. GOALS OF ART
• Clinical goals: Increased survival and improvement in quality
of life.
• Virological goals :Greatest possible sustained reduction in viral
load.
• Immunological goals: quantitative and qualitative Immune
reconstitution.
• Therapeutic goals: Rational sequencing of drugs in a manner
that achieves above goals while maintaining future treatment,
options, limiting drug toxicity and facilitating adherence.
• Preventive/epidemiological goals: Reduction of HIV
transmission by suppression of viral load.

4. CLASSES OF ARV DRUG

5. TARGETS OF ANTIRETROVIRAL DRUGS

6. COMMONLY USED NRTIS
Generic Name Dose Adverse effects
Tenofovir (TDF) 300 mg OD Renal toxicity, bone demineralization
Zidovudine
(ZDV, AZT)
300 mg BD Anaemia, neutropenia, bone marrow
suppression, gastrointestinal intolerance,
headache, insomnia, myopathy, lactic
acidosis, skin and nail hyper pigmentation
Lamivudine (3TC) 150 mg BD or 300 mg OD Minimal toxicity, rash
Abacavir (ABC) 300 mg BD
or 600 mg OD
Hypersensitivity reaction in 3 to 5% (can
be fatal), fever, rash, fatigue, nausea,
vomiting, anorexia, respiratory
symptoms (sore throat, cough, shortness
of breath)

7. COMMONLY USED NNRTIS
Generic Name Dose Adverse Effects
Efavirenz
(EFV)
.
600 mg OD (bed time to
decrease CNS side-effects)
Avoid taking after high fat meals
CNS symptoms (dizziness, somnolence,
insomnia, confusion, hallucinations,
agitation) and personality change. Rash
occurs, but less common than NVP
Nevirapine
(NVP)
200 mg OD for 14 days,
followed by 200 mg BD
Hepatitis (usually within 12 weeks),
Skin rash , including Stevens Johnson
syndrome (SJS) and Toxic Epidermal
Necrolysis (TEN).

8. INTEGRASE INHIBITORS

9. PROTEASE INHIBITORS
Generic
Name
Dose Adverse Effects
Atazanavir/
ritonavir
(ATV/r)
300 mg Atazanavir + 100 mg
Ritonavir OD
Unconjugated hyperbilirubinaemia, lipid
abnormality, hyperglycaemia, fat
maldistribution, nephrolithiasis,
cholelithiasis, PR prolongation
Lopinavir /
ritonavir
(LPV/r)
Heat stable tablets 200 mg
Lopinavir/50mg Ritonavir Fixed
dose tablet 2 tablets BD
Diarrhoea, nausea, vomiting, abnormal
lipid profiles, glucose
intolerance
Darunavir
(DRV)
600 mg twice a day (when used
with Ritonavir 100 mg BD
Hepatotoxicity, skin rash (10%),
diarrhoea, nausea, headache,
hyperlipidemia, serum transaminase
elevation, hyperglycaemia
Ritonavir
(RTV)
100 mg BD gastrointestinal (diarrhoea, nausea,
vomiting, abdominal pain (upper and
lower), rarely neurological disturbances
(including paraesthesia)

10. FIRST LINE ARV REGIMENS GUIDELINES ( 2 NRTI + 1 INSTI)
Tenofovir (TDF 300 mg) + Lamivudine (3TC 300 mg) + DOLUTEGRAVIR (DTG 50 mg)
regimen (TLD) as FDC in a single pill once a day (at a fixed time every day as per patient’s
convenience)

11. Laboratory monitoring of individual ARV drugs

12. Considerations before Initiation of ART
• All confirmed HIV cases should be referred to the ART centre
for registration in HIV care, treatment preparedness, counselling
and timely ART initiation.
• Informed consent should be obtained from the patient or from
the caregiver , before initiating HIV care and ART.
• Opportunistic infections should be treated or stabilized before
commencing ART except Mycobacterium Avium Complex and
Progressive Multifocal Leukoencephalopathy, in which
commencing ART may be the preferred treatment.
• Caregivers must be counselled and trained to support treatment
adherence, follow-up visits and shared decision-making.

13. • INDICATION FOR STARTING OF ART
- Irrespective of CD4 cell count

14. Monitoring and follow-up schedule for patients on ART

15. PPTCT and ART in Pregnant Women
Goal and Objectives of PPTCT Services in India
• Goal: elimination of paediatric HIV and improve maternal,
newborn and child health and survival in of HIV patients.
• Objectives:
1. Detect >90 % HIV infected pregnant women in India.
2. Provide access to comprehensive PPTCT services to > 90 % of
the detected pregnant women.
3. Provide access to early infant diagnosis to >90 % HIV exposed
infants.
4. Ensure access to anti-retroviral drug (ARVs) prophylaxis or
Anti-Retroviral Therapy (ART) to 100 % HIV exposed infants.
5. Ensure > 95 % adherence with ART in HIV infected pregnant
women and ARV/ ART in exposed children.

16. ART REGIMENS IN BREASTFEEDING AND PREGNENT
WOMEN WITH HIV

17. • HIV risk assessment of infants born to HIV-infected
mothers and infant ARV Prophylaxis options

18. INDICATIONS TO START ART IN CHILD
1). Clinical criteria ( infant/ child confirmed case of HIV ).
• Paediatric clinical stage 4 : T/T irrespectively
• Paediatric clinical stage 3 and if child is > 18 months : T/T
guided by CD4 counts and decrease platelet counts .
• Paediatric clinical stage 2: T/T guided by CD4 count /TLC .
• Paediatric clinical stage 1: T/T guided by CD4 count if CD4 count
not available don’t start ART.

19. 2). Clinical criteria in symptomatic child with unconfirmed HIV
infection
• < 18 month age and p24 Ag/ virological tests not available
presumptive diagnosis of stage 4 done by :
• HIV exposure confirmed by antibody tests.
• >2 symptoms:
 Oral thrush
 Severe pneumonia
 Severe wasting/malnutrition
 Severe sepsis
 CD4%: <25%
• Recent HIV related death of mother.
• Advanced HIV disease in mother

20. • First-line ART regimens for infants and children with
HIV-1 and HIV-2 infection

21. MONITORING AND FOLLOWUP IN CHILDERN
Clinical monitoring
• Monthly clinical evaluation: growth, development and nutrition
• TB screening: 4 symptoms screening (4S screening)
• Treatment adherence evaluation: at every visit
• For adverse reactions of ART / Opportunistic infections, drug
interactions.
• For IRIS (Immune Reconstitution Inflammatory Syndrome)
Immunological monitoring
• CD4 count (%): every 6 months for children upto 5 years. After
that follow adult guidelines
Virological monitoring
• Viral load testing: at 6 months and 12 months after ART
initiation and then once every year

22. ART IN TB PATIENTS ADULT
ART in relation to initiation of TB treatment
In HIV-TB co infected patients:
• Start ART regardless of the CD4 count
• Start ATT first, initiate ART as soon as TB treatment is tolerated
(between 2 weeks and 2 months).
• Modification of ART: In PLHIV who are already on ART at the
time of TB diagnosis, modification of ART needs to be done to
maintain optimal efficacy of ATT as well as ART.
• Efavirenz is the preferred drug, if Rifampicin used for TB
co-infection.
• In children aged < 3 years and in children weighing < 10 kg,
Super-boosted Lopinavir/ritonavir given instead of
efavirenz.

23. Recommendations if TB is diagnosed in patients already
receiving ART

24. ART WITH TB IN CHILD

25. ART WITH HEPETITIS B INFECTION
The indications for anti-viral treatment in Chronic Hepatitis B
(CHB) :
• in all age groups if clinical evidence of compensated /
decompensate cirrhosis, regardless of ALT, HBeAg status, HBV
DNA levels.
• For adults with CHB, who do not have clinical evidence of
cirrhosis, but are aged > 30 years and have persistently
elevated ALT levels and evidence of high-level HBV replication
(HBV DNA > 20,000 IU/ ml) regardless of HBeAg status
• If HBV DNA testing is unavailable but patients have
persistently elevated ALT, treat for Hepatitis B regardless of
HBeAg status

26. • When to start ART: All persons diagnosed with HIV infection
should be initiated on ART regardless of CD4 count or WHO
clinical staging or age group or population sub-groups
• Choice of regimen: Nucleoside analogues with dual activity
against both the viruses such as 3TC and TDF should be included
in the first-line ART regimen .
• Preferred Regimen: TDF +3TC +EFV (TDF may be replaced by
AZT* in case of TDF toxicity or contraindications)
• Second Line Regimen: TDF and 3TC should be continued as part
of the second-line ART following initial ART failure, even if it was
used in the first-line regimen.

27. TREATMENT FAILURE
Failure Definition Comments
Virological failure Plasma viral load >1000
copies/ ml.
Taking ART for at least 6 months
before it can be determined that a
regimen has failed
Immunological
failure
CD4 count falls to the
baseline (or below)
or
Persistent CD4 levels
<100 cells/cumm
or
50% fall from “on
treatment” peak level
Concomitant or recent infection may
cause a transient decline in the CD4
cell count.
persistent CD4 counts of <50
cells/cumm after 12 months of ART to
be more appropriate

28. Failure Definition Comments
Clinical failure New or recurrent clinical event
indicating severe
immunodeficiency (WHO clinical
stage 4 condition) after 6 months
of effective treatment
.
The condition must be differentiated
from IRIS. Some WHO clinical stage 4
conditions (lymph node TB,
uncomplicated TB pleural disease,
oesophageal candidiasis, recurrent
bacterial pneumonia) may not
indicate treatment failure.
For adults, certain WHO clinical stage 3
conditions(pulmonary TB and severe
bacterial infections) may also indicate
treatment failure

29. Comprehensive second-line ART regimens for PLHIV failing on
first-line ART

30. • Third-line ART regimens

31. 2ND LINE ART IN CHILD

32. Third-line ART regimes in CLHIV

33. Immune reconstitution inflammatory
syndrome (IRIS)
• This is paradoxical worsening in clinical status
after ART initiation despite improved
immunity .
• It is an inflammatory response against
infectious agents which may or may not
diagnosed at time of starting ART .
• Occurs in pt’s with lower CD4 counts and rapid
decrease in viral load .

34. • Occurs in first 6 weeks of starting of ART ,
sometimes several month later .
*criteria for IRIS diagnosis
1) Response to ART (at least one log10 copies
decrease in HIV RNA )
2) Clinical deterioration of an infectious
condition
3) Symtoms cannot be explained by the
expected clinical course .

35. • The pathogen that are most usually implicated
are-
- M. avium complex
- M. tuberculosis
- Cmv , HCV , VZV , HBV ,JC , HSV
- Cryptococcus
- PCP

36. • LABORATORY FINDING –
- CD4 cell increase , viral load decrease
TREATMENT OF IRIS
1) First treat suspecting pathogen
2) Specfic agents – judicious use of NSAIDS ,
steroid

37. • THANK YOU