1. ANTIRETROVIRAL THERAPY
PRESENTER DR B ROHITH
MODERATOR DR VISHNU SHANKER SHUKLA
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2. GOALS OF ANTIRETROVIRAL THERAPY
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3. When to start ART
• The guidelines on when to start ART have evolved over the years
towards early and rapid initiation of ART.
• The current recommendation to TREAT ALL, regardless of the clinical
stage or CD4 count is in the National Programme since 2017.
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6. Targets of antiretroviral drugs
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7. Classification of antiretroviral drugs
• Entry Inhibitors (Chemokine (CCR5) co-receptor antagonist) and Fusion inhibitors
Block binding of HIV to the target cell.
• Nucleo(t)side Reverse Transcriptase Inhibitors (NRTIs) and Non-nucleoside Reverse Transcriptase
Inhibitors (NNRTIs).
Block the viral RNA cleavage and one that inhibits reverse transcriptase.
• Protease Inhibitors (PIs)
Block enzyme protease
• Integrase Inhibitors
Block the enzyme integrase, which helps in the proviral DNA being incorporated into the host cell
chromosome.
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8. Classes of ARV with examples
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9. 1.FUSION INHIBITOR (FI)
 ENFUVIRTIDE (T-20)
2.CCR5 ENTRY INHIBITOR
 MARAVIROC
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10. Fusion inhibitors
• Enfuvirtide –
• First approved entry inhibitor, not available now.
Dose : 90 mg SC bid
ADRs : Injection-site reactions (eg, pain, erythema, induration, nodules) diarrhoea, nausea,
fatigue, hypersensitivity reactions, increased rate of bacterial pneumonia.
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11. Entry inhibitor
• Maraviroc –
CCR5 antagonist
150 – 600 mg bd (PO)
Hepatotoxicity, fever, abdominal pain, cough, dizziness, rash, musculoskeletal symptoms
• Fostemsavir –
Recently approved attachment entry inhibitor for multidrug resistant HIV in adults.
• Ibalizumab
Anti CD4 monoclonal antibody
Single loading dose of 2000mg followed by 800mg every 2 weeks
Rash, nausea, diarrhoea
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12. 3.NUCLEOSIDE REVERSE
TRANSCRIPTASE INHIBITOR
(NsRTI)
 ZIDOVUDINE ( AZT/ZDV)
 STAVUDINE (D4T)
 LAMIVUDINE(3TC)
 ABACAVIR (ABC)
 DIDANOSINE (ddl)
 ZALCITABINE (ddC)
 EMTRICITABINE (FTC)
4.NUCLEOTIDE REVERSE
TRANSCRIPTASE INHIBITOR
(NtRTI)
 TENOFOVIR (TDF) 12

13. Nucleo(t)side Reverse Transcriptase Inhibitors (NRTIs)
• First agents available for HIV Infection.
• Less potent than NNRTIs and PIs
• They act by incorporating themselves into the DNA of the virus,
thereby stopping the building process. The resulting DNA is
incomplete and cannot create new viruses.
• Nucleotide analogues work in the same way as nucleosides, but they
have a non-peptidic chemical structure.
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16. 5.NON-NUCLEOSIDE
REVERSE
TRANSCRIPTASE
INHIBITORS
(NNRTI)
 NEVIRAPINE(NVP)
 EFAVIRENZ(EFV)
 RILPIVIRINE (RPV)
 ETRAVIRINE (ETV)
 DELAVIRDINE(DLV)
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17. Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) stop HIV
production by binding onto the reverse transcriptase and preventing
the conversion of RNA to DNA.
• These drugs are called ‘non-nucleoside’ inhibitors because, even
though they work at the same stage as nucleoside analogues, as
chain terminators, they inhibit the HIV reverse transcriptase enzyme
by directly binding to it.
• Have potent activity against HIV-1 and are part of preferred initial
regimens.
• Efavirenz, confers most significant inhibition of viral infectivity,
currently not recommended because of its CNS side effects.
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19. 6. INTEGRASE
INHIBITORS
 RALTEGRAVIR
(RGV)
 ELVITEGRAVIR
(EVG)
 DOLUTEGRAVIR
(DTG)
 BICTEGRAVIR
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20. Integrase inhibitors
• Integrase inhibitors are a class of ART drugs designed to block the
action of integrase, a viral enzyme that inserts the viral genome into
the DNA of the host cell.
• Since integration is a vital step in retroviral replication, blocking it can
halt further replication of the virus.
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22. 7. PROTEASE
INHIBITORS (PI)
 SAQUINAVIR (SQV)
 RITONAVIR (RTV)
 NELFINAVIR(NFV)
 AMPRENAVIR(APV)
 INDINAVIR (INV)
 LOPINAVIR (LPV)
 FOSAMPRENAVIR
(FPV)
 ATZANAVIR (ATV)
 TIPRANAVIR (TPV)
 DARUNAVIR (DRV) 22

23. Protease inhibitors
• Protease inhibitors (PIs) work at the last stage of the viral
reproduction cycle.
• They prevent HIV from being successfully assembled and released
from the infected CD4 cell.
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26. What to start???
•INSTI + 2 NRTIS
DOLUTEGRAVIR (DTG50mg)+ TENOFOVIR ALAFENAMIDE
(TAF) OR TENOFOVIR DISOPROXIL FUMARATE (TDF
300mg)
+LAMIVUDINE (3TC 300mg)
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27. Dolutegravir based regimen is preferred over
Efavirenz based regimen
• Because of better tolerability and lesser resistance development with DTG,
effective against HIV2
• According to lancet study , DTG lowers viral copy load to <50 copies per ml
in median of 28 days compared to 84 days of Efavirenz.
• According to latest guidelines and BOTSWANA TSEPAMO study ,
prevalence of neural tube effects with DTG has reduced during conception.
• DTG appears to be safe when started later in pregnancy: after the period of
risk of neural tube defects, after the first trimester.
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28. Advantages of DTG over EFZ
• Lower potential for drug interactions
• A shorter median time to viral suppression
• Higher genetic barrier to developing drug resistance
• Low cost
• Low dose
• Long half life
DTG in TB
• Increase the dose to 50mg bd when given with rifampicin
• Because of drug interaction with rifampicin
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29. DIETARY CONSIDERATIONS FOR TAKING DTG
• DTG could be taken at a fixed time everyday without regard to meals.
• DTG interact with calcium and iron and few other medicines.
• If these are prescribed to patient, DTG can be taken 2 hours before or 6
hours after antacids ( which contain magnesium/ aluminium ) or
laxatives, sucralfate, oral supplements containing iron or calcium
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30. ALTERNATIVE REGIMENS
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31. Monitoring of patients on ART
*CD4 Count : 1. CD4 testing should be done every 6 months till CD4 count
reaches greater than 350 cells/ cmm and viral load is less than 1000
copies/ml 31

32. • NACO HAS DEFINED STABLE PATIENTS AS THOSE WHO
• Are on ART for atleast one year
• Have good treatment adherence
• An increasing CD4 count and
• Are devoid of any active Opportunistic infections
Such patients can be advised for visit every 3 months
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33. Lab investigations to be done in patients on ART
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34. What to Expect in the First Six Months of
Therapy?
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35. Immune Reconstitution Inflammatory Syndrome
• “The worsening of signs and symptoms due to known infections” or
“the development of disease due to occult infections that result from
an inflammatory response by a reinvigorated immune system
following the initiation of ART.”
• It occurs in 10% to 30% of patients initiating ART, usually within the
first 4–8 weeks. However, late IRIS can be observed up to 6 months of
initiating ART.
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36. Risk factors for IRIS-
1. CD4 count below 100 cells/ cumm before starting ART or lower
CD4:CD8 ratio
2. Rapid initial fall in HIV viral load due to therapy.
3. Shorter interval between OI therapy initiation and ART initiation
4. Severity of TB disease , especially high pathogen burden
5. Male sex
6. Younger age
7. Genetic susceptibility
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37. • Management of IRIS-
• IRIS is generally self-limiting and interruption of ART is rarely indicated.
• Short term therapy with corticosteroids or NSAIDs – Prednisolone in
dose of 1.5 mg / kg orally for two weeks followed by 0.75 mg/ kg orally
for two weeks and then tapered off
• Antibiotic coverage
• Temporary cessation of ART must be considered, only if potentially life-
threatening forms of IRIS develop.
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38. Opportunistic infections and ART
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41. Prevention of opportunistic infections
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45. Decision to start PEP following exposure
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48. POST EXPOSURE PROPHYLAXIS
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49. ART IN SPECIAL SITUATIONS
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52. ART IN PREGNANCY
• Test as soon as pregnant
• Repeat in 3rd trimester in high risk patient
• All HIV positive pregnant women including those presenting in labour
and breast feeding should be ihitiated in a triple drug ART regardless
of CD4 count and clinical stage for preventing transmission and
continue lifelong
Tenofovir (TDF ) + lamivudine
(3TC) + Efavirenz ( EFV)
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53. Intrapartum
• Continue ART
• IV zidovudine if HIV RNA >1000 copies/ml near delivery
• Cesarean section delivery at 38 weeks if HIV RNA > 1000 copies/ml
• If HIV RNA <1000, early termination of pregnancy or Cesarean section
has no added benefits
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54. RISK OF HIV TRANSMISSION FROM MOTHER TO
CHILD WITH ARV INTERVENTIONS
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55. POSTPARTUM
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Duration of nevirapine prophylaxis should be extended to 12 weeks
If duration of ART in pregnant mother falls short 4 weeks during pregnancy and before deliver or reporting
at time of labour or after delivery ,if not already on ART

56. Infants testing
• HIV RNA or DNA Nucleic acid test (NAT) are recommended
• Non breast fed infants – 2 negative test at 1 month and 4 month age- consider negative.
• Breastfeeding not recommended
• If breastfeeding, testing every 3 months (NAT)
• 1,3 and 6 months after cessation of breastfeeding
• DNA PCR @ 6 months age or 6 weeks after cessation of breast feeding ( NACO 2018)
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57. Co-INFECTION OF TUBERCULOSIS & HIV
• Selection of TB- preventive treatment for individuals with HIV and
Latent tuberculosis infection (LTBI) should be based on individual’s
ARV regimen
With daily isoniazid 300mg with pyridoxine 50mg for 6 or 9 months ,
any ARV regimen can used
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58. • All patients with HIV and active TB who are not on antiretroviral
therapy ( ART) should be started on ART as follows:
• CD4 T lymphocyte (CD4) cell counts <50 cells/mm3: Initiate
ART as soon as possible, but within 2 weeks of starting TB
treatment.
• CD4 counts ≥50 cells/mm3: Initiate ART within 8 weeks of
starting TB treatment.
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59. • During pregnancy, regardless of CD4 count: Initiate ART as early
as feasible, for treatment of the person with HIV and to prevent
HIV transmission to the infant.
• With TB meningitis: When initiating ART early, patients should be
closely monitored, as high rates of adverse events and deaths
have been reported in a randomized trial. ART should be delayed at
least 4 weeks (and initiated within 8 weeks) after treatment for TB
meningitis is initiated. Corticosteroids should be considered for
adjuvant treatment of TB meningitis.
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60. TB DIAGNOSED WHILE A PATIENT IS RECEIVING
ART?
• ART should be continued when TB is diagnosed in a patient
receiving ART but drug interactions should be assessed
• Rifampicin interacts with dolutegravir . Hence, PLHIV while
Rifampicin containing ATT should be given
DTG 50 mg twice a day.
• In such PLHIV, an additional dose of DTG 50mg should be
continued 2 weeks after completion of TB treatment and then OD
dose be given.
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61. ART FAILURE
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62. Second line ART
• A new class of ARV , a Ritonavir boosted PI ( Atazanavir / ritonavir or
Lopinavir/ ritonavir)
• Supported by atleast one new and unused NRTI (Zidovudine or
Tenofovir) or integrase inhibitor ( dolutegravir or raltegravir)
• Continued Lamivudine administration ensures reduced viral fitness
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