Anti-retroviral drugs

Dr. Tejas K. Patel

Asst. Professor,
Department of Pharmacology,
GMERS Medical College, Gotri,
Vadodara
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Reverse
transcriptas
e inhibitors

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Protease
inhibitors

CCR5
inhibitors

Entry
inhibitors

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Integrase
inhibitors
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Targets for antiretroviral therapy

HIV reverse transcriptase enzyme
HIV protease enzyme
Newer targets
Fusion of viral envelope with membrane
of CD4 T lymphocytes
Chemokine receptor on host cells
HIV integrase enzyme
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Classification

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 Nucleoside reverse
transcriptase
inhibitors (NRTIs)

Zidovudine
Stavudine
Lamivudine
Abacavir
Didanosine

Non- Nucleoside
reverse
transcriptase
inhibitors (NNRTIs)
Efavirenz
Nevirapine

Nucleotide reverse
transcriptase
inhibitors (NtRTIs)
Tenofovir

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Pharmacovigilance

 Protease inhibitors

Saquinavir
Indinavir
Nelfinavir
Ritonavir
Lopinavir

Entry/fusion
inhibitors
Enfuvirtide

CCR5 inhibitors
Maraviroc

Integrase inhibitors
Raltegravir

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Pharmacovigilance

Nucleoside reverse
transcriptase inhibitors

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Zidovudine
Thymidine analogue
After phosphorylation (Zidovudine triphosphate)
interferes with the activity of reverse transcriptase
enzyme
Zidovudine incorporates in to proviral DNA

Inhibits proviral DNA synthesis

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 Important ADR
Anaemia
neutropenia

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Stavudine
Thymidine analogue
Important ADR
Peripheral neuropahty
Lipodystrophy
Lactic acidosis
Rarely pancreatitis

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Lamivudine
Deoxycytidine analogue
Most tolerated ARV drug
Part of all first line regimen of NACO

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Non-nucleoside reverse
transcriptase inhibitors
Nucleoside unrelated
compound

Nevirapine
Efavirenz

Directly inhibit HIV

RT enzyme
Only acts on HIV-1

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Pharmacovigilance

Non-nucleoside reverse
transcriptase inhibitors
Nevirapine

Efavirenz

Rifampicin induces
metabolism of
nevirapine

Rifampicin does not

induce metabolism of
efavirenz

Important ADR

Important ADR

Rashes, SJS
Hepatotoxicity
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Teratogenicty

Pharmacovigilance

Nucleotide reverse transcriptase

inhibitors (NtRTIs)
Tenofovir
Tenofovir diphophate incoprorates in to
proviral DNA chain & terminates its
synthesis
Well tolerated drug
Part of alternative first line regimen
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Protease inhibitors
Protease enzyme breaks polyprotein
in to functional viral protein
Last step in HIV replication

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Protease inhibitors
PIs binds to active site of protease enzyme

Interfere with its cleaving function

HIV infected cells produce immature noninfectious
viral progeny
Prevents further round of infection
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Drawbacks of Protease inhibitors

(PIs)
PIs induce as well as inhibit CYP450
enzymes
Complex and unpredictable drug interactions

Rifampicin indues metabolism of PIs

Short half life
Large table load (6-18 tablets daily)
Low acceptability & poor compliance

Used as a 2nd line regimen

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Anti-retroviral therapy

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ART requires by all HIV+ve patients

who are
Symptommatic
Asymptommatic with CD4 cell count
350 cells/l
Requiring treatment for HBV/HCV
Pregnant
With HIV nephropathy

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 NACO gives priority to HIV+ve

positive patients
In WHO clinical stage 3 & 4
Since 6-8 years ago
With H/o pulmonary TB or herpes zoster
Partners of AIDS pts
Children < 15 years of age

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Therapeutic regimens
At least 3 drug

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1/15/16

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Therapeutic regimens
At least 3 drug
No optimal Initial regimen
As per NACO
2 NRTI + 1 NNRTI
Lamivudine in all regimen
2nd NRTI can be zidovudine/ stavudine
NNRTI can be nevirapine/efavirenz

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Preferred 1st line regimen

Lamivudine + Zidovudine + Nevirapine

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Alternative first line regimen for

patients with
1. Hepatic dysfunction/ receiving
rifampicin
Lamivudine + Zidovudine + Efavirenz

2. Anaemia
Lamivudine + Stavudine + Nevirapine

3. Hepatic dysfunction/ receiving

rifampicin & anaemia
Lamivudine + Stavudine + Efavirenz
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4. Not able to tolerate Zidovudine/

Stavudine
Lamivudine + Tenofovir + Nevirapine
Lamivudine + Tenofovir + Efavirenz

5. Not able to tolerate Nevirapine/

Efavirenz
Lamivudine + Zidovudine + Tenofovir
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 Protease inhibitor for advanced cases

2NRTI + 1 PI
NRTI + NNRTI + PI

If drug toxicity develops

No dose modification should be tried
Entire regimen or offending drug should
be changed
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 Pregnancy does not contraindicate

ART
Lamivudine + Zidovudine + Nevirapine
Other safe drugs are Nelfinavir,
saquinavir

ART be continued during acute

opportunistic infection
Except in case of intolerance/toxicity

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 ART is considered failed when

Plasma HIV-RNA count is not rendered
undetectable within 6 months of therapy
(<50 copies/l)
Repeated detection of virus in plasma after
successful suppression
Clinical deterioration
Fall in CD4 count
Serious opportunistic infection while continuing
treatment

Failed regimen should be changed

entirely
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Post-exposure prophylaxis
For low risk patient
2 drug regimen
Zadovudine 300 mg + lamivudine 150
mg BD for 4 wks

For high risk patient

3 drug regimen
Zadovudine 300 mg + lamivudine 150
mg BD
Plus Indinavir 800 mg TDS for 4 wks
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