Dose Elimination Adverse effects
300 mg BD Glucuronidation
Anemia, neutropenia, bone
marrow suppression, GI
intolerance, headache, insomnia,
myopathy, lactic acidosis, skin
and nail hyperpigmentation
BD, or 300
unchanged in the
Headache, fatigue, rashes
nausea, anorexia, abdominal pain
Renal (renal failure
with a Fanconi’s-
Bone demineralization, nausea,
flatulence, abdominal discomfort,
loose motions and headache
• All NRTIs inhibit cellular DNA polymerases including DNA polymerase-
beta and mitochondrial DNA polymerase- gamma.
• Accumulation of ROS, decreased tissue oxidative respiration, and
increase in anaerobic respiration, resulting in increased production of
lactic acid as a byproduct
• C/F :Hepatic steatosis, lactic acidosis, myopathy, peripheral
neuropathy, pancreatitis and loss of peripheral adipose tissue
• Discontinuation with supportive management of acidosis and end-
• Progressive loss of subcutaneous adipose tissue, approximately 6
months after initiation
• maintenance of muscle mass and stable or increasing visceral
• associated with dyslipidemia, T2DM
• thymidine analog NRTI zidovudine and stavudine
• Discontinuation or substitution
Dose Elimination Adverse effects
600 mg OD on
rash – common, often mild
CNS (insomnia, dizziness and
vivid dreams to frank
psychosis and depression),
first 2 weeks after initiation.
raising to 400
mg daily after
2 weeks of
Rash is common, rarely SJS
Hypersensitivity reaction and
hepatotoxicity(higher CD4+ T-
DRUG–DRUG INTERACTIONS WITH NNRTIS
• Methadone replacement
therapy - opiate addiction
• Methadone metabolism is
increased when co administered
with efavirenz or nevirapine
• methadone withdrawal,
• buprenorphine, an alternative
opiate substitute, are also
• Rifampicin, a potent inducer of
the CYP450 enzyme system
• Decrease the conc. of efavirenz
• Recommending an increase in the
does of efavirenz from 600 mg
daily to 800 mg daily in patients
weighing over 60 kg when co
administered with rifampicin
• nevirapine with rifampicin-
increased rates of virological
Name Composition Dose Elimination Adverse effects
100 mg once or
the PI to be
3A isozymes & to a
lesser extent by
Common: GI (diarrhea,
600 mg twice a
mg twice daily)
with approx. 7% of
the drug eliminated
through the kidney
Hepatotoxicity, skin rash
moiety), diarrhea, nausea,
200 mg Lopinavir/ 50
mg Ritonavir Fixed
2 tablets twice daily
lipid profiles, glucose
300 mg daily with
100 mg ritonavir /
400 mg without
via CYP3A4 and is
also a potent
inducer of P-gp in
the enteric lumen
• Indinavir -tolerability issues and heavy pill burden
CYP3A4 system and is dosed at 800 mg twice daily with ritonavir
Principal toxicities - renal dysfunction secondary to crystalopathy,
(crystalluria, nephrolithiasis, and renal angle pain)
Hydration of 150 ml/ hr
• Nelfinavir is another PI that is no longer recommended- lack of
potency and intolerance (diarrhea)
• high total, LDL, TGL and decreased HDL cholesterol.
• More with LPV/r
• Associated with increased insulin resistance and diabetes.
• partially reversible upon switching away from PIs
• Use of lipid lowering agents has limited benefit.
Cardiovascular disease and Myocardial
• Indinavir and LPV/r
• risk persisted after correction for dyslipidemia
• dyslipidemia induced by antiretroviral exposure is thought to play a
• Also seen in Abacavir (inflammation and platelet dysfunction giving
rise to prothrombotic states)
• Allosteric reversible inhibitor of the CCR5 co-receptor.
• 150 mg and 300 mg tablet with variable dosing
• Metabolized by CYP3A4 with P-gp transportation in addition to
significant renal elimination(25%)
• No cross resistance with other classes
• Virologic failure may be related to emergence of CXCR4 tropic virus or
resistant mutations within CCR5-tropic virus(V3 loop)
• Large peptide comprised of 36 amino acids,
• Inhibits fusion by binding to gp41
• subcutaneous injection dosed at 90 mg twice daily
• Poor CNS penetration
• Resistance can rapidly develop, No cross resistance with other classes
• The major treatment limiting side effect is injection site reactions
• IgG4 humanized Mab, Under phase 3 study
• Binds epitope in domain 2 of CD4
• IV infusion (150mg/ml) or SC inj
• single-loading dose infusion of IBA 2,000 mg over 30 min
followed by a maintenance dose of IBA 800 mg IV over 15
min every 2 weeks.
• AE : More common: Rash, diarrhoea, headache, nausea,
dizziness, depression ; Less common (more
severe): Immune reconstitution inflammatory syndrome
(IRIS), hypersensitivity reaction
inhibition of HIV integrase
- “post-antibiotic” effect”
myopathy is a
currently the preferred
drug in the first-line and
also in second-line
primarily by UDP-
e (UGT) 1A1 and
Selectively inhibits strand
transfer reaction by
binding to Magnesium
and emtricitabine to
produce a four-drug
FDC—the “Quad” pill
• Selective inhibitor of CYP3A4
• pharmacological enhancer of PI and Elvitegravir
• Help replace ritonavir especially in HAART
• Adv : Lack of antiviral activity and decreased dyslipidemia
• Highly water soluble
• Mild increase in serum creatinine with unchanged creatinine
• second-line NNRTI (Phase III trials)
• Strong binding properties and conformational flexibility
• Metabolism : CYP3A4 enzyme activity and is slowly metabolized in
human hepatocytes through glutathione-dependent conjugative
• oral bioavailability is significantly increased with food
• The two phase III clinical trials, ECHO and THRIVE, compared
rilpivirine with efavirenz when used with a NRTI backbone = non-
inferior virological efficacy with rilpivirine
Indications for ART
Clinical Category CD4+ cell count Plasma HIV RNA Recommendations
AIDS defining illness
or severe symptoms
Any value Any value Start HAART
Asymptomatic CD4+ <200 cells/mm3 Any value Start HAART
Asymptomatic CD4+ 200-350
CD4+ >350 cells/mm3 >100,000
Asymptomatic CD4+ >350 cells/mm3 <100,000
Evaluation before initiating
• Complete history and physical examination
• Ophthalmological examination
• CBC, blood glucose and lipid profile
• CD4+ cell count
• Plasma HIV RNA measurement
• Other : VDRL, Mantoux test, Toxoplasma IgG serology, CXR
1st line (NACO)
• Triple drug combination from two different classes of ARVs.
• NRTI backbone, preferably Non-Thymidine (Tenofovir plus
Lamivudine) and one INSTI, preferably DTG.
• The preferred first-line ART regimen for all PLHIV with age >10 years
and weight >30kg is as follows:
• 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)
Antiretroviral drug combinations to be avoided
1.Zidovudine + stavudine: Pharmacodynamic antagonism
2.Stavudine + didanosine: Increased toxicity (neuropathy, lactic
3. Lamivudine + didanosine: Clinically not additive
Changing a failing regimen
• An ART regimen is considered to have failed when:
oPlasma HIV-RNA count is not rendered undetectable (<50 copies/μl)
within 6 months therapy.
oRepeated detection of virus in plasma after initial suppression to
undetectable levels despite continuation of the drug regimen.
oClinical deterioration, fall in CD4 cell count, serious opportunistic
infection while continuing drug therapy.
• Failed regimen should be changed entirely
Perinatal HIV prophylaxis
• Highest risk (>2/3rd) of transmission is during the birth process
• Current recommendation : all HIV positive women, not on ART, should
be put on the standard 3 drug ART, continued through delivery and
into the postnatal period.
• Zidovudine + Lamivudine + Nevirapine
• If not on ART, Zidovudine (300 mg BD) started during 2nd trimester
and continued through delivery to postnatal period, with treatment
of the neonate for 6 weeks, reduce mother-to-child transmission by
• Breastfeeding is contraindicated
Pre exposure prophylaxis
As of January 2019, FDA has approved three medications as PrEP for HIV:
1.Truvada (tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg)
1. preferred oral regimen for daily or on-demand dosing.
2.Descovy (tenofovir alafenamide 25 mg/emtricitabine 200 mg)
1. alternative oral regimen used only in daily dosing for cisgender MSM and
2. Descovy is not approved for use by cis-gender women and is not for use during
3.Apretude (Long-acting injectable cabotegravir 600 mg)
1. preferred regimen.
2. Apretude is generally not an option during pregnancy.
3. Not all clinical settings are prepared to administer long-acting injectable PrEP.
Effective in decreasing MTCT of HIV
DI : Ganciclovir, Paracetamol, Azoles.
Anti - HIV 1 & 2, Hep B
For chronic hepatitis B—100 mg OD
Concentrations are increased in patients with moderate to severe renal impairment.
Tenofovir Disoproxil Fumarate
Bypasses rate-limiting phosphorylation, hydrolyzed by plasma esterases and metabolized intracellularly to the active triphosphate form.
Poor CSF penetration
Longer half-life, once-daily dosing, resulted in its use in fixed-dose combination (FDC) form with TDF (Truvada®) and with TDF and efavirenz (Atripla®).
Ineffective in viruses harboring a resistance mutation in the reverse transcriptase gene.
Increased risk of myocardial infarction in some studies
Good CSF penetration
First-line HAART regimes for ARV-naive patients
Highly protein bound (approx 99%), the free fraction penetrates the CSF
and may resolve without discontinuing.
Most commonly used NNRTI in India
Induces its own metabolism within the first 2 weeks of therapy and is.
DI : Antihistamines, antifungals.
FDA approved in January 2008 for treatment-experienced HIV-infected patients.
Decreases the Cmin of the protease inhibitor atazanavir, Increases concentrations of the protease inhibitor fosamprenavir.
Bioavailability - 60–80% and is almost entirely protein bound at 99%.
DI : HMG-Co A reductase inhibitors, Fluticasone and PDE inhibitors.
Approved for use in both antiretroviral naive and treatment-experienced patients
Absorption is dependent on P-gp protein transportation across the intestinal lumen and it is highly protein bound (approx 95%).
metabolized inhibits UDP-glucuronyl transferase - ↑ unconjugated bilirubin
combination with the NNRTI etravirine is not recommended as atazanavir exposure is signiicantly reduced & vice versa with Nevirapine
Poor CSF penetration
Susceptible to boosting with both ritonavir and cobicistat
Both HIV type 1 & 2
DI : Amodiaquine, Carbamazepine, Phenytoin and phenobarbital, Metformin, Rifampcin