I. Antiretroviral classifications:
1) Nucleoside (and nucleotide) reverse transcriptase inhibitors (NRTIs):
Mechanism of action: Inhibit viral replication by acting as nucleoside analogues and interfering with the
DNA polymerase function of the viral reverse transcriptase. They are incorporated into the growing DNA
chain, leading to premature chain termination.
2) Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
Mechanism of action: They are noncompetitive inhibitors of reverse transcriptase and cause inhibition of
enzyme function by binding at sites distinct from the nucleoside-binding site.
3) Protease inhibitors (PIs)
Mechanism of action: Several viral proteins, including those that form the protein components of the viral
core, as well as protease itself, reverse transcriptase, and integrase, are synthesized as polyproteins that
require cleavage by the viral protease to produce mature proteins. Protease inhibitors block the necessary
cleavage of these polyproteins in the late stages of the viral replicative cycle, causing the production of
immature, defective viral particles.
4) Fusion Inhibitors
Mechanism of action: Inhibits the fusion of HIV-1 virus with CD4 cells by blocking the conformational
change in gp41 required for membrane fusion and entry into CD4 cells.
II. Antiretroviral Regimens Basics:
1) Base and Backbone: Regimens should have at least three antiretroviral medications. They are
described as having both a base and a backbone. The base is either an NNRTI or a PI (or boosted PI
[with Ritonavir]). The backbone typically consists of two NRTIs. Regimens consisting of three NRTIs
are rarely used because they have higher rates of virologic failure than NNRTI- or PI-based regimens.
Two boosted PI's are sometimes used as the base in patients on salvage regimens.
2) Boosting: Regimens containing protease inhibitors often will utilize the strategy of "boosting." Ritonavir
(RTV, Norvir) is an extremely potent inhibitor of PI metabolism via the P450 (CYP3A4) pathway.
Therefore it is often used at a low dose to increase (boost) the drug level and duration of another PI. RTV
in a boosted regimen is abbreviated with a small "r" as in LPV/r (Lopinavir + Ritonavir, Kaletra [brand
name]).
III. Summary of Antiretroviral Agents:
NRTIs
1) Abacavir (ABC, Ziagen)
Combo forms: Trizivir (ABC+ ZDV + 3TC), Epzicom (ABC + 3TC)
Dosing: 300 mg BID or 600 mg Daily
Adverse Effect: Hypersensitivity reaction
Hint: Ziagen is a part of TriZivir and EpZicom
2) Didanosine (ddI, Videx)
Dosing: 400 mg Daily (>60kg) or 250 mg Daily (<60kg)
Adverse Effects: Pancreatitis, Peripheral neuropathy, Lactic Acidosis
3) Emtricitabine (FTC, Emtriva)
Combo forms: Truvada (FTC + TDF)
Dosing: 200 mg Daily
Adverse Effects: Lactic Acidosis
4) Lamivudine (3TC)
Combo forms: Combivir (3TC + ZDV), Trizivir (ABC+ ZDV + 3TC), Epzicom (ABC + 3TC)
Dosing: 150 mg BID or 300 mg Daily
Adverse Effects: Lactic Acidosis
5) Stavudine (d4T, Zerit)
Dosing: 40 mg BID (>60kg) or 30 BID (<60kg)
Adverse Effects: Peripheral neuropathy, Lipodystrophy, Lactic Acidosis (higher incidence than other
NRTIs), Pancreatitis, Ascending neuromuscular weakness (rare), Hyperlipidemia
6) Tenofovir (TDF, Viread)
Combo forms: Truvada (TDF + FTC)
Dosing: 300 mg Daily
Adverse Effects: Renal insufficiency, Lactic Acidosis
7) Zalcitabine (ddC, Hivid) [NOTE: Rarely prescribed]
Dosing: .75 mg TID
Adverse Effects: Peripheral neuropathy, Stomatitis, Lactic Acidosis, Pancreatitis
8) Zidovudine (AZT, ZDV, Retrovir)
Combo forms: Combivir (3TC + ZDV), Trizivir (ABC+ ZDV + 3TC)
Dosing: 300 mg BID
Adverse Effects: Bone marrow suppression (macrocytic anemia, neutropenia), Lactic Acidosis
NNRTIs
1) Delavirdine (DLV, Rescriptor) [NOTE: Rarely prescribed]
Dosing: 400 mg TID
Adverse Effects: Rash, Increased transaminases, headaches
2) Efavirenz (EFV, Sustiva)
Dosing: 600 mg QHS
Adverse Effects: Rash, CNS symptoms, Increased transaminases
3) Nevirapine (NVP, Viramune)
Dosing: 200 mg Daily x 14 days and then 200 mg BID thereafter
Adverse Effects: Rash, Stevens-Johnson, Hepatotoxicity (especially in women with a baseline CD4 cell
count above 250/µL)
PIs
1) Amprenavir (APV, Agenerase) [NOTE: No longer manufactured; Fosamprenavir (#3 below), a prodrug,
has taken its place.]
Dosing: 1400 mg BID
Adverse Effects: Rash, GI intolerance, Hyperlipidemia, Transaminase elevation, Hyperglycemia, Fat
maldistribution
2) Atazanavir (ATV, Reyataz)
Dosing: 400 mg Daily (unboosted) or (more commonly) 300 mg (w/ RTV 100mg) Daily
Adverse Effects: Indirect Hyperbilirubinemia, PR prolongation, Hyperglycemia, Fat maldistribution
3) Fosamprenavir (f-APV, Lexiva)
Dosing: 1400 mg BID (unboosted) or 1200 mg (w/ RTV 200 mg) Daily or 600 mg (w/ RTV 100 mg) BID
Adverse Effects: Rash, GI intolerance, Hyperlipidemia, Transaminase elevation, Hyperglycemia, Fat
maldistribution
4) Indinavir (Crixivan)
Dosing: 800 mg TID or 800 mg (w/ RTV 100-200 mg) BID
Adverse Effects: Nephrolithiasis, Indirect Hyperbilirubinemia, GI intolerance, Hyperlipidemia,
Hyperglycemia, Hemolytic Anemia, Thrombocytopenia, Alopecia
5) Lopinavir + Ritonavir (LPV/r, Kaletra)
Dosing: LPV 400 mg + RTV 100 mg BID
Adverse Effects: GI intolerance, Hyperlipidemia, Transaminase elevation, Hyperglycemia, Fat
maldistribution
6) Nelfinavir (NFV, Viracept)
Dosing: 1250 mg BID or 750 mg TID
Adverse Effects: Diarrhea, Hyperlipidemia, Hyperglycemia, Fat maldistribution, Transaminase elevation
7) Ritonavir (RTV, Norvir) [NOTE: Rarely prescribed as PI because of GI intolerance; more commonly
used as booster.]
Dosing: 600 mg Q 12 (when used alone). 100-400 mg / day in 1-2 divided doses (when used as booster
for other PIs)
Adverse Effects: GI intolerance, Parasthesias, Hyperlipidemia, Hepatitis, Hyperglycemia, Fat
maldistribution
8) Saquinavir (SQV, Invirase)
Dosing: 1000 mg (w/ RTV 100 mg) BID
Adverse Effects: GI intolerance, Hyperlipidemia, Transaminase elevation, Hyperglycemia, Fat
maldistribution
9) Saquinavir Soft Gel Capsule (SQV-sgc, Fortovase) [NOTE: No longer manufactured.]
Dosing: 1200 mg TID (unboosted) or 1000 mg (w/ RTV 100 mg) BID
Adverse Effects: GI intolerance, Hyperlipidemia, Transaminase elevation, Hyperglycemia, Fat
maldistribution
Fusion Inhibitors
1) Enfuvirtide (T20, Fuzeon)
Dosing: 90 mg SC BID
Adverse Effects: Local injection site reactions, Increased bacterial pneumonias, Hypersensitivity reaction
General principles on side effects:
NRTIs:
1. Lactic acidosis: d4T/ddI > d4T > ddI > ZDV
2. Peripheral neuropathy usually due to the following in rank order: d4T/ddI > ddI > d4T.
3. Pancreatitis is most commonly due to the following rank order: d4T/ddI > ddI > d4T
PIs:
1. Lipodystrophy syndrome (Hyperlipidemia, Hyperglycemia, Fat maldistribution)
***d4T is also associated with lipoatrophy and lipid abnormalities
2. GI intolerance
3. Increased transaminases
NNRTIs:
1. Increased transaminases
2. Rash
Potential Long Term Treatment Complications of Antiretroviral Therapy:
1. Premature bone loss / Osteopenia
2. Avascular necrosis of the hips
3. Atherosclerotic Disease / Coronary Artery Disease
4. Lactic Acidosis
5. Lipodystrophy Syndrome
IV. Regimen examples:
The guidelines of the US Department of Health and Human Services (DHHS) for initial treatment
regimens are as follows:
1) PI-based regimen:
PI: LPV/r (Lopinavir + Ritonavir, Kaletra) +
NRTI: ZDV (Zidovudine, AZT, Retrovir) +
NRTI: 3TC (Lamivudine) or FTC (Emtricitabine, Emtriva)
2) NNRTI-based regimen:
NNRTI: EFV (Efavirenz, Sustiva) +
NRTI: ZDV (Zidovudine, AZT, Retrovir) or TDF (Tenofovir, Viread) +
NRTI: 3TC (Lamivudine) or FTC (Emtricitabine, Emtriva)
**Remember: Truvada = TDF (Tenofovir, Viread) plus FTC (Emtricitabine, Emtriva)
Combivir = 3TC (Lamivudine) plus ZDV (Zidovudine, AZT, Retrovir)