Antiretroviral Drugs Used in the Treatment of HIV Infection
| Drug | Status | Indication | Dose in Combination | Supporting Data | Toxicity |
|---|---|---|---|---|---|
| Nucleoside or Nucleotide Reverse Transcriptase Inhibitors | |||||
| Zidovudine (AZT, azidothymidine, Retrovir, 3'azido-3'-deoxythymidine) | Licensed | Treatment of HIV infection in combination with other antiretroviral agents | 200 mg q8h or 300 mg bid | 19 vs 1 death in original placebo-controlled trial in 281 patients with AIDS or ARC | Anemia, granulocytopenia, myopathy, lactic acidosis, hepatomegaly with steatosis, headache, nausea, nail pigmentation, lipid abnormalities, lipoatrophy, hyperglycemia |
| Prevention of maternal-fetal HIV transmission | In pregnant women with CD4+ T cell count ≥200/µL, AZT PO beginning at weeks 14-34 of gestation plus IV drug during labor and delivery plus PO AZT to infant for 6 weeks decreased transmission of HIV by 67.5% (from 25.5% to 8.3%), n = 363 | ||||
| Lamivudine (Epivir, 2'3'-dideoxy-3'-thiacytidine, 3TC) | Licensed | In combination with other antiretroviral agents for the treatment of HIV infection | 150 mg bid 300 mg qd | In combination with AZT superior to AZT alone with respect to changes in CD4+ T cell counts in 495 patients who were zidovudine-naïve and 477 patients who were zidovudine-experienced; overall CD4+ T cell counts for the zidovudine group were at baseline by 24 weeks, while in the group treated with zidovudine plus lamivudine, they were 10-50 cells/µL above baseline; 54% decrease in progression to AIDS/death compared with AZT alone | Flare of hepatitis in HBV-co-infected patients who discontinue drug |
| Emtricitabine (FTC, Emtriva) | Licensed | In combination with other antiretroviral agents for the treatment of HIV infection | 200 mg qd | Comparable to stavudine in combination with didanosine and efavirenz in 571 treatment-naïve patients; similar to 3TC in combination with AZT or stavudine + NNRTI or PI in 440 patients doing well for ≥12 weeks on a 3TC regimen | Hepatotoxicity in HBV-co-infected patients who discontinue drug, skin discoloration |
| Abacavir (Ziagen) | Licensed | For treatment of HIV infection in combination with other antiretroviral agents | 300 mg bid | Abacavir + AZT + 3TC equivalent to indinavir + AZT + 3TC with regard to viral load suppression (~60% in each group with <400 HIV RNA copies/mL plasma) and CD4+ T cell increase (~100/µL in each group) at 24 weeks | Hypersensitivity reaction In HLA-B5701+ individuals (can be fatal); fever, rash, nausea, vomiting, malaise or fatigue, and loss of appetite |
| Tenofovir (Viread) | Licensed | For use in combination with other antiretroviral agents when treatment is indicated | 300 mg qd | Reduction of ~0.6 log in HIV-1 RNA levels when added to background regimen in treatment-experienced patients | Renal, osteomalacia, flare of hepatitis in HBV-co-infected patients who discontinue drug |
| Non-Nucleoside Reverse Transcriptase Inhibitors | |||||
| Nevirapine (Viramune) | Licensed | In combination with other antiretroviral agents for treatment of progressive HIV infection | 200 mg/d × 14 days then 200 mg bid or 400 mg extended release qd | Increase in CD4+ T cell count, decrease in HIV RNA when used in combination with nucleosides | Skin rash, hepatotoxicity |
| Efavirenz (Sustiva) | Licensed | For treatment of HIV infection in combination with other antiretroviral agents | 600 mg qhs | Efavirenz + AZT + 3TC comparable to indinavir + AZT + 3TC with regard to viral load suppression (a higher percentage of the efavirenz group achieved viral load <50 copies/mL, but the discontinuation rate in the indinavir group was unexpectedly high, accounting for most treatment “failures”); CD4 cell increase (~140/µL in each group) at 24 weeks | Rash, dysphoria, elevated liver function tests, drowsiness, abnormal dreams, depression, lipid abnormalities, potentially teratogenic |
| Etravirine (Intelence) | Licensed | In combination with other antiretroviral agents in treatment-experienced patients whose HIV is resistant to nonnucleoside reverse transcriptase inhibitors and other antiretroviral medications | 200 mg bid | Higher rates of HIV RNA suppression to <50 copies/mL (56% vs 39%); greater increases in CD4+ T cell count (89 vs 64 cells) compared to placebo when given in combination with an optimized background regimen | Rash, nausea, hypersensitivity reactions |
| Rilpivirine (Edurant) | Licensed | In combination with other drugs in previously untreated patients when treatment is indicated. | 25 mg qd | Noninferior to efavirenz with respect to suppression at week 48 in 1368 treatment-naive individuals except in patients with pretherapy HIV RNA levels >100,000 where it was inferior | Nausea, dizziness, somnolence, vertigo, less CNS toxicity and rash than Efavirenz |
| Protease Inhibitors | |||||
Ritonavir (Norvir) | Licensed | In combination with other antiretroviral agents for treatment of HIV infection when treatment is warranted | 600 mg bid (also used in lower doses as pharmacokinetic booster) | Reduction in the cumulative incidence of clinical progression or death from 34% to 17% in patients with CD4+ T cell count <100/µL treated for a median of 6 months | Nausea, abdominal pain, hyperglycemia, fat redistribution, lipid abnormalities, may alter levels of many other drugs, paresthesias, hepatitis |
Atazanavir (Reyataz) | Licensed | For treatment of HIV infection in combination with other antiretroviral agents | 400 mg qd or300 mg qd + ritonavir100 mg qd when given with efavirenz | Comparable to efavirenz when given in combination with AZT + 3TC in a study of 810 treatment-naïve patients; comparable to nelfinavir when given in combination with stavudine + 3TC in a study of 467 treatment-naïve patients | Hyperbilirubinemia, PR prolongation, nausea, vomiting, hyperglycemia, fat maldistribution, rash transaminase elevations, renal stones |
| Darunavir (Prezista) | Licensed | In combination with 100 mg ritonavir for combination therapy in treatment-experienced adults | 600 mg + 100 mg ritonavir twice daily with food | At 24 weeks, patients with prior extensive exposure to antiretrovirals treated with a new combination including darunavir showed a -1.89-log change in HIV RNA levels and a 92-cell increase in CD4+ T cells compared with -0.48 log and 17 cells in the control arm | Diarrhea, nausea, headache, skin rash, hepatotoxicity, hyperlipidemia, hyperglycemia |
| Entry Inhibitors | |||||
| Enfuvirtide (Fuzeon) | Licensed | In combination with other agents in treatment-experienced patients with evidence of HIV-1 replication despite ongoing anti-retroviral therapy | 90 mg SC bid | In treatment of experienced patients, superior to placebo when added to new optimized background (37% vs 16% with <400 HIV RNA copies/mL at 24 weeks; + 71 vs + 35 CD4+ T cells at 24 weeks) | Local injection reactions, hypersensitivity reactions, increased rate of bacterial pneumonia |
| Maraviroc (Selzentry) | Licensed | In combination with other antiretroviral agents in adults infected with only CCR5-tropic HIV-1 | 150-600 mg bid depending on concomitant medications (see text) | At 24 weeks, among 635 patients with CCR5-tropic virus and HIV-1 RNA >5000 copies/mL despite at least 6 months of prior therapy with at least 1 agent from 3 of the 4 antiretroviral drug classes, 61% of patients randomized to maraviroc achieved HIV RNA levels <400 copies/mL compared with 28% of patients randomized to placebo | Hepatotoxicity, nasopharyngitis, fever, cough, rash, abdominal pain, dizziness, musculoskeletal symptoms |
| Integrase Inhibitor | |||||
| Raltegravir (Isentress) | Licensed | In combination with other antiretroviral agents | 400 mg bid | At 24 weeks, among 436 patients with 3-class drug resistance, 76% of patients randomized to receive raltegravir achieved HIV RNA levels <400 copies/mL compared with 41% of patients randomized to receive placebo | Nausea, headache, diarrhea, CPK elevation, muscle weakness, rhabdomyolysis |
Elvitegravir | Licensed | In combination with other antiretroviral agents | 1 tablet daily | Noninferior to raltegravir or atazanavir/ritonavir in treatment-experienced patients. | Diarrhea, nausea, upper respiratory infections, headache |
Dolutegravir (Tivicay) | Licensed | In combination with other antiretroviral agents | 50 mg daily for treatment-naïve patients; 50 mg twice daily for treatment-experienced patients or those also receiving efavirenz or rifampin | Noninferior to raltegravir, superior to efavirenz or darunavir/ritonavir | Insomnia, headache, hypersensitivity reactions, hepatotoxicity |
Abbreviations: ARC, AIDS-related complex; NRTIs, nonnucleoside reverse transcriptase inhibitors.