Table 309-21.

Antiretroviral Drugs Used in the Treatment of HIV Infection Dose as Dose in Drug Status Indication Monotherapy Combination REVERSE TRANSCRIPTASE INHIBITORS Zidovudine (AZT, Licensed Treatment of HIV Not indicated 200 mg q8h or 300 azidothymidine infection when mg bid , Retrovir, antiretroviral therapy is 3 azido-3 indicated deoxythymidin e) Prevention of Mother: 100 mg 5 maternal-fetal HIV /d until the start transmission of labor, then 2 mg/kg over 1 h IV, followed by 1 mg/kg per h IV until clamping of umbilical cord; Infant: 2 mg/kg q6h PO beginning within 12 h birth, or 1.5 mg/kg q6h IV over 30 min Didanosine Licensed For treatment of HIV Not indicated Requires 2 tablets to (Videx, ddI, infection when achieve adequate dideoxyinosine, antiretroviral buffering of therapy is stomach acid; 2 ,3 warranted should be dideoxyinosine administered on ) an empty stomach 60 kg: 200 mg bid <60 kg: 125 mg bid 200 mg bid 125 mg bid Zalcitabine (ddC, Licensed In combination with Not indicated 0.75 mg tid other antiretroviral HIVID, 2 3 agents for the dideoxycytidin treatment of HIV e) infection Stavudine (d4T, Zerit, 2 3 didehydro-3 dideoxythymidi ne) Licensed Treatment of HIVinfected patients who have received prolonged prior zidovudine therapy Not indicated 60 kg: 40 mg bid <60 kg: 30 mg bid

Supporting Data 19 vs 1 death in original placebocontrolled trial in 281 patients with AIDS or ARC. Decreased progression to AIDS in patients with CD4+ T cell counts <500/L, n = 2051 In pregnant women with CD4+ T cell count 200/L, AZT PO beginning at weeks 14-34 of gestation plus IV drug during labor and delivery plus PO AZT to infant for 6 wk decreased transmission of HIV by 67.5% (from 25.5% to 8.3%), n = 363

Toxicity Anemia, granulocytopenia, myopathy, lactic acidosis, hepatomegaly with steatosis, headache, nausea

Clinically superior to AZT as monotherapy in 913 patients with prior AZT therapy. Clinically superior to AZT and comparable to AZT + ddI and AZT + ddC in 1067 AZT-naive patients with CD4+ T cell counts of 200-500/L

Pancreatitis, peripheral neuropathy, abnormalities on liver function tests

Clinically inferior to AZT monotherapy as initial treatment. Clinically as good as ddI in advanced patients intolerant to AZT. In combination with AZT, was clinically superior to AZT alone in patients with AIDS or CD4+ T cell count <350/L Superior to AZT with respect to changes in CD4+ T cell counts in 359 patients who had received 24 wk of AZT. Following 12 wk of randomization, the CD4+ T cell count had decreased in AZT-treated controls by a mean of 22/L, while in stavudine-treated patients, it had

Peripheral neuropathy, pancreatitis, lactic acidosis, hepatomegaly with steatosis, oral ulcers Peripheral neuropathy, pancreatitis

Lamivudine (Epivir, 2 3 dideoxy-3 thiacytidine, 3TC)

Licensed

In combination with other antiretroviral agents for the treatment of HIV infection

Not indicated

150 mg bid

Abacavir (Ziagen)

Licensed

For treatment of HIV infection in combination with other antiretroviral agents

Not indicated

300 mg bid

Delavirdine (Rescriptor)

Licensed

Nevirapine (Viramune)

Licensed

Efavirenz (Sustiva)

Licensed

For use in combination with appropriate antiretrovirals when treatment is warranted In combination with nucleoside analogues for treatment of progressive HIV infection For treatment of HIV infection in combination with other antiretroviral agents

Not indicated

400 mg tid

increased by a mean of 22/L Superior to AZT alone with respect to changes in CD4 counts in 495 patients who were zidovudine-naive and 477 patients who were zidovudine-experienced. Overall CD4+ T cell counts for the zidovudine group were at baseline by 24 wk, while in the group treated with zidovudine plus lamivudine, they were 10-50 cells/L above baseline. 54% decrease in progression to AIDS/death compared to AZT alone 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 cell increase (~100/L in each group) at 24 weeks Delavirdine + AZT superior to AZT alone with regard to viral load suppression at 52 weeks

Hypersensitivity reaction (can be fatal); fever, rash, nausea, vomiting, malaise or fatigue, and loss of appetite

Skin rash, abnormalities in liver function tests

Not indicated

200 mg/d 14 days then 200 mg bid

Increases in CD4+ T cell count, decrease in HIV RNA when used in combination with nucleosides

Skin rash, abnormalities in liver function tests

Not indicated

600 mg qhs

PROTEASE INHIBITORS Saquinavir Licensed mesylate (Invirase hard gel capsule)

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; however, the discontinuation rate in the indinavir group was unexpectedly high, accounting for most treatment "failures") and CD4 cell increase (~140/L in each group) at 24 weeks Increases in CD4+ T cell counts, reduction in HIV RNA most pronounced in combination therapy with ddC. 50% reduction in first

Rash, dysphoria, elevated liver function tests

In combination with other antiretroviral agents when therapy is

Not indicated

600 mg q8h

Diarrhea, nausea, headaches, hyperglycemia, fat redistribution, lipid

warranted (Fortovase soft gel capsule) Licensed For use in combination with other antiretroviral agents when treatment is warranted In combination with nucleoside analogues for treatment of HIV infection when treatment is warranted For treatment of HIV infection when antiretroviral treatment is warranted Not indicated 1200 mg tid

AIDS-defining event or death in combination with ddC compared to either agent alone Reduction in the mortality rate and AIDS-defining events for patients who received hard-gel formulation in combination with ddC Reduction in the cumulative incidence of clinical progression or death from 34 to 17% in patients with CD4+ T cell count <100/L treated for a median of 6 months Increase in CD4+ T cell count by 100/L and 2-log decrease in HIV RNA levels when given in combination with zidovudine and lamivudine. Decrease of 50% in risk of progression to AIDS or death when given with zidovudine and lamivudine compared with zidovudine and lamivudine alone 2.0-log decline in HIV RNA when given in combination with stavudine

abnormalities Diarrhea, nausea, abdominal pain, headaches, hyperglycemia, fat redistribution, lipid abnormalities Nausea, abdominal pain, hyperglycemia, fat redistribution, lipid abnormalities, may alter levels of many other drugs, including saquinavir Nephrolithiasis, indirect hyperbilirubinemia, hyperglycemia, fat redistribution, lipid abnormalities

Ritonavir (Norvir)

Licensed

Not indicated

600 mg bid

Indinavir sulfate (Crixivan)

Licensed

Not indicated

800 mg q8h

Nelfinavir mesylate (Viracept) Amprenavir (Agenerase)

Licensed

Licensed

For treatment of HIV infection when antiretroviral therapy is warranted In combination with other antiretroviral agents for treatment of HIV infection

Not indicated

750 mg tid or 1250 mg bid

Diarrhea, loose stools, hyperglycemia, fat redistribution, lipid abnormalities Nausea, vomiting, diarrhea, rash, oral paresthesias, elevated liver function tests, hyperglycemia, fat redistribution, lipid abnormalities

Not indicated

1200 mg bid

Lopinavir/ritonav ir (Kaletra)

Licensed

For treatment of HIV infection

Not indicated

400 mg/100 mg bid

In treatment-naive patients, amprenavir + AZT + 3TC superior to AZT + 3TC with regard to viral load suppression (53% vs 11% with <400 HIV RNA copies/mL plasma at 24 weeks). CD4+ T cell responses similar between treatment groups. In treatment-experienced patients, amprenavir + NRTIs similar to indinavir + NRTIs with regard to viral load suppression (43% vs 53% with <400 HIV RNA copies/mL plasma at 24 weeks). CD4+ T cell responses superior in the indinavir + NRTIs group In treatment of naive patients, lopinavir/ritonavir + d4T + 3TC superior to nelfinavir + d4T + 3TC with regard to viral load suppression

Diarrhea, hyperglycemia, fat redistribution, lipid abnormalities

(79% vs 64% with <400 HIV RNA copies/mL at 40 weeks). CD4+ T cell increases similar in both groups. NOTE: ARC, AIDS-related complex; NRTIs, nonnucleoside reverse transcriptase inhibitors.