Efficacy and safety of abacavir plus lamivudine versus didanosine plus stavudine when combined with a protease inhibitor, a nonnucleoside reverse transcriptase inhibitor, or both in HIV-1 positive antiretroviral-naive persons.

PURPOSE: The combination of abacavir + lamivudine (ABC+3TC) versus didanosine + stavudine (ddI+d4T), each combined with other classes of antiretrovirals (ARVs) in ARV-naive patients, was compared for the combined endpoint of time to plasma HIV RNA >50 copies/mL (at or after the 8-month visit) or death (primary endpoint) in a nested substudy of an ongoing multicenter randomized trial. METHOD: The substudy enrolled 182 patients; mean HIV RNA and CD4+ cell counts at baseline were 5.1 log10 copies/mL and 212 cells/mm3, respectively. RESULTS: After a median follow-up of 28 months, rates of primary endpoint were 57.2 and 67.8 per 100 person-years for the ABC+3TC and ddI+d4T groups (hazard ratio [HR]=0.81, 95% confidence interval [CI] 0.58-1.14, p=.23). CONCLUSION: There was a trend for treatments containing ABC+3TC to be better than treatments containing ddI+d4T with respect to HIV RNA decreases, CD4+ cell count increases, and tolerability.

Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection.

BACKGROUND: The optimal antiretroviral treatment for patients who have human immunodeficiency virus (HIV) viremia despite treatment with nucleoside reverse-transcriptase inhibitors (nucleoside analogues) remains uncertain. We studied treatment with regimens that combined two nucleoside analogues, at least one of which was new, with the protease inhibitor nelfinavir, the nonnucleoside reverse-transcriptase inhibitor efavirenz, or both. METHODS: The study included 195 patients who had been treated with nucleoside analogues only, and had a plasma HIV type 1 (HIV-1) RNA level of at least 500 copies per milliliter. Patients were randomly assigned to receive, in addition to two nucleoside analogues, nelfinavir, efavirenz, or nelfinavir plus efavirenz. The primary end point was a plasma HIV-1 RNA level of less than 500 copies per milliliter at week 16. A secondary end point was the composite of the HIV-1 RNA levels measured at weeks 40 and 48. RESULTS: At week 16 and at weeks 40 and 48, the proportions of patients in whom a plasma HIV-1 RNA level of less than 500 copies per milliliter was achieved were, respectively, 81 percent and 74 percent in the nelfinavir-plus-efavirenz group, 69 percent and 60 percent in the efavirenz group, and 64 percent and 35 percent in the nelfinavir group. Quadruple therapy resulted in a higher rate of viral suppression in both the short term (P=0.03) and the long term (P=0.001) than did triple therapy with nelfinavir. Triple therapy with efavirenz conferred a higher rate of long-term suppression than triple therapy with nelfinavir (P=0.004). Quadruple therapy also achieved a higher rate of virologic suppression than triple therapy with efavirenz (P=0.008). CONCLUSIONS: In HIV-infected patients previously treated with nucleoside analogues, treatment with nelfinavir plus efavirenz and at least one new nucleoside analogue achieves a higher rate of viral suppression than do regimens with nucleoside analogues and nelfinavir or efavirenz alone.

In vivo additive antiretroviral effect of combined zidovudine and foscarnet therapy for human immunodeficiency virus infection (ACTG Protocol 053).

Zidovudine and foscarnet each have antiretroviral activity against human immunodeficiency virus (HIV) and, when combined in vitro, inhibit HIV replication in an additive or synergistic fashion. To determine if an in vivo additive or synergistic antiretroviral effect might result from combined therapy, six symptomatic HIV-infected patients were studied who had persistently quantifiable serum HIV p24 antigen despite 9-27 weeks of full-dose oral zidovudine therapy (1200 mg/day). These patients were given intravenous foscarnet (30 mg/kg every 8h) for 2 weeks with continued oral zidovudine for 14 days, followed by zidovudine alone for 6 months. Serum p24 antigen concentrations decreased in all six patients during the period of combined therapy by a mean 53% (P = .005). Subsequently, serum p24 antigen levels rose to the baseline value in four patients after 4-14 weeks. As predicted from in vitro studies, combined treatment with zidovudine and foscarnet resulted in an additive in vivo effect, but the effect was transient.