Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial. (Original Contribution)

Adding a second protease inhibitor to highly active antiretroviral therapy (HAART) may benefit some HIV patients, according to a study of 481 patients. About one-third of the patients achieved viral blood levels below 200 copies/mL.
Context: Management of antiretroviral treatment failure in patients receiving protease inhibitor (PI)-containing regimens is a therapeutic challenge. Objective: To assess whether adding a second PI improves antiviral efficacy of a 4-drug combination in patients with virologic failure while taking a PI-containing regimen. Design: Multicenter, randomized, 4-arm trial, double-blind and placebo-controlled for second PI, conducted between October 1998 and April 2000, for which there was a 24-week primary analysis with extension to 48 weeks. Setting: Thirty-one participating AIDS (acquired immunodeficiency syndrome) Clinical Trials Units in the United States. Participants: A total of 481 human immunodeficiency virus (HIV)-infected persons with prior exposure to a maximum of 3 PIs and viral load above 1000 copies/mL. Intervention: Selectively randomized assignment (per prior PI exposure) to saquinavir (n = 116); indinavir (n=69); nelfinavir (n = 139); or placebo twice per day (n = 157); in combination with amprenavir, abacavir, efavirenz, and adefovir dipivoxil. Main Outcome Measures: Primary efficacy analysis involved the proportion with viral load below 200 copies/mL at 24 weeks. Other measures were changes in viral load and CD4 cell count from baseline, adverse events, and HIV drug susceptibility. Results: Of 481 patients, 148 (31%) had a viral load below 200 copies/mL at week 24. The proportions of patients with a viral load below 200 copies/mL in the saquinavir, indinavir, nelfinavir, and placebo arms were 34% (40/116), 36% (25/69), 34% (47/139), and 23% (36/157), respectively. The proportion in the combined dual-PI arms was higher than in the amprenavir-plus-placebo arm (35% [112/324] vs 23% [36/157], respectively; P=.002). Overall, a higher proportion of nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients had a viral load below 200 copies/mL compared with NNRTI-experienced patients (43% [115/270) vs 16% [33/ 211], respectively; P Conclusions: In this study of antiretroviral-experienced patients with advanced immunodeficiency, viral load suppression to below 200 copies/mL was achieved in 31 % of patients with regimens containing 4 or 5 new drugs. Use of 2 PIs, being naive to N NRTIs, and baseline hypersusceptibility to efavirenz were associated with a favorable outcome.