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Background:  This study was designed to determine the effect of switching treatment-experienced patients with virologic failure to a salvage regimen with or without a 12- week structured treatment interruption (STI). The primary endpoint is the percentage of patients with a viral load of < 50 copies/mL and who maintained this degree of suppression for at least 3 months while still on the initial salvage regimen.

Methods:  A randomized, open-label multicenter trial, in patients with virologic failure (viral load > 1000 copies/mL) on a HAART regimen, requiring a switch in ARV therapy and who had at least 2 new ARV available based on history that could be included in the salvage regimen of 3 to 5 agents. Patients were stratified as to whether they had received prior therapy with an non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) or both. The salvage regimen, determined prior to randomization, was guided by a baseline genotype and virtual phenotype. Patients were followed for 60 weeks after randomization. The trial was terminated prematurely by the SERC after enrollment of 147 of 196 expected patients because of slow recruitment.

Results:  The current analysis includes 134 patients with at least 1 post-baseline viral load and randomized before January 1, 2004 (67 in the immediate switching [IS] and 67 in the STI arm). Patients were 87% male, had median baseline CD4 count 343/mm³ and viral load of 3.9 log; 71 had received a prior PI or NNRTI, and 63 had received both. Baseline values were similar for the two groups. Success as defined by the primary endpoint was achieved by 69% patients in the IS and 55% patients in the STI arms (p = 0.11; 95% CI= –4% to 31% IS). During the 60 weeks, there were 2 non-HIV-related deaths (1 IS, 1 STI), 4 AIDS-defining events in the STI arm (Pneumocystis pneumonia week 7, lymphoma week 57, 2 episodes of esphageal Candida in 1 patient weeks 28 and 43) and 7 HIV-associated infections (5 episodes of zoster in 3 STI and 2 IS and 2 episodes of oral thrush in STI).

Virologic endpoints were:

Median differences from baseline in CD4 count and log (viral load) were:

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Conclusions:  In this randomized controlled clinical trial, a 12-week STI prior to the initiation of a salvage HAART therapy did not improve outcomes. There was no difference in the percentage of patients who could sustain a viral load of < 50/mL for 3 months, and there was a statistically lower CD4 cell count rise but similar viral load reduction at 60 weeks.

Keywords: structured treatment interruption; salvage therapy; antiretroviral therapy