A Virological Benefit from an Induction/Maintenance Strategy: The Forte Trial

Objective To evaluate whether the addition of a fourth drug for up to 32 weeks to a standard three-drug anti-retroviral combination decreases the risk of virological failure without increasing toxicity in treatment-naive patients. Design Induction/maintenance (IM) therapy [two nucleoside reverse transcriptase inhibitors (NRTIs) + one non-NRTI (NNRTI) + one protease inhibitor for 24–32 weeks until plasma HIV RNA viral load (VL) ≤50 copies/ml then two NRTIs + NNRTI] was compared with standard therapy (ST) (two NRTIs + NNRTI). The primary endpoint was virological failure: VL >50 copies/ml at 32 (and 24) weeks or subsequent rebound to >400 copies/ml. Results 122 (62 IM, 60 ST) participants were randomized and followed for a median of 81 weeks (IQR 64–145). 52% were asymptomatic; median CD4 + T-cell count was 160x10 6 /l (IQR 92-260) and median VL 98,830 copies/ml (IQR 37,500–241,290). In an intent-to-treat analysis, the proportion of participants with virological failure at or after 32 weeks was higher in the ST arm [26 (43%) versus 11 (18%), P=0.002]. The mean decrease in VL at 48 weeks was 0.84 95% confidence interval (CI) (0.15, 1.53) log 10 copies/ml greater in the IM arm ( P=0.02). There were no significant differences between the two arms in the change in CD4 + T-cell count from baseline to 48 weeks, the number of participants with adverse events or the frequency of progression to AIDS/death. Drug resistance at failure was detected less frequently in the IM arm. Conclusions Starting antiretroviral therapy with an IM strategy improved virological outcomes compared with a three-drug regimen, without significantly increasing toxicity.