A New Paradigm for Treating Drug-Resistant HIV

A growing number of HIV-infected patients have strains that are resistant to current classes of antiretroviral agents. In the similarly designed, multinational POWER 1 and 2 trials, researchers examined the safety and efficacy of darunavir coadministered with low-dose ritonavir (DRV/r) in patients who had extensive treatment experience with older protease inhibitors (PIs) and with other classes of antiretroviral medications. Based on 24-week results, the 600/100-mg twice-daily dose of DRV/r was selected for further testing.

Now, in a manufacturer-supported pooled subgroup analysis, researchers have compared 48-week results between the 110 patients randomized to receive DRV/r at 600/100 mg twice daily and the 120 randomized to receive a control PI. All participants also received an individually optimized background regimen. Nearly two thirds of the patients in each group were infected with HIV that was resistant to all PIs then commercially available. (Tipranavir was not available; most isolates were susceptible to this drug.)

At 48 weeks, 61% of the DRV/r group and 15% of the control group had viral load (VL) declines >1 log₁₀ copies/mL. The proportion of patients with VLs <50 copies/mL was also greater in the DRV/r group than among controls (45% vs. 10%). Among enfuvirtide-naive patients who received both DRV/r and enfuvirtide, 58% achieved an undetectable VL. The DRV/r group had a greater increase in CD4-cell count than did the control group (mean increase, 102 vs. 19 cells/mm³). Incidence rates of common adverse events (e.g., diarrhea, nausea, and increased aminotransferase levels) were either similar between groups or lower in the DRV/r group. Incidence of herpes simplex infection was higher in the DRV/r group than in the control group; many of the cases occurred ≤12 weeks after treatment initiation (concomitant with immune reconstitution).