A New Paradigm for Treating Drug-Resistant HIV - Infectious ...

http://infectious-diseases.jwatch.org/cgi/content/full/2007/418/1

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A New Paradigm for Treating Drug-Resistant HIV

Results from the POWER 1 and 2 studies at 48 weeks show that darunavir-ritonavir is efficacious against HIV resistant to older protease inhibitors. 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). Comment: DRV/r received FDA approval in 2006, based on results from the POWER studies. The 48-week results, presented previously at meetings, have now been published. The main importance of the POWER studies is that they have moved the goalposts for new antiretroviral agents. Now that we are able to treat patients with several new agents simultaneously (e.g., novel protease inhibitors, enfuvirtide, and drugs in development such as integrase inhibitors and CCR5 antagonists), we may be able to achieve virologic suppression in most patients infected with drug-resistant HIV. Rajesh T. Gandhi, MD Published in Journal Watch Infectious Diseases April 18, 2007

Citation(s):
Clotet B et al. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: A pooled subgroup analysis of data from two randomised trials. Lancet 2007 Apr 7; 369:1169-78. Medline abstract (Link to: /cgi/external_ref?access_num=17416261&link_type=MED) (Free)

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