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Although most persons initiating antiretroviral therapy (ART) in the U.S. start with the fixed-dose combination of tenofovir, FTC, and efavirenz, alternatives are needed for patients who cannot tolerate these agents, do not prefer them, or have acquired NNRTI resistance. Under such circumstances, most providers prefer PI-based regimens. The most recently approved PI, darunavir, is not yet indicated for use in treatment-naive individuals, but 48-week results from the ARTEMIS study — presented last fall at ICAAC (AIDS Clin Care Oct 5 2007) and now published in AIDS — are promising.
The ARTEMIS study is an ongoing, industry-sponsored, multisite trial in which 689 treatment-naive adults were randomized to receive either ritonavir-boosted darunavir (800 mg, plus 100 mg of ritonavir, once daily) or lopinavir/ritonavir (800/200 mg once daily or 400/100 mg twice daily). All patients also received fixed-dose tenofovir/FTC.
By week 48, 84% of the ritonavir-boosted darunavir group and 78% of the lopinavir/r group had achieved viral loads <50 copies/mL (P for noninferiority, <0.001). In a stratified analysis, ritonavir-boosted darunavir was superior to lopinavir/r only among those with baseline viral loads ≥100,000 copies/mL (79% vs. 67%; P<0.05). Grade 2–4 gastrointestinal side effects (including diarrhea) were more common with lopinavir/r than with ritonavir-boosted darunavir, as were adverse events leading to permanent drug discontinuation (7% vs. 3%; P<0.05).
Ortiz R et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48. AIDS 2008 Jul 31; 22:1389.
Comment
Like most new antiretrovirals, darunavir was initially approved for use in treatment-experienced HIV-infected patients whose viruses are resistant to several other drugs. Efficacy in that group inevitably leads to speculation regarding a drug’s role in other patient populations, including treatment-naive individuals. In this study, darunavir was compared with lopinavir/r, the de facto standard for PI-based antiretroviral combinations. The results suggest that darunavir given once daily in a dose of 800 mg with 100 mg of ritonavir may be an excellent option for patients in whom an initial PI-based regimen seems preferable. Longer-term data on adverse events — and on resistance mutations that emerge when virologic failure occurs — will help to determine darunavir’s role in early-treatment situations. Darunavir will be a welcome addition to our current choices for initiating ART and, indeed, was added to the list of preferred PI-based initial therapies in the latest International AIDS Society–USA guidelines.