Suboptimal Adherence May Have Less Detrimental Effect in Patients Taking Boosted Darunavir (Prezista)

Several studies in the era of highly active antiretroviral therapy (ART) have indicated that near-perfect adherence is important for achieving optimal outcomes. But some drugs are more "forgiving" of suboptimal adherence than others.

Research has shown that treatment failure is more likely to occur when patients do not achieve complete adherence to non-nucleoside reverse transcriptase inhibitors (NNRTIs) compared with ritonavir-boosted protease inhibitors. Now, a study presented at the 15th British HIV Association Meeting (BHIVA 2009) this month in Liverpool suggests there are also differences among drugs in the protease inhibitor class.

Prezista Tablet

Mark Nelson and colleagues presented 96 week results on adherence, efficacy, and adverse events from the Phase III ARTEMIS study (also known as TMC114-C211, sponsored by darunavir producer Tibotec), which compared 800 mg once-daily darunavir (Prezista, formerly designated TMC114) boosted with 100 mg low-dose ritonavir versus 800/200 mg lopinavir/ritonavir (Kaletra), both with a backbone of tenofovir/emtricitabine (Truvada), in treatment-naive HIV patients.

As previously reported, darunavir/ritonavir demonstrated significantly higher virological response rates at week 96 than lopinavir/ritonavir using an intent-to-treat time-to-loss of virological response (ITT TLOVR) analysis (79% vs 71%; P = 0.012). Both treatments were generally well tolerated, though patients in the darunavir/ritonavir arm were less likely to experience grade 2-4 diarrhea or blood lipid abnormalities.

In the present analysis, the investigators showed that good adherence predicted long-term treatment response. Overall, adherence rates were similar -- and generally quite high -- in both treatment arms. Adherence levels varied across regional and racial/ethnic subgroups, and patients who reported adverse side effects had poorer adherence.

But while patients with good (95% or better) adherence had similar response rates in the darunavir/ritonavir and lopinavir/ritonavir arms (82% vs 78%, respectively, with HIV RNA < 50 copies/mL), those with suboptimal adherence fared better with darunavir/ritonavir (76% vs 53% < 50 copies/mL).

The investigators concluded that, "The efficacy of once-daily darunavir/ritonavir in suboptimally adherent patients was minimally compromised compared with adherent patients" and "[s]uboptimal adherence to darunavir/ritonavir had less effect on virological response than suboptimal adherence to lopinavir/ritonavir."

Complete results from the study are provided in the poster PDF.

Chelsea and Westminster Hospital, London, UK; Hôpital Saint-Antoine, Paris, France; Tibotec Inc., Yardley, PA; Tibotec BVBA, Mechelen, Belgium.

4/17/09

Reference
M Nelson, P-M Girard, R DeMasi, and others. Adherence to darunavir/ritonavir and lopinavir/ritonavir in treatment-naive, HIV-infected patients in ARTEMIS: 96-week data. 15th British HIV Association Meeting (BHIVA 2009). Liverpool, UK. April 1-3, 2009. Abstract P115.