Factors predictive of successful darunavir/ritonavir-based therapy in highly antiretroviral-experienced HIV-1-infected patients (the DARWEST study).

BACKGROUND: Darunavir (DRV) is the latest protease inhibitor (PI) to be approved for antiretroviral-naive and -experienced HIV-infected patients.
OBJECTIVES: We examined virologic and immunologic outcomes of highly antiretroviral-experienced patients with triple-class drug resistance receiving DRV/r-based regimens, and attempted to identify factors predictive of virologic success. STUDY
DESIGN: We studied patients beginning a ritonavir-boosted DRV (DRV/r 600/100mg twice daily)-containing regimen. Virologic success was defined as plasma viral load (pVL)<50copies/ml at week 36.
RESULTS: We studied 62 patients with very severe immunodeficiency (CDC stage C in 69% of cases; median CD4 cell nadir 12/mm(3)). They had previously received a median of four PI and had extensive PI resistance, with a median of three major PI and two DRV resistance mutations. The baseline median pVL and CD4 cell count values were 4.6log(10) and 150/mm(3). At week 36, pVL had fallen by 2.6log(10) and the CD4 cell count had risen by 123cells/mm(3). The virologic success rate was 55% overall, and was improved by concomitant first use of enfuvirtide (67%), raltegravir (69%) or etravirine (75%). Virologic success was independently associated with fewer major PI mutations, previous tipranavir exposure, and concomitant first use of enfuvirtide or raltegravir.
CONCLUSIONS: In these highly antiretroviral-experienced patients with triple-class drug resistance, virologic success of DRV-containing regimens was mainly associated with the use of new drug classes and/or fully active drugs. Interestingly, previous tipranavir failure did not undermine the efficacy of DRV, confirming the low level of cross-resistance and, probably, distinct resistance profiles between DRV and tipranavir.