Darunavir Resistance in HIV Infecting Protease Inhibitor-Experienced Mexican Patients

Abstract

Background: Darunavir (DRV) is a useful antiretroviral treatment in the salvage therapy of multiclass-resistant HIV-infected patients. This study’s aim was to determine the frequency and risk factors for DRV resistance-associated mutations (DRV-RAM) among DRV-naive Mexican patients with virologic failure after extensive antiretroviral treatment and exposure to at least one protease inhibitor (PI). Methods: HIV-infected patients with a history of at least 2 failed regimes were included and their clinical histories and genotype resistance tests were analyzed. Major PI resistance-associated mutations (PI-RAM), DRV-RAM and resistance to DRV were defined according to the IAS-USA criteria. Previous exposure to PI was compared between patients with DRV-resistant HIV and DRV-susceptible HIV-infected controls. Results: The median number of major PI-RAM was 2 (IQR = 0 - 3). In 54.7% (95% CI = 50.0% - 59.4%) of 631 subjects, no DRV-RAM were found on viral genotyping and 6.7% (95% CI = 4.8% - 8.6%) had 3 or more DRV-RAM. The two most frequently found DRV-RAM were in codons I84V (in 22.7% of cases) and L 33F (in 20% of cases) in the viral protease gene. The number of major PI-RAM (as a surrogate marker of duration and number of PI used) and previous exposure to (fos) amprenavir or tipranavir were independently associated with DRV-resistant HIV infection. Conclusions: In this Mexican population, despite a high prior PI exposure, HIV-DRV resistance rate is relatively low and successful viral control with DRV-containing combined salvage therapy is expected in most patients.