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 L33F (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.
Highlights
IntroductionRandomized clinical trials have shown that ritonavirboosted darunavir (DRV/r) as a component of salvage regimens (and at least one other fully active drug), leads to significantly higher rates of lasting virological control when compared with conventional protease inhibitors (PI), among patients infected with multidrug-resistant HIV and an extensive treatment history [1,2,3,4,5,6].Eleven specific darunavir resistance-associated mutations (DRV-RAM) in the viral protease gene have been linked to decrease in vitro HIV susceptibility as well as sub-optimal clinical responses to darunavir [7]
Randomized clinical trials have shown that ritonavirboosted darunavir (DRV/r) as a component of salvage regimens, leads to significantly higher rates of lasting virological control when compared with conventional protease inhibitors (PI), among patients infected with multidrug-resistant HIV and an extensive treatment history [1,2,3,4,5,6]
The frequency of darunavir resistance was significantly higher in our study population when compared with a rate of 4.1% reported in a population of PItreated patients in 16 clinics of the Kaiser-Permanente Medical Care Program in Northern California [10], despite an equal median number of PIs administered in both surveys
Summary
Randomized clinical trials have shown that ritonavirboosted darunavir (DRV/r) as a component of salvage regimens (and at least one other fully active drug), leads to significantly higher rates of lasting virological control when compared with conventional protease inhibitors (PI), among patients infected with multidrug-resistant HIV and an extensive treatment history [1,2,3,4,5,6].Eleven specific darunavir resistance-associated mutations (DRV-RAM) in the viral protease gene have been linked to decrease in vitro HIV susceptibility as well as sub-optimal clinical responses to darunavir [7]. A low percentage (ranging between 4.1% and 6.7%) of individuals with 3 or more DRV-RAM, has consistently been found in these surveys These studies have shown an association between the number of prior PI used, the total number of PI resistance mutations, previous treatment with (fos) amprenavir, and WJA. This study’s aim was to determine the frequency and risk factors for DRV resistance-associated mutations (DRV-RAM) among DRV-naïve Mexican patients with virologic failure after extensive antiretroviral treatment and exposure to at least one protease inhibitor (PI). 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
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