Efficacy and safety of a switch to unboosted atazanavir in combination with nucleoside analogues in HIV-1-infected patients with virological suppression under antiretroviral therapy

Abstract

Background: Limited data are available on the use of unboosted atazanavir in combination with nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-experienced HIV-infected patients. Methods: We conducted a multicentre, retrospective study among patients with plasma HIV-1 RNA levels ,50 copies/mL under antiretroviral therapy who switched to unboosted atazanavir+ NRTIs between January 2002 and December 2008. Virological failure during follow-up was defined as a confirmed plasma HIV-1 RNA level .50 copies/mL. Baseline risk factors for virological failure were identified using Cox proportional hazards models. Results: A total of 886 patients were analysed. At baseline, median age was 44 years, 71.5% were males and median CD4 cell count was 490 cells/mm 3. NRTIs used in combination with atazanavir were tenofovir, abacavir and emtricitabine/lamivudine in 36.9%, 44.1% and 94.4% of patients, respectively. Median follow-up was 21 months. The 3 year probability of virological failure was 20.1%. Only a history of virological failure under NRTIs [hazard ratio (HR) 1.63, P ¼0.049] and under protease inhibitors (HR 2.04, P ¼ 0.006) were significantly associated with the risk of virological failure. Among the 431 patients without a prior history of virological failure, the 3 year probability of virological failure was 11.3%, and only hepatitis C virus co-infection (HR 2.25, P ¼ 0.026) and abacavir use (HR 0.43, P ¼ 0.04) were associated with the risk of virological failure. Safety of the switch was satisfactory, with improvement of the lipid profile. Conclusions: In patients with virological suppression and no prior history of virological failure, a switch to unboosted atazanavir in combination with NRTIs is associated with a low probability of virological failure and a good safety profile.

Pharmacologic Boosting of Atazanavir in Maintenance HIV-1 Therapy: The COREYA Propensity-Score Adjusted Study

“…The results show that the failure rate at 1, 2 and 3 years using the 200 cp/mL threshold is remarkably low in patients with ATV 0 (0, 4 and 4% respectively) and similar to published figures [3], [4], [11]. In one study, using a VF threshold of <400 cp/mL, the failure rate was <2%, <3% and <5% at 1, 2 and 3 years, respectively [11]. In this group, the only risk factor for failure was co-infection with hepatitis C, and the authors suggested a link between substance abuse and poor compliance [11].…”

“…With this background, not one of the randomized studies demonstrating the non-inferiority of a maintenance strategy with ATV 0 -based triple therapy was conducted in patients receiving TDF [3], [4], [9]. Recently, two cohort studies have demonstrated the durability and safety of maintenance with ATV 0 -based triple therapy co-administered with TDF, but none included direct comparison with a RTV-boosted ATV regimen (ATV/r) [10], [11].…”

Voriconazole and Atazanavir: A CYP2C19-Dependent Manageable Drug–Drug Interaction

“…ATV and RTV AUC and C min were moderately reduced by VOR while C max was not affected, suggesting a possible effect on ATV clearance; one subject showed a low C min (30 ng/ml, below the efficacy cutoff of 150 ng/ml) that was unchanged by the coadministration of VOR. It is noteworthy that such effect of VOR on ATV plasma exposure had a similar magnitude of the one reported for tenofovir, known not to affect the efficacy of ATV, even when used unboosted in patients not harboring virus with protease inhibitorassociated resistance mutations [9,10]. In patient 3, receiving ATV/RAL dual therapy, while unboosted ATV pharmacokinetic profile was substantially unchanged, RAL exposure seemed to be increased by VOR administration (AUC 2.5-fold higher), even if a plausible mechanism of interaction is currently unknown.…”

Pharmacokinetic-Pharmacodynamic Modeling of Unboosted Atazanavir in a Cohort of Stable HIV-Infected Patients

“…Although unboosted atazanavir is not approved by the European Medicines Agency, large-cohort studies have indicated that a significant proportion of patients do receive unboosted ATV in Europe (8)(9)(10), notably as a simplification strategy in treatmentexperienced HIV-infected patients. Those cohort studies have confirmed that, in patients with stable virological suppression and no history of virological failure, the switch to unboosted atazanavir has a good efficacy and safety profile.…”