Efficacy, Tolerability and Virological Consequences of Long-Term Use of Unboosted Atazanavir Plus 2 NRTIs in HIV-Infected Patients

Title:Efficacy, Tolerability and Virological Consequences of Long-Term Use of Unboosted Atazanavir Plus 2 NRTIs in HIV-Infected Patients

Volume: 12 Issue: 5

Author(s): S. Bonora, A. Calcagno, O. Vigano, P. Bigliano, L. Marinaro, E. Colella, G. Orofino, L. Trentini, M.C. Tettoni, A. D'Avolio, S. Mercadante, M. Galli, G. Di Perri and S. Rusconi

Affiliation:

Keywords: Drug resistance, I50L, unboosted atazanavir, pharmacokinetics.

Abstract: Purpose: Switch to unboosted atazanavir (ATV) is an attractive option due to convenience and tolerability in HIV-positive patients. With limited available data we investigated the determinants of long-term efficacy and the consequences of virological failure of unboosted atazanavir-based regimens.

Methods: Retrospective analysis in two Italian large outpatient clinics including demographic, immunovirological, resistance and pharmacokinetic data.

Results: 249 patients receiving atazanavir (400 mg once-daily) plus 2 NRTIs were included; 163 were males (65.5%) and median age was 47 years (42-51.5). Median CD4+ T-cell count was 396/uL (261-583); 146 (58.6%) presented a viral load <50 copies/mL. Over a median follow up of 157 weeks (106-203) 193 patients (77.5%) were still on treatment with 10 (4%) and 2 (0.8%) stopping for virological failure or toxicity, respectively. Ten patients with virological failure presented newly selected resistance associated mutations (RAMs) for NRTIs (2/10) or ATV (4/10, one I50L). Total cholesterol and triglycerides showed significant decreases at 48 [-4 mg/dL and -41 mg/dL] and 96 weeks [-14 mg/dL and -54 mg/dL] as compared to baseline. At multivariate analysis a genotypic sensitivity score ≤1, atazanavir RAMs >1 and suboptimal adherence were independently associated with virological failure; in lamivudine/emtricitabine-treated patients the presence of M184V (without other NRTI RAMs) was not associated with virological failure.

Conclusion: Unboosted-atazanavir containing regimens were efficacious (with uncommon virological failures) and welltolerated (with improvements in lipid profile over time) treatments in HIV-positive patients. Isolated M184V in lamivudine/emtricitabine recipients was not associated with higher failure rates supporting the use of functional ATVbased dual therapies as maintenance strategies.

Cite this article as:

Bonora S., Calcagno A., Vigano O., Bigliano P., Marinaro L., Colella E., Orofino G., Trentini L., Tettoni M.C., D'Avolio A., Mercadante S., Galli M., Perri Di G. and Rusconi S., Efficacy, Tolerability and Virological Consequences of Long-Term Use of Unboosted Atazanavir Plus 2 NRTIs in HIV-Infected Patients, Current HIV Research 2014; 12 (5) . https://dx.doi.org/10.2174/1570162X12666140807151616