Treatment of advanced HIV disease in antiretroviral-naïve HIV-1-infected patients receiving once-daily atazanavir/ritonavir or twice-daily lopinavir/ritonavir, each in combination with tenofovir disoproxil fumarate and emtricitabine

Abstract

Current guidelines for HIV therapy recommend initiating treatment at a CD4 cell count of 500 cells/mm³. However, a large proportion of patients with HIV infection begin antiretroviral treatment at a more advanced stage. In the CASTLE study, patients with the most advanced HIV disease (CD4 cell count <50 cells/mm³) showed that 78% (45/58) vs. 58% (28/48) of the patients achieved HIV RNA <50 copies/mL in the intent-to-treat analysis at week 96 for atazanavir/ritonavir and lopinavir/ritonavir, respectively. This current sub-analysis of the CASTLE study describes demographics, virologic failure, discontinuations, safety, tolerability, immunologic response, and clinical outcomes for the following baseline strata: CD4 cell count (cells/mm³) <50, 50 to <100, 100 to <200, and ≥200 and HIV RNA (copies/mL) <100,000, 100,000 to <500,000, and ≥500,000. In the lowest CD4 cell count stratum (<50 cells/mm³), the proportion of discontinuations was 2-fold greater for the lopinavir/ritonavir arm (33%) than for the atazanavir/ritonavir arm (16%) with a similar rate of virologic failure between the two groups. Also in this CD4 cell count stratum, grades 2–4 treatment-related adverse events occurred in 25% in the atazanavir/ritonavir group and in 43% of lopinavir/ritonavir group, and the rate was also higher than in the higher CD4 cell count strata within the lopinavir/ritonavir treatment group (range: 29–34%). Grades 2–4 treatment-related diarrhea and nausea occurred in more patients receiving lopinavir/ritonavir than atazanavir/ritonavir in all strata. The atazanavir/ritonavir group had more grades 2–4 treatment-related jaundice than in the lopinavir/ritonavir group. These results highlight the importance of tolerability of antiretroviral therapy (ART) in the patients at greatest risk of morbidity and mortality when using regimens of similar potency.

Keywords:

• advanced HIV-1 disease
• atazanavir
• lopinavir

Acknowledgements

We thank the investigators, the study coordinators, and the patients for their contributions. We also acknowledge the contribution of tenofovir disoproxil fumarate and emtricitabine (Truvada) by Gilead. This study was sponsored by Bristol-Myers Squibb. Professional medical writing and editorial assistance was provided by Carolyn Carroll and funded by Bristol-Myers Squibb. Potential conflict of interests: All authors (JU, RY, VW, LS, AF, and DM) are employees and shareholders of Bristol-Myers Squibb. Some of the results described in this paper were presented in a poster: Uy, J., Yang, R., Wirtz, V., Sheppard, L., and Absalon, J., (2009, July). Efficacy and safety of atazanavir/RTV vs. lopinavir/RTV in treatment-naïve patients with advanced disease: CASTLE study 96-week results. Cape Town, South Africa: International AIDS Society. ClinicalTrials.gov, number NCT00272779.