Current guidelines for HIV therapy recommend initiating treatment at a CD4 cell count of 500 cells/mm(3). 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/mm(3)) 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/mm(3)) <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/mm(3)), 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.
Trial registration: ClinicalTrials.gov NCT00272779.