Lopinavir/ritonavir + tenofovir Dual Therapy versus Lopinavir/ritonavir-Based Triple Therapy in HIV-Infected Antiretroviral Naïve Subjects: The Kalead Study

Abstract

Purpose: With reference to the clinical need for simple, potent and safe antiretroviral regimens, Lopinavir/ ritonavir + tenofovir (LPV/r+TDF) two-drug initial regimen was studied for efficacy and safety in HIV-infected patients. Methods: Kalead was a prospective, randomized, open-label, 72-week trial comparing LPV/r+TDF versus LPV/r + two (non-TDF) NRTIs in HIV-infected adults with HIV-RNA >400 copies/mL and any CD4 count. Primary endpoint was the proportion of subjects with HIV-RNA <50 copies/mL at week 72. Results: 152 subjects were randomized. Eleven (15.3%) subjects in the dual therapy arm and seven (8.8%) in the triple therapy arm who did not achieve HIV-RNA <50 copies/mL at least twice prior to and including week 24 were discontinued per protocol (p=0.21). Overall discontinuations were 41.7% and 43.8% in the dual therapy and triple therapyarms. At week 72, 51.4% and 52.5% of subjects in the dual therapy and triple therapy arms had HIV-RNA <50 copies/mL (p=0.89, ITT, NC=F). In an on-treatment analysis, 87.2% and 93.0% of subjects in the dual therapy and triple therapy arms had a HIV-RNA <50 copies/mL (p=0.47). Over 72 weeks of therapy, mean CD4 count increases were greater in the dual therapy arm (+332 cells/mm3 vs +234 cells/mm3, p=0.01). Adherence, overall incidence of adverse events, drugrelated adverse events, and Grade I-IV laboratory abnormalities were comparable between the two arms. Conclusions: A two-drug regimen of LPV/r+TDF suggests sufficient safety and efficacy warranting further investigation. However, high discontinuation rate and study design limitations restrict overall interpretation. © 2010 Pinola M, et al.