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

Abstract

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/mm 3 vs +234 cells/mm 3 , 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.

Two’s a Company, Three’s a Crowd: A Review of Initiating or Switching to a Two-Drug Antiretroviral Regimen in Treatment-Naïve and Treatment-Experienced Patients Living with HIV-1

“…Four randomized, non-inferiority trials were identified of NRTI-inclusive 2DRs in the treatment-naïve population ( Table 1) [10][11][12][13][14]. A small study of (lopinavir/ritonavir) LPV/ r ?…”

British HIV Association guidelines for the treatment of HIV‐1‐positive adults with antiretroviral therapy 2015

“…A post hoc analysis also showed no difference in virological efficacy with respect to the choice of dual NRTI backbone and pre‐treatment CD4 cell count (<200 cells/ μ L) . A study comparing tenofovir‐DF and lopinavir/r to two NRTIs and lopinavir/r failed to demonstrate non‐inferiority of the dual‐therapy arm compared with a standard triple‐therapy combination but numbers were small and the response rates were numerically similar at 51% and 53%, respectively . As lopinavir/r is no longer among the first‐recommended PIs, the dual combination with lamivudine, as used in GARDEL study, has not been considered as an alternative first‐line regimen.…”

Opportunistic Diseases as a Consequence of HIV/AIDS

“…There is no cure to AIDS, a chronic illness [72] but can be a manageable chronic illness when treated with antiretroviral related therapies. There are several adverse side effects with those modes of treatment.…”