Induction therapy with trizivir plus efavirenz or lopinavir/ritonavir followed by trizivir alone in naive HIV-1-infected adults.

Author(s): Mallolas J, Pich J, Penaranda M, Domingo P, Knobel H, Pedrol E, Gutierrez F, Barrufet P, Peraire J, Asenjo MA, Vidal F, Gatell JM

Affiliation(s): Infectious Diseases Service, Hospital Clinic IDIBAPS, University of Barcelona, Barcelona, Spain. mallolas@clinic.ub.es

Publication date & source: 2008-01-30, AIDS., 22(3):377-84.

Publication type: Clinical Trial; Comparative Study; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: Induction-maintenance strategies were associated with a low response rate. We compared the virological response with two different induction regimens with trizivir plus efavirenz or lopinavir/ritonavir. METHODS: A randomized, multicentre, open-label clinical trial with 209 antiretroviral-naive HIV-infected patients assigned to trizivir plus either efavirenz or lopinavir/ritonavir during 24-36 weeks. Patients reaching undetectable plasma viral loads during induction entered a 48-week maintenance on trizivir alone. The primary endpoint was the proportion of patients without treatment failure at 72 weeks using an intent to treat (ITT) analysis (switching equals failure). RESULTS: Patients were randomly assigned (efavirenz 104; lopinavir/ritonavir 105), and 114 (55%) entered the maintenance phase (efavirenz 54; lopinavir/ritonavir 60). Baseline characteristics were balanced between groups. The response rate at 72 weeks was 31 and 43% (ITT analysis, P = 0.076) and 63 and 75% (on-treatment analysis, P = 0.172) in the efavirenz and lopinavir/ritonavir arms, respectively. Virological failure occurred in 27 patients: six during induction (efavirenz, three; lopinavir/ritonavir, three; P = 1.0) and 21 during maintenance (efavirenz, 14; lopinavir/ritonavir, seven; P = 0.057). Thirty-four patients in the efavirenz arm switched treatment because of adverse events compared with 25 in the lopinavir/ritonavir arm (P = 0.17). CONCLUSION: Trizivir plus either efavirenz or lopinavir/ritonavir followed by maintenance with trizivir achieved a low but similar response at 72 weeks, with a high incidence of adverse events leading to drug discontinuation during the induction phase in both arms. The study showed a trend towards an increased virological failure rate in the efavirenz arm during the maintenance phase.