Combination antiretroviral therapy has substantially reduced HIV morbidity and mortality, but the adverse effects and cost of multiple drugs remain a concern, prompting interest in treatment simplification. Because of its high resistance barrier, boosted lopinavir has been considered an attractive option for simplified maintenance therapy.

In this open-label trial, researchers randomized 60 patients who had viral loads <50 copies/mL for at least 3 months to either continue their triple-drug therapy or switch to lopinavir/r monotherapy. The primary endpoint was treatment failure in the central nervous system (CNS) and/or genital tract.

The trial was stopped prematurely when 6 of the 29 patients on monotherapy — versus none of the 31 on triple-drug therapy — experienced treatment failure in the blood (defined as 2 consecutive plasma viral loads >400 copies/mL). These failures all occurred within the first 6 months of monotherapy and in patients who had nadir CD4 counts <200 cells/mm³; four of the patients developed neurological symptoms. Five patients underwent lumbar puncture after treatment failure in the blood, and all had elevated HIV RNA levels in the cerebrospinal fluid (CSF). An additional 8 of 25 patients on monotherapy had detectable HIV RNA in the CSF, compared with 0 of 15 on triple-drug therapy.

Comment: Protease inhibitor (PI) monotherapy has been associated with higher levels of low-level viremia and more “blips” than combination therapy. This study, although small, adds an intriguing observation to previous data sets, implicating incomplete suppression of HIV replication in the CNS as a risk of PI monotherapy and a cause of frank failure. Detectable HIV RNA in the CSF was not only an important predictor of failure but was also associated, at least in some patients, with overt neurological disease.

Published in Journal Watch HIV/AIDS Clinical Care September 20, 2010