Intermittent antiretroviral therapy in patients with controlled HIV infection.

BACKGROUND: To assess the safety of a drug-sparing treatment regimen in patients with high CD4 cell counts and controlled HIV replication under antiretroviral therapy. METHODS: An open-label, non-inferiority study involving 403 adults with CD4 cell counts of 450 x 10(6) cells/l or greater and plasma HIV-1-RNA levels less than 200 copies/ml, randomly assigned to switch to an 8-week off, 8-week on regimen or to continue their antiretroviral regimen. The primary endpoint was the proportion of patients reaching a confirmed CD4 cell count less than 300 x 10(6) cells/l. RESULTS: Over 96 weeks, the proportion of patients meeting this endpoint was non-inferior in the intermittent group (3.6 versus 1.5%, upper bound of the 95% confidence interval of the difference 5.6%). No AIDS-defining event and two non-HIV-related deaths (intermittent arm) were recorded. The median decrease from baseline in the CD4 cell count was greater in the intermittent arm (-155 versus -8 x 10(6) cells/l, P < 0.0001). Minor HIV-related events, mainly lymphadenopathy and mucosal candidiasis, were more frequent in the intermittent group (14 versus 7%, P = 0.04) as were thrombocytopenia. The incidence of grade 3-4 non-HIV-related events and laboratory abnormalities were not statistically different between the groups. At week 96, the proportion of patients with plasma HIV-1-RNA levels less than 400 copies/ml were 81 and 90% in the intermittent (8 weeks after treatment resumption) and continuous groups (P = 0.02), respectively, with similar patterns of HIV resistance genotypes. CONCLUSION: Despite some limitations, an 8-week off and on intermittent treatment regimen appeared clinically safe over 96 weeks while sparing half of the drug exposure.