Intensified antiretroviral therapy in early HIV infection

2017-11-15

22 treatment-naïve patients with early HIV infection were treated with boosted lopinavir and emtricitabine/tenofovir disoproxil fumarate and randomized to either placebo or intensified therapy with raltegravir and maraviroc. Early HIV infection was defined as documented HIV infection of less than 7 months. The study was a nested substudy within a larger study. The objective of the study was to investigate if intensified therapy could reverse gut immune defects more effectively than standard therapy. Paired blood samples and sigmoid biopsies were performed at baseline and after 48 weeks of therapy. Soluble and mucosal immune activation markers at baseline and after 48 weeks were compared. At baseline gut CD4+ T-cells, Th22 and Th17 cell function were reduced compared to HIV negative controls. Soluble blood markers of inflammation were increased. After 48 weeks the number of CD4+ T cells, had improved but were not normalized, gut Th22 cells normalized while Th17 cell function was unchanged. Soluble markers of inflammation were partly but not completely normalized. There were no differences between the groups that received intensified therapy compared to standard therapy.

Kim et al. AIDS 2017;31:1529-1534

Comment: Intensified therapy with multiple drugs has not shown any benefit in this study or in other studies where the goal was to decrease residual viral replication. Four or five drugs do not do any better than standard of care with 3 active drugs. Presently multiple studies are comparing 2-drug regimens with standard of care and so far there are no indications that 3 drugs do better than 2 drugs. Perhaps “less is more” as long as we avoid monotherapy and combine the right drugs