High Dose Atorvastatin Decreases Cellular Markers of Immune Activation without Affecting HIV-1 RNA Levels: Results of a Double-Blind Randomized Placebo Controlled Clinical Trial

(See the editorial commentary by Carr, on pages 751–2.) Background. 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) exhibit antiviral activity against human immunodeficiency virus type 1 (HIV-1) in vitro and may modulate the immune response to HIV infection. Studies evaluating the antiviral activity of statins have yielded conflicting results. Methods. We conducted a randomized, double-blind, placebo-controlled crossover trial to investigate the effect of atorvastatin on HIV-1 RNA (primary objective) and cellular markers of immune activation (secondary objective). HIV-infected individuals not receiving antiretroviral therapy were randomized to receive either 8 weeks of atorvastatin (80 mg) or placebo daily. After a 4–6 week washout phase, participants switched treatment assignments. The study had 80% power to detect a 0.3 log10 decrease in HIV-1 RNA level. Expression of CD38 and HLA-DR on CD4+ and CD8+ T cells was used to measure immune activation. Results. Of 24 randomized participants, 22 completed the study. Although HIV-1 RNA level was unaffected by the intervention (–0.13 log10 copies/mL; P = .85), atorvastatin use resulted in reductions in circulating proportions of CD4+ HLA-DR+ (–2.5%; P = .02), CD8+ HLA-DR+ (–5%; P = .006), and CD8+ HLA-DR+ CD38+ T cells (–3%; P = .03). Reductions in immune activation did not correlate with declines in serum levels of low-density lipoprotein cholesterol. Conclusions. Short-term use of atorvastatin was associated with modest but statistically significant reductions in the proportion of activated T lymphocytes.