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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

2011; Oxford University Press; Volume: 203; Issue: 6 Linguagem: Inglês

10.1093/infdis/jiq115

1537-6613

Anuradha Ganesan, Nancy F. Crum‐Cianflone, Jeanette Higgins, Jing Qin, Catherine Rehm, Julia A. Metcalf, Carolyn Brandt, Jean Vita, Catherine F. Decker, Peter Sklar, Mary Bavaro, Sybil Tasker, Dean Follmann, Frank Maldarelli,

HIV/AIDS drug development and treatment

(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.