Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 203, Issue 6, Pages 756-764Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiq115
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Funding
- Infectious Disease Clinical Research Program (IDCRP)
- DoD through the Uniformed Services University of the Health Sciences [IDCRP-015]
- National Institute of Allergy and Infectious Diseases, NIH [Y1-AI-5072]
- National Cancer Institute, National Institutes of Health [NO1-CO-12400]
- National Institute of Allergy and Infectious Diseases
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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 log(10) 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 log(10) 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.
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