Background:  Plasma HIV-1 RNA and immune activation influence disease progression in HIV⁺ subjects. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) exhibit antiviral activity in vitro and may modulate the immune response to HIV infection by inhibiting protein prenylation. Studies in HIV⁺ subjects evaluating the antiviral activity of statins have yielded conflicting results, and the potential effects of statins on cellular markers of activation have not been investigated.

Methods:  We conducted a randomized, double-blind, placebo-controlled study with a crossover design to investigate the role of statins on HIV-1 RNA and immune activation. HIV-1-infected individuals not on ART were randomized to receive either 8 weeks of an 80-mg dose of atorvastatin daily or placebo daily. After a 4-week wash-out phase, subjects crossed over treatment assignments. The study was designed to have an 80% power to detect a 0.3 log₁₀ decrease in HIV-1 RNA with atorvastatin use. HIV-1 RNA was measured utilizing HIV-b DNA assay. Expression of CD38 and HLA-DR on CD3, CD4, and CD8⁺ T cells was used to measure immune activation.

Results:  Of the 24 subjects randomized, 22 completed the study. Subjects were all male, 63% were Caucasian with a median age of 30 years; median baseline low-density lipoprotein cholesterol (LDL) levels, median CD4 counts, and median HIV-1 RNA levels were 97 mg/dL, 568 cells/µL, and 3.89 log₁₀ HIV-1 RNA copies/mL, respectively. Atorvastatin use was associated with a significant decline in the proportion of CD3⁺ (–4%, p <0.03), CD4⁺ (–2.5%, p <0.02), and CD8⁺ (–4%, p <0.01) cells expressing HLA-DR, without affecting the absolute CD3⁺, CD4⁺, and CD8⁺ counts. Overall, no significant decline in mean HIV-1 RNA levels was detected (–0.15 log₁₀, HIV-1 RNA copies/mL, p = 0.35), although several individual patients did have substantial changes in HIV-1 RNA levels with atorovastatin use. Atorvastatin use resulted in significant declines in median LDL-c levels (–54 mg/dL, p <0.0001), suggesting good adherence to study drug. High-dose atorvastatin was well tolerated with no serious adverse effects observed. Grade1 and 2 elevations in liver function tests were noted with atorvastatin use.

Conclusions:  Despite marked declines in serum lipids significant reductions in HIV viremia were not observed. High-dose atorvastatin reduced the proportion of activated T lymphocytes. The immune modulating effects of statins occur in the absence of detectable antiviral effect.