Attenuated T-Lymphocyte Response to HIV Therapy in Individuals Receiving HMG-CoA Reductase Inhibitors

Abstract

Purpose: The protease inhibitor class of antiretroviral agents is associated with the unwanted side effect of hypertriglyceridemia, which is usually treated with either HMG-CoA reductase inhibitors (statins) or fibrates. However, since statin therapy is intrinsically immunomodulatory, we questioned whether the T-cell response of patients who received PI-based therapy plus statin differed from the response of patients on PI therapy alone or on PI therapy with a fibrate. Method: Retrospective cohort study. Results: Thirty-five patients who had received ritonavir/saquinavir (R/S)-based antiretroviral therapy for 5 or more years were evaluated and stratified into four treatment groups: patients on R/S alone (n = 9), patients on R/S and stavudine/lamivudine (d4T/3TC) (n = 10), patients on R/S with or without d4T/3TC and statin (n = 11), or patients on R/S with or without d4T/3TC and fibrate (n = 5). All patients had suppressed levels of viral replication at all time points. T-cell responses were similar in all four groups before they were exposed to lipid-lowering agents. After the addition of lipid-lowering agents, absolute CD4 T-cell responses were lower in the statin group than in all other groups (p < .05), when measured after 6, 12, and 18 months of treatment. Conclusion: These data suggest that T-cell responses are influenced by the choice of anti-lipid agent and suggest that a prospective comparison is needed to determine the clinical relevance of these findings.

Keywords:

• CD4 T-cell response
• fibrates
• HMG-CoA reductase inhibitors
• hyperlipidemia