Low cholesterol? Don't brag yet ... hypocholesterolemia blunts HAART effectiveness: a longitudinal study

BACKGROUND In vitro studies suggest that reducing cholesterol inhibits HIV replication. However, this effect may not hold in vivo, where other factors, such as cholesterol's immunomodulatory properties, may interact. METHODS Fasting blood samples were obtained on 165 people living with HIV at baseline and after 24 weeks on highly active antiretroviral therapy (HAART). Participants were classified as hypocholesterolemic (HypoCHL; <150 mg/dl) or non-HypoCHL (>150 mg/dl) and were compared on viro-immune outcomes. RESULTS At baseline, participants with HypoCHL (40%) exhibited lower CD4 (197 +/- 181 vs. 295 +/- 191 cells/mm3, p = 0.02) and CD8 (823 +/- 448 vs. 1194 +/- 598 cells/mm3, p = 0.001) counts and were more likely to have detectable viral loads (OR = 3.5, p = 0.01) than non-HypoCHL controls. After HAART, participants with HypoCHL were twice as likely to experience a virological failure >400 copies (95% CI 1-2.6, p = 0.05) and to exhibit <200 CD4 (95% CI 1.03-2.9, p = 0.04) compared with non-HypoCHL. Low thymic output was related to poorer CD4 cell response in HypoCHL subjects. Analyses suggest a dose-response relationship with every increase of 50 mg/dl in cholesterol related to a parallel rise of 50 CD4 cells. CONCLUSIONS The study implicates, for the first time, HypoCHL with impaired HAART effectiveness, including limited CD4 repletion by the thymus and suboptimal viral clearance.