Míguez et al. Journal of the International AIDS Society 2010, 13:25 http://www.jiasociety.org/content/13/1/25 Open Access RESEARCH © 2010 Míguez et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Research Low cholesterol? Don't brag yet ... hypocholesterolemia blunts HAART effectiveness: a longitudinal study María Jose Míguez* 1,2 , John E Lewis 3 , Vaughn E Bryant 3 , Rhonda Rosenberg 2 , Ximena Burbano 4 , Joel Fishman 5 , Deshratn Asthana 3 , Rui Duan 2 , Nair Madhavan 1 and Robert M Malow 2 Abstract 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/mm 3 , 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. Background During the course of HIV disease, disturbances of lipid metabolism have been observed long before the intro- duction of highly active antiretroviral therapy (HAART) and included hypocholesterolemia (HypoCHL; <150 mg/ dl) during early stages of the disease and hypertriglyceri- demia in late phases [1-6]. However, the relationship between lipids and HIV is complex, dynamic, and bi- directional. For example, recent studies have described different mechanisms by which HIV disrupts cholesterol metabolism [7,8]. Conversely, the virus not only needs cholesterol as a structural component of its membrane, but Gag also attaches to cholesterol, and subsequent HIV-1 particle production requires cholesterol-enriched microdomains or rafts [7,8]. By removing cholesterol, researchers have been able to inhibit in vitro HIV-induced syncytium for- mation, reduce the buoyant density of viral particles, interfere with co-receptor expression, and render cells resistant to infection, thus significantly reducing viral infectivity [7,8]. Accordingly, it has been suggested that lipid-lowering drugs could be used to alter HIV infection [7,8]. However, findings are inconsistent. For example, Claxton and colleagues showed that cholesterol under 160 mg/dl is associated with increased risk of HIV infec- tion [9]. Before reducing cholesterol, numerous factors require consideration, particularly in people living with HIV (PLHIV). For instance, cholesterol and lipid rafts integ- rity are essential components for the appropriate func- tion of the immune system and the preservation of health [5,10-12]. Authors of this paper and others have shown * Correspondence: mjmiguez1163@bellsouth.net 1 Institute of Neuroimmune Pharmacology, Florida International University College of Medicine, Miami, FL, USA Full list of author information is available at the end of the article