Limb fat and subcutaneous abdominal fat increased significantly after 12 weeks of treatment with pravastatin 40 mg every night (nocte) in HIV-infected men with hypercholesterolaemia [16]; the magnitude of the increase was not related to

its cholesterol-lowering effect, suggesting a mechanism independent of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. This unexpected effect was not observed, however, in another randomized study [17]. We assessed the safety and efficacy of uridine and pravastatin in HIV-infected adults receiving an LPV/r-containing antiretroviral regimen with moderate-to-severe subcutaneous lipoatrophy despite cessation of tNRTI therapy. Subjects were recruited at two university hospitals (the HIV, Immunology and Infectious Diseases Unit, St Vincent’s Hospital, Sydney, Australia, and the HIV Unit, Geneva University selleck products Hospital, Geneva, Switzerland) and in two primary care clinics in Sydney, Australia (Holdsworth House Medical Practice

and Taylor Square Private Clinic) from November 2006 to March 2008. Eligibility criteria were: subcutaneous lipoatrophy in at least two body sites (of moderate or greater severity in at least one site) according to both the patient and their enrolling physician; stable antiretroviral therapy (ART) and plasma HIV viral load<50 HIV-1 RNA copies/mL for at least the preceding 3 months; no grade 3 or 4 laboratory value (except triglycerides for Australian sites); and the provision of written, informed consent. Exclusion criteria were: tNRTI therapy Baf-A1 in the preceding 3 months; prior virological failure on LPV/r; requirement for statin therapy because of known ischaemic cardiovascular disease or clinically significant hyperlipidaemia; statin therapy within the preceding 3 months; current anabolic many steroid, growth hormone or supra-physiological corticosteroid therapy; intolerance to any component of the randomized drugs (including sweeteners and milk protein); and prior use of uridine. The protocol was approved by the Human Research Ethics Committees of

St Vincent’s and Geneva University Hospitals. The study was conducted in accordance with the ethical principles laid out in the Declaration of Helsinki (1996) and Good Clinical Practice guidelines [consolidated guidelines (E6) issued by the International Conference on Harmonization (ICH) in May 1996] and was registered in the Australian and New Zealand Clinical Trials Registry (ANZCTR; number 12608000307303). LPV/r was chosen as the background ‘third drug’ for all participants to reduce treatment heterogeneity and because use of LPV/r has been associated with stable or increasing limb fat mass [7,18]. Participants who were receiving another protease inhibitor or a nonnucleoside reverse transcriptase inhibitor (NNRTI) as the ‘third drug’ were switched from this drug to LPV/r at screening.