infection. Further, the effects of creatine supplementation in combination with PRT on muscle energetics (e.g. mitochondrial function, resistance to fatigue, or intramuscular fat content) are not known in the HIV population, even though these are considered the primary benefits of creatine supplementation. The present study was designed to test the hypothesis that the medical use of creatine supplementation would augment increases in muscle strength derived from PRT in HIV-positive adults. The functional impact and potential mechanisms of these strength gains were also assessed. Methods Protocol The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Checklist S1 and Protocol S1. Ethics The study was approved by the Committees on Human Research at the University of California San Francisco and the San Francisco VA Medical Center. All subjects gave written informed consent. Creatine and HIV+ Patients Participants Forty-three clinically-stable, sedentary HIV-positive subjects (42 men, 1 woman) living in the San Francisco Bay area were recruited by our study coordinators and studied between August 2001 and January 2004 (Figure 1). Subjects using antiretroviral therapy (ART) were required to be on stable regimens for at least 30 days before enrollment and were asked to remain so during the study. Subjects who had received no ART for the preceding 30 days and had no plans to initiate therapy during the study were also eligible. Exclusion criteria included regular resistance exercise training, use of anabolic hormones and other putative ergogenic aids (e.g. amino acids, protein supplements, b-agonists), serum creatinine .1.5 mg/ dl; history of renal disease; creatine kinase (CK) .1.5 times the upper limit of normal (ULN); hemoglobin ,8.5 g/dl; liver transaminase or lactate dehydrogenase levels $56ULN; uncontrolled diarrhea, nausea, or vomiting; impaired oral food intake; untreated hypogo- nadism; pharmacologic use of anabolic or immune modulating therapies; systemic infection within 30 days; history of heart disease; and current pregnancy or lactation. Subjects on stable testosterone replacement for $6 months were eligible. Sample Size Sample size calculations were based on other studies with similar design and allow for a detection of standardized effect sizes Figure 1. CONSORT Diagram showing the disposition of subjects randomized to receive creatine monohydrate or an equivalent number of placebo capsules for 14 weeks. doi:10.1371/journal.pone.0004605.g001 PLoS ONE | www.plosone.org 2 February 2009 | Volume 4 | Issue 2 | e4605