N DEXA Results (kg) Lean body mass Limb (arm+leg) LBM Total body fat Trunk fat Limb (arm+leg) fat MRI Results Thigh % EMCL 2 Thigh SAT area (cm ) 2 Calf muscle CSA (cm ) Calf % EMCL 2 Calf SAT area (cm ) 2 Thigh muscle CSA (cm ) 136.7 (24.0) 142.9 (18.3) Baseline Creatine 20 56.0 (7.3) 25.5 (3.8) 13.7 (6.4) 8.2 (4.0) 4.8 (2.2) 4.2 (1.3) 36.2 (18.7) 74.7 (12.7) 4.7 (1.6) 8.2 (5.6) Placebo 20 57.4 (6.6) 26.2 (3.4) 11.8 (4.8) 6.7 (3.1) 4.5 (1.8) 4.9 (2.1) 38.6 (20.3) 73.9 (13.3) 4.6 (1.9) 7.6 (5.4) 19 0.9 (1.9) 0.6 (0.9)* 0.2 (0.8) 0.0 (0.5) 0.2 (0.4) 4.3 (4.8) 20.1 (1.4) 20.8 (2.9) 0.2 (2.6) 0.8 (1.7) 20.3 (1.6) Data are mean (SD). Limb fat is the sum of fat in the arms and legs. The mean differences and 95% confidence intervals between treatment groups of the changes from baseline at weeks 2 and 14 were determined by unpaired t-tests. Differences between groups in changes from baseline that are statistically significant (P,0.05) are highlighted in bold. Asterisks (*) are used to indicate within-group changes from baseline that are statistically significant by paired t-test (P,0.05). Abbreviations: DEXA, dual energy X-ray absorptiometry; MRI, magnetic resonance imaging; CSA, cross-sectional area; SAT, subcutaneous adipose tissue; EMCL, extramyocellular fat (fat infiltration). doi:10.1371/journal.pone.0004605.t003 individuals with HIV infection, as has been reported previously in smaller studies [2–10]. In addition, the rate of PCr recovery following a 15-second MVC improved in the group as a whole. At baseline, average PCr recovery rate (T1/2) was 29 seconds, which is approximately 24% slower than those of healthy young and old adults studied with the same apparatus and using comparable methodology [24]. Following training, PCr recovery rates approached those in healthy untrained adults (TK<23 se- conds[24]). Because PCr recovery under the conditions applied in the present study reflects the capacity for oxidative phosphor- ylation, these data suggest that PRT improved mitochondrial energy metabolism in patients with HIV infection. Overall, these benefits provide further evidence that persons with HIV infection can adapt to a demanding exercise-training program. Table 4. Safety and Biochemical Measurements at Baseline and Changes on Study. Changes wk 0 to wk 2 Differences between groups Mean changes Changes wk 0 to wk 14 (95% CI) Placebo Creatine Creatine Placebo Wk 0 to Wk 2 Table 3. Body Composition at Baseline and Changes on Study. Creatine and HIV+ Patients 19 0.4 (1.2) 20.0 (0.7) 0.2 (0.7) 0.1 (0.5) 0.0 (0.3) 0.7 (4.8) 20.6 (1.6) 2.4 (13.5) 20.1 (2.8) 0.5 (1.9) 0.6 (2.1) Placebo 19 20.4 (1.4) 0.0 (0.1) 215 (84) 65 (199) 24 (23) 0.0 (0.5) 21 (9) 3.0 (6.6) 0.6 (1.5) Changes wk 0 to wk 2 Changes wk 0 to wk 14 Creatine Placebo Creatine Placebo Wk 0 to Wk 2 Wk 0 to Wk 14 Differences between groups Mean changes (95% CI) 17 2.3 (1.4)* 1.1 (0.9)* 0.3 (1.8) 0.0 (1.2) 0.2 (0.6) 12.2 (7.8)* 20.1 (1.5) 20.5 (4.1) 1.5 (3.8) 1.1 (1.9) 0.2 (1.3) 16 0.9 (1.4)* 0.7 (1.1)* 0.4 (2.0) 0.3 (1.5) 0.0 (0.6) 9.3 (8.1)* 21.0 (2.3) 4.7 (14.6) 0.1 (3.5) 0.9 (2.0) 0.4 (0.7) 0.5 (20.5 to 1.5) 0.7 (0.1 to 1.3) 20.0 (20.5 to 0.4) 20.2 (20.5 to 0.1) 0.2 (20.1 to 0.4) 3.6 (20.0 to 7.3) 0.6 (20.6 to 1.7) 0.3 (21.7 to 2.2) 0.3 (21.0 to 1.6) 23.2 (210.3 to 3.9) 25.2 (213.1 to 2.7) 20.9 (22.2 to 0.4) 20.2 (21.0 to 0.6) 1.4 (0.3 to 2.4) 0.5 (20.3 to 1.2) 20.0 (21.4 to 1.3) 20.3 (21.2 to 0.7) 0.2 (20.2 to 0.6) 2.9 (23.3 to 9.1) 0.9 (20.6 to 2.4) 1.4 (21.4 to 4.1) 0.2 (21.2 to 1.7) N Plasma creatine (mg/mL) Serum creatinine (mg/dL) Creatine kinase (U/L) Triglycerides (mg/dL) Cholesterol (mg/dL) Lactate (mmol/L) Glucose (mg/dL) Insulin (mIU/mL) HOMA-IR Baseline Creatine 20 4.6 (1.4) 1.0 (0.2) 111 (51) 169 (89) 183 (47) 1.4 (0.7) 94 (12) 15.9 (5.9) 3.6 (1.2) 20 4.6 (2.2) 1.0 (0.1) 147 (75) 222 (199) 185 (46) 1.1 (0.4) 90 (9) 14.3 (5.2) 3.3 (1.5) 19 26.0 (25.5)* 0.2 (0.2) 20 (57) 91 (362) 1 (19) 0.0 (0.9) 22 (12) 21.6 (6.1) 20.5 (1.5) Data are the mean (SD). All measurements were performed under fasting conditions. The significance of differences between treatment groups in the changes from baseline at weeks 2 and 14 was determined by unpaired t-tests, and differences that are statistically significant (P,0.05) are highlighted in bold. Asterisks (*) are used to indicate within-group changes from baseline that are statistically significant by paired t-test (P,0.05). Abbreviations: HOMA-IR: Homeostasis model assessment of insulin resistance (20). To convert to SI units: creatine mg/mL to mmol/L multiply by 7.625; creatinine mg/dL to mmol/L multiply by 88.4; triglycerides mg/dL to mmol/L multiply by 0.01129; cholesterol mg/dL to mmol/L multiply by 0.02586; glucose mg/dL to mmol/L multiply by 0.05551; insulin mIU/mL to pmol/L multiply by 7.175. doi:10.1371/journal.pone.0004605.t004 PLoS ONE | www.plosone.org 7 February 2009 | Volume 4 | Issue 2 | e4605 22.1 (18.0)* 21.4 (1.4)* 26.4 (12.9 to 39.8) 23.5 (13.6 to 33.4) 17 0.2 (0.2) 20 (61) 78 (165) 26 (22) 0.0 (1.1) 26 (14) 1.2 (10.5) 0.2 (2.5) 16 0.1 (0.1) 8 (64) 218 (75) 210 (18)* 20.1 (0.7) 0 (8) 2.7 (7.3) 0.6 (1.7) 0.2 (0.1 to 0.3) 35 (213 to 84) 26 (2166 to 218) 4 (210 to 18) 20.1 (20.5 to 0.4) 21 (28 to 6) Wk 0 to Wk 14 0.2 (0.1 to 0.3) 12 (233 to 57) 96 (4 to 188) 4 (21 to 19) 20.1 (20.8 to 0.6) 26 (214 to 3) 24.6 (29.1 to 20.2) 21.5 (28.1 to 5.1) 21.0 (22.0 to 0.0) 20.4 (22.0 to 1.2)