Dataset Information

Body Composition Changes After Initiation of Raltegravir or Protease Inhibitors: ACTG A5260s.

ABSTRACT:

Background

Fat gain after antiretroviral therapy (ART) occurs, and its association with protease inhibitors (PIs) is unclear.

Methods

Peripheral and central fat depots and lean mass were measured using standardized and centrally read abdominal CT scans and whole-body dual-energy absorptiometry scans over a 96-week period in human immunodeficiency virus (HIV)-infected treatment-naive participants. The patients were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) in ACTG A5260s, a substudy of A5257. Within arm changes were assessed with signed-rank tests. The 96-week percentage changes in fat and lean mass in the 2 PI arms were not different, thus the PI arms were combined and compared to the RAL arm. Associations between baseline biomarkers and changes in body composition were assessed. All analyses used linear regression models.

Results

328 patients were randomized (90% male, 44% white non-Hispanic). The median age was 36 years, HIV-1 RNA 4.6 log10 copies/mL, and CD4 349 cells/μL. Overall, at week 96, increases in limb fat (13.4%), subcutaneous (19.9%) and visceral abdominal fat (25.8%), trunk fat (18%), and lean mass (1.8%) were apparent (P < .001 for changes within each arm). Changes for all fat and lean outcomes were not different between the PI arms or between the RAL and the combined PI arms. Higher baseline HIV-1 RNA levels were associated with greater gains in peripheral and central fat.

Conclusions

In treatment-naive participants initiating ART with TDF/FTC, no differences in lean mass and regional fat were found with RAL when compared with ATV/r or DRV/r over 96 weeks.

Clinical trials registration

NCT00811954 and NCT00851799.

SUBMITTER: McComsey GA

PROVIDER: S-EPMC4787610 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Rationale & objectiveBioelectrical impedance analysis (BIA) provides a noninvasive assessment of body composition. BIA measures of nutritional (phase angle) and hydration (vector length) status are associated with survival among individuals with chronic kidney disease (CKD), including those receiving maintenance dialysis. However, little is known regarding changes in these parameters with CKD following the high-risk transition to maintenance dialysis.Study designObservational study.Settings & participants427 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study, with BIA measurements performed within 1 year before and after initiation of maintenance dialysis.ExposuresWe calculated the changes in vector length and phase angle for patients with CKD transitioning to maintenance dialysis.OutcomesWe examined the association of changes in vector length and phase angle during the transition to maintenance dialysis with risk for all-cause mortality or nonfatal myocardial infarction, stroke, or heart failure, adjusting for demographics, comorbid conditions, and nutritional parameters.ResultsMean age was 58 ± 12 years and mean estimated glomerular filtration rate using the CKD Epidemiology Collaboration equation before dialysis initiation was 17.0 ± 8.7 mL/min/1.73 m2. After covariate adjustment, mean changes in vector length and phase angle were 18 (95% CI, 7 to 30) Ω/m and -0.6 (95% CI, -1.3 to 0.1 ), respectively. Changes in both BIA parameters were not associated with risk for heart failure, stroke, myocardial infarction, or all-cause mortality: HR, 1.02 (95% CI, 0.91-1.14) per 1-SD increment in change for vector length and HR, 1.11 (95% CI, 0.88-1.41) per 1-SD increment in change for phase angle.LimitationsObservational study, relatively small sample size.ConclusionsIn a multicenter cohort of patients with CKD who progressed to kidney failure, the transition to maintenance dialysis was associated with changes in body composition reflecting poorer cellular integrity and improved volume control. However, these longitudinal changes were not associated with adverse clinical events after dialysis initiation.

Project description:We have previously shown that 24 young lean men (12 pairs of identical twins) subjected to a standardized 353?MJ (84?000?kcal) overfeeding protocol over 100 days exhibited individual differences in body weight and composition gains. The mean (+s.d.) gains in fat mass (FM) and fat-free mass (FFM) were 5.4+1.9?kg and 2.7+1.5?kg for a total body energy (BE) gain of 221+75?MJ, representing 63% of the energy surplus consumed. We report here on the most important baseline correlates of these overfeeding-induced changes with the aim of identifying biomarkers of the response.Baseline maximal oxygen uptake per kg body mass was negatively correlated with gains in weight, FM and BE (all P<0.05). Enzyme activities indicative of skeletal muscle oxidative potential correlated with gains in FM and BE (all P<0.05). Baseline thyroid-stimulating hormone levels in response to thyrotropin-releasing hormone stimulation correlated positively with changes in FM-to-FFM ratio (P<0.05). Plasma concentrations of androstenediol sulfate, dehydroepiandrosterone and 17-hydroxy pregnenolone were negatively correlated with gains in FM and BE (0.01<P<0.05), whereas the level of estrone was negatively correlated and androsterone glucoronide was positively correlated with FFM gains (P<0.05). Baseline leptin and abdominal fat cell size correlated positively with gains in weight, FM and BE (P<0.05). When compared with the six highest BE gainers, the six lowest gainers exhibited higher thermic effect of a meal (TEM) and plasma levels of total testosterone, cortisol, estradiol, androstenedione and androstenediol sulfate (all P<0.05). High baseline levels of total TEM, testosterone and androstenediol sulfate were associated with lower FM gains, whereas high baseline levels of FT4 and estrone were found in low-FFM gainers.Although none of the variables exerted individually an overwhelmingly strong influence on overfeeding-induced changes, baseline FFM, maximal oxygen uptake, muscle oxidative capacity, androgens and leptin levels were the most consistent significant biomarkers of the responsiveness to chronic overfeeding.