Inflammation and Change in Body Weight With Antiretroviral Therapy Initiation in a Multinational Cohort of HIV-Infected Adults.

BackgroundBoth wasting and obesity are associated with inflammation, but the extent to which body weight changes influence inflammation during human immunodeficiency virus infection is unknown.MethodsAmong a random virologically suppressed participants of the Prospective Evaluation of Antiretrovirals in Resource-Limited Settings trial, inflammatory markers were measured at weeks 0, 24, and 48 after antiretroviral therapy (ART) initiation. Associations between both baseline and change in body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and changes in inflammation markers were assessed using random effects models.ResultsOf 246 participants, 27% were overweight/obese (BMI, ≥ 25), and 8% were underweight (BMI < 18.5) at baseline. After 48 weeks, 37% were overweight/obese, and 3% were underweight. While level of many inflammatory markers decreased 48 weeks after ART initiation in the overall group, the decrease in C-reactive protein (CRP) level was smaller in overweight/obese participants (P = .01), and the decreases in both CRP (P = .01) and interleukin 18 (P = .02) levels were smaller in underweight participants. Each 1-unit gain in BMI among overweight/obese participants was associated with a 0.02-log10 increase in soluble CD14 level (P = .05), while each 1-unit BMI gain among underweight participants was associated with a 9.32-mg/L decrease in CRP level (P = .001).ConclusionsBeing either overweight or underweight at ART initiation was associated with heightened systemic inflammation. While weight gain among overweight/obese persons predicted increased inflammation, weight gain among underweight persons predicted reduced inflammation

Inflammation and Change in Body Weight with Antiretroviral Therapy Initiation in a Multinational Cohort of HIV-infected Adults.

BACKGROUND Both wasting and obesity are associated with inflammation, but the extent to which body weight changes influence inflammation in HIV is unknown. METHODS Among a random virologically suppressed participants of the PEARLS trial, inflammatory markers were measured at weeks 0, 24, and 48 post-antiretroviral therapy (ART). Associations between baseline and change in body mass index (BMI) and inflammation changes were assessed using random effects models. RESULTS Of 246 participants, 27% were overweight/obese (BMI≥25 kg/m(2)) and 8% were underweight (BMI<18.5 kg/m(2)) at baseline. After 48 weeks, 37% were overweight/obese and 3% were underweight. While many inflammatory markers decreased 48 weeks after ART in the overall group, the decrease in CRP was smaller in overweight/obese participants (p=0.01) and the decreases in both CRP (p=0.01) and IL-18 (p=0.02) were smaller in underweight participants. Each 1 unit gain in BMI among overweight/obese participants was associated with a 0.02 log10 increase in sCD14 (p=0.05), while each 1 unit BMI gain among underweight participants was associated with 9.32 mg/L decrease in CRP (p=0.001). CONCLUSION Being either overweight or underweight at ART initiation was associated with heightened systemic inflammation. While weight gain among overweight/obese persons predicted increased inflammation, weight gain among underweight persons predicted reduced inflammation

Effect of baseline micronutrient and inflammation status on CD4 recovery post-cART initiation in the multinational PEARLS trial.

Background &amp; aimsNutritional deficiency and inflammation may impact CD4+ T cell recovery during combination antiretroviral therapy (cART), particularly in resource-limited settings where malnutrition is prevalent. The aim of this study was to investigate the relationship of micronutrient and inflammation biomarkers to CD4 recovery after cART initiation.MethodsWe conducted a secondary analysis of a random sub-cohort sample (n&nbsp;=&nbsp;270) from a multinational randomized trial of cART regimen efficacy among 1571 cART-naïve adults. We measured pre-cART serum levels of micronutrients (Vitamin A, B6, B12, D, total carotenoids, selenium, and iron) and inflammation (C-reactive protein, soluble CD14 (sCD14), IFNγ, TNFα, Interleukin-6, and C-X-C motif chemokine 10 (CXCL10/IP10), EndoCab (IgM)) biomarkers. Biomarker status (i.e. micronutrient deficiency vs. sufficiency and elevated vs. low inflammation) was defined using established cutoffs or quartiles. Mixed-effects linear regression models were used to determine the association of baseline (pre-cART) concentrations of individual biomarkers with CD4 recovery through 96 weeks post-cART initiation.ResultsIn models adjusting for time-dependent viral load and baseline CD4 count, age, sex, body mass index, country, treatment regimen, anemia and hypoalbuminemia status, pre-cART vitamin D deficiency was associated with lower CD4 recovery (-14.9&nbsp;cells/mm3, 95% CI:&nbsp;-27.9,&nbsp;-1.8) compared to sufficiency. In contrast, baseline selenium deficiency (20.8&nbsp;cells/mm3, 95% CI: 3.3, 38.3), vitamin A deficiency (35.9&nbsp;cells/mm3, 95% CI: 17.6, 54.3) and high sCD14 (23.4&nbsp;cells/mm3, 95% CI: 8.9, 37.8) were associated with higher CD4 recovery compared to sufficient/low inflammation status.ConclusionsIn summary, baseline vitamin D deficiency was associated with diminished CD4 recovery after cART initiation; impaired CD4 recovery may contribute to the poor clinical outcomes recently observed in individuals with vitamin D deficiency. Vitamin A, selenium and sCD14 were associated with CD4 recovery but future studies are needed to further explore these relationships