Long Zhang

Changes in weight and weight distribution across the lifespan among HIV-infected and -uninfected men and women

AbstractExamine body composition changes across the lifespan of HIV-infected compared to uninfected adults. Longitudinal study of antiretroviral therapy (ART)-treated HIV-infected and uninfected participants from the Multicenter AIDS Cohort Study and Womens Interagency HIV Study. Body mass index (BMI), waist (WC), hip circumference (HC), and waist-to-height ratio (WHtR) measured at semiannual visits from 1999 to 2014. The age effect on outcomes over time was investigated using multivariate, piecewise, linear mixed-effect regression models adjusted for demographics, substance use, and comorbidities. Person-visits from 2363 men (1059 HIV-infected/1304 HIV-uninfected) and 2200 women (1455 HIV-infected/745 HIV-uninfected), median ages 45 [IQR 39,51] and 40 [32,46], respectively, were included. BMI gains were slower among HIV-infected participants of 40 years or less (P < 0.001), similar between HIV-infected and uninfected persons 40 to 60 years of age, and plateaued after age 60 in both groups. WC and WHtR increased across the age spectrum (P < 0.001) regardless of HIV serostatus, with significantly greater gains in HIV-infected men more than 60. Black race and Hispanic ethnicity were associated with greater BMI and WC. Lower BMI, WC, hip circumference, and WHtR were associated with hepatitis C infection among women only, and with substance use among all participants, and with lower CD4+ cell count and shorter ART duration among HIV-infected participants. Slower BMI gain among younger HIV-infected adults may be partly explained by substance use and hepatitis C infection, and suggests that lower BMI does not represent improved health. Further analysis of muscle and fat abundance and quality will advance understanding of metabolic risk over the lifespan, a key to reducing morbidity in an aging population.

Predictors of electrocardiographic QT interval prolongation in men with HIV

Objective HIV-infected (HIV+) individuals may be at increased risk for sudden arrhythmic cardiac death. Some studies have reported an association between HIV infection and prolongation of the electrocardiographic QT interval, a measure of ventricular repolarisation, which could potentiate ventricular arrhythmias. We aimed to assess whether HIV+ men have longer QT intervals than HIV-uninfected (HIV−) men and to determine factors associated with QT duration. Methods We performed resting 12-lead ECGs in 774 HIV+ and 652 HIV− men in the Multicenter AIDS Cohort Study (MACS). We used multivariable linear and logistic regression analyses to assess associations between HIV serostatus and Framingham corrected QT interval (QTc), after accounting for potential confounders. We also determined associations among QTc interval and HIV-related factors in HIV+ men. In a subgroup of participants, levels of serum markers of inflammation were also assessed. Results After adjusting for demographics and risk factors, QTc was 4.0 ms longer in HIV+ than HIV− men (p<0.001). Use of antiretroviral therapy (ART), specific ART drug class use and other HIV-specific risk factors were not associated with longer QTc. Among the subgroup with inflammatory biomarker measurements, higher interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and B-cell activating factor levels were independently associated with longer QTc and their inclusion partially attenuated the HIV effect. Conclusions HIV+ men had longer QTc, which was associated with higher levels of systemic inflammatory factors. This longer QTc may contribute to the increased risk for sudden arrhythmic cardiac death in some HIV+ individuals.

Abdominal obesity, sarcopenia, and osteoporosis are associated with frailty in men living with and without HIV

Objective: The relationships between frailty and body composition in older adults with HIV infection are poorly understood. We sought to describe associations between frailty and measures of body composition among adult men with HIV and without HIV. Design/Methods: Men with and without HIV (age 50–69 years) in the Multicenter AIDS Cohort Study (MACS) Bone Strength Substudy were included if evaluated for frailty (by Fried phenotype) and body composition [BMI, waist circumference, abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, sarcopenia, and osteopenia/osteoporosis]. All participants with HIV infection were on antiretroviral therapy. Multivariate multinomial logistic regression models were used to determine associations of frailty with body composition. Results: A total of 399 men, including 199 men with HIV and 200 men without HIV, both with median age 60 years, constituted our study population. Frailty prevalence was 16% (men with HIV) vs. 8% (men without HIV). HIV serostatus was associated with a 2.43 times higher odds of frailty (P = 0.01). Higher waist circumference, VAT, sarcopenia, and femoral neck osteoporosis were associated with increased odds of frailty (aOR 4.18, 4.45, 4.15, and 13.6, respectively, and all P < 0.05); BMI and SAT were not. None of these measures presented a differential association with frailty by HIV serostatus (all P > 0.20). Conclusion: Higher abdominal obesity and sarcopenia were associated with frailty among men with and without HIV. Assessment of these body composition parameters may help detect frailty in the clinical setting.

Vitamin D status and immune function reconstitution in HIV-infected men initiating therapy

Objective: Despite effective antiretroviral therapy (HAART) and durable viral suppression, many HIV-infected individuals still do not achieve CD4+ cell count (CD4+) normalization. Vitamin D has immunoregulatory functions, including inducing the development of T cells and higher levels may improve CD4+ rebound. Design: Longitudinal study of men from the Multicenter AIDS Cohort Study who virally suppressed following HAART initiation and had pre-HAART and post-HAART 25(OH)D and 1,25(OH)2D measurements and repeated measures of CD4+. Methods: CD4+ rebound was modeled using a nonlinear mixed effects model. We estimated the adjusted effect (adjusted for pre-HAART antiretroviral exposure, black race, age and CD4+ at HAART initiation) of pre-HAART and post-HAART vitamin D metabolite levels on the rate of CD4+ increase and final CD4+ plateau. Results: Among the 263 HIV-infected HAART initiators with pre-HAART vitamin D measurements, a 1-SD higher pre-HAART 25(OH)2D level was associated with a 9% faster rate of rise (P = 0.02) but no gain in final CD4+ plateau. In contrast, a 1-SD higher 1,25(OH)2D level was associated with a 43-cell lower final CD4+ (P = 0.04). Among 560 men with post-HAART measurements, findings were similar to those for pre-HAART 25(OH)2D with 1-SD higher level associated with faster rate of rise but no improvement in final CD4+. Conclusion: We found no evidence that higher vitamin D metabolite levels pre-HAART or post-HAART are associated with better CD4+ outcomes among HIV-infected HAART initiators. However, the value of pre-HAART 1,25(OH)2D levels as an indicator of immune response dysregulation could be further explored.