Endothelial Dysfunction in South African Youth Living With Perinatally Acquired Human Immunodeficiency Virus on Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus (HIV) and antiretroviral therapy (ART) confer cardiovascular disease (CVD) risk in adults with HIV. Few studies have assessed endothelial dysfunction (ED), an early marker of subclinical CVD risk, in youth living with perinatally acquired HIV (YLPHIV). METHODS: Using peripheral arterial tonometry, we compared ED in YLPHIV and age-matched youth without HIV. A reactive hyperemic index ≤1.35 was defined as ED. Eligible participants included those aged 9-14 years and on ART ≥6 months at enrollment. RESULTS: Overall, 431 YLPHIV and 93 youth without HIV with a median age of 14.1 versus 13.9 years, respectively, were included. YLPHIV had a lower BMI z score (BMIZ; -0.2 vs 0.4; P < .01) but higher rates of hypercholesterolemia (10% vs 1%; P = .01) than youth without HIV. Among YLPHIV, mean log viral load (VL) was 4.83 copies/mL with 21.7% having a CD4 count <500 cell/mm3; median duration on ART was 9.8 years with 38% initiating at <2 years of age. YLPHIV had higher rates of ED than youth without HIV (50% vs 34%; P = .01); this relationship persisted after adjusting for age, sex, BMIZ, elevated BP, and hypercholesterolemia (RR, 1.43; P = .02). Among YLPHIV, CD4 count >500 cell/mm3 (RR, 1.04; P = .76), VL (RR, 1.01; P = .78), and current ART class (protease inhibitor based vs nonnucleoside inhibitor based: relative risk, 0.90; P = .186) were not associated with ED after adjustment. CONCLUSIONS: Even after adjusting for physiologic differences, YLPHIV appear to be at increased risk of ED compared with age-matched youth without HIV. These findings have important implications for the life course of YLPHIV who may be at increased risk of premature CVD and complications.

Prevalence and predictors of bone health among perinatally HIV-infected adolescents.

OBJECTIVES: Long-term complications of HIV including low bone mineral density remain a concern. We studied the prevalence and predictors of low bone mineral density among South African perinatally HIV-infected adolescents (PHIVA) on antiretroviral therapy (ART). DESIGN: Cross-sectional analysis. METHODS: Bone health was evaluated by measuring the calcaneus stiffness index among PHIVA on ART. Low stiffness index was defined as z-score less than -2 SD compared with age-matched and sex-matched HIV-uninfected adolescents (HIV-). RESULT: Overall, 407 PHIVA (median age: 14 years; 50.4% female; median age at ART initiation: 4.2 years) and 92 HIV- (median age: 13.7 years; 54.4% female) were included. Median duration on ART was 9.8 years (interquartile range 6.8-11.5) with 38% initiating ART at 2 years or less of age. Stiffness index was lower in PHIVA (-0.19 vs. 0.43, P ≤ 0.001), respectively. During puberty, mean stiffness index increased with Tanner Stage in both PHIVA and HIV- but these increases were larger among HIV-; Tanner Stage II-III (96 vs. 101, P = 0.009) and Tanner Stage IV-V (104 vs. 112, P = 0.001). Among PHIVA, 52 (13%) had low stiffness index. After adjusting for age, sex and Tanner Stage, use of lopinavir/ritonavir [odds ratio (OR) = 2.31, P = 0.012] and viral load more than 50 copies/ml (OR = 2.06, P = 0.023) were associated with increased risk of low stiffness index, while use of efavirenz (OR = 0.41, P = 0.009) was associated with decreased risk of low stiffness index. CONCLUSION: Stiffness index was a significantly lower in PHIVA than in HIV-, especially during puberty. Among PHIVA, detectable viral load and use of lopinavir/ritonavir were risk factors for low stiffness index. Further longitudinal studies are important to determine the clinical implications.