The Determinants of Elevated Pathobiological Determination of Atherosclerosis in Youth Risk Score in Perinatally HIV-Infected Adolescents in South Africa.

BACKGROUND: Youth living with perinatally acquired HIV infection (YLPHIV) are at risk of developing atherosclerotic cardiovascular disease. METHODS: We determined the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries (CA) and abdominal aorta (AA) risk scores among YLPHIV who are ≥15 years old in Cape Town Adolescent and Antiretroviral Cohort. PDAY score was calculated using non-high-density lipoprotein, high-density lipoprotein cholesterol, hyperglycemia, hypertension, obesity, and smoking; a score ≥1 was considered elevated. HIV viremia was categorized as sustained (SV) = viral load (VL) >50 copies/mL, transient (TV) = mix of VL >50 and ≤50 copies/mL, or sustained-virologic suppression = VL <50 copies/mL throughout the study. Among YLPHIV, logistic models were fit to assess factors associated with elevated PDAY. RESULTS: Overall, 218 YLPHIV [median age 16.8 (interquartile range: 15.9-17.8) years, male 47%] were included. Among YLPHIV, 8% (n = 17) had SV, and 54% (n = 118) had TV. Median antiretroviral therapy (ART) duration was 12 (interquartile range: 8-14) years. Among YLPHIV, 30.3% and 18.4% had elevated PDAY for CA and AA, respectively.Among YLPHIV, SV [adjusted odds ratio (aOR) = 18.4, P < 0.01] and TV (aOR = 2.10, P = 0.04) compared with virologic suppression and ART duration in years (aOR = 1.12, P = 0.03) were associated with elevated CA. Male sex was associated with both elevated CA and AA (aOR = 2.14, P = 0.02, and aOR = 3.43, P = 0.01, respectively) and association of SV with elevated AA (aOR = 3.24, P = 0.09). CONCLUSIONS: A substantial proportion of YLPHIV have PDAY scores reflecting increased aggregate atherosclerotic risk. Among YLPHIV, viremia, lifetime ART duration, and male sex contribute to this risk, highlighting the importance of HIV control and the need to monitor cardiometabolic health.

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.

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.

Echocardiographic Findings in a Cohort of Perinatally HIV-Infected Adolescents Compared with Uninfected Peers from the Cape Town Adolescent Antiretroviral Cohort.

BACKGROUND: Little is known about the cardiac health of perinatally HIV-infected (PHIV+) adolescents on antiretroviral therapy (ART) in sub-Saharan Africa. The authors examined cardiac structure and function in PHIV+ adolescents on ART compared with HIV-uninfected (HIV-) adolescents. METHODS: Echocardiography was performed on PHIV+ and age- and sex-frequency-matched HIV- adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort. Participants were eligible if they were 9 to 14 years of age and had been on ART for ≥6 months. RESULTS: Overall, 474 PHIV+ adolescents (median age, 12 years; 51% boys; mean age at ART initiation, 5 years) and 109 HIV- adolescents (median age, 11.8 years; 45% boys) were included. The mean duration on ART was 7 years, with 37% starting treatment before 2 years of age. Compared with HIV- adolescents, PHIV+ adolescents had higher median Z scores for left ventricular (LV) internal end-diastolic dimension, LV end-systolic posterior wall thickness, and end-systolic interventricular septal thickness. PHIV+ adolescents had a lower median Z score for right ventricular internal end-diastolic dimension as compared with HIV- adolescents. There was no difference in ejection fraction or diastolic function between groups. Later initiation of ART (after 6 years) was associated with increased risk for LV hypertrophy (odds ratio, 2.9; 95% CI, 1.3-6.6; P = .01) compared with those who started ART earlier. PHIV+ adolescents with World Health Organization stage IV HIV infection were at increased risk (odds ratio, 2.2; 95% CI, 1.0-4.6; P = .05) of having LV diastolic dysfunction compared with those with less advanced clinical disease. CONCLUSIONS: This study revealed subtle differences in echocardiographic parameters between PHIV+ and HIV- adolescents. Although these were not clinically significant, starting ART at an older age was a significant risk factor for LV hypertrophy, while more advanced clinical disease was associated with LV diastolic dysfunction.

Insulin Resistance in South African Youth Living with Perinatally Acquired HIV Receiving Antiretroviral Therapy.

To investigate the prevalence of and risk factors for insulin resistance (IR) in a cohort of youth living with perinatally acquired HIV (YLPHIV) receiving antiretroviral treatment (ART). A cross-sectional analysis of IR in YLPHIV and age-matched HIV-uninfected youth enrolled in the Cape Town Adolescent Antiretroviral Cohort. South African youth ages 9-14 years, with perinatally acquired HIV who were on ART for >6 months and age-matched HIV-uninfected adolescents, were eligible. The homeostatic model assessment of insulin resistance (HOMA-IR), calculated from fasting insulin and glucose measurements at enrollment, was used to assess IR. Multiple linear regression was used to examine adjusted associations between HOMA and HIV-related and traditional cardiovascular risk factors. Of 448 adolescents, 385 (85.9%) were YLPHIV; median age was 12.1 years [interquartile range (IQR): 10.8-13.5], and 50.4% were female. Median duration on ART was 7.5 (IQR: 4.5-9.2) years. The prevalence of IR in YLPHIV was 18%. Among YLPHIV, waist circumference (ß = 0.01, p = .01), hypertriglyceridemia (ß = 0.07, p = .01), CD4 count >500 cells/mm3 (ß = 0.08, p = .02), or prior use of abacavir (ß = 0.06, p = .04) were associated with increased HOMA, after adjusting for age, sex, body mass index, and Tanner stage. In a South African cohort of YLPHIV on ART, IR was not significantly different from uninfected adolescents. YLPHIV with traditional cardiovascular risk factors or abacavir exposure may be at higher risk for IR.

Association of Adolescent- and Caregiver-Reported Antiretroviral Therapy Adherence with HIV Viral Load Among Perinatally-infected South African Adolescents.

Accurate measurement of antiretroviral therapy (ART) adherence remains challenging and there are few data assessing the validity of self-reported adherence among perinatally HIV-infected adolescents. We examined adolescent and caregiver reports of adolescent adherence among perinatally-infected adolescents aged 9-14 years in Cape Town, South Africa, and explored factors that may modify associations between reported adherence and elevated viral load (VL). Among 474 adolescents (median age 12.0 years; median duration of ART use 7.5 years), elevated VL and caregiver- and adolescent-report of missed ART doses were common. Elevated VL was particularly prevalent among older, male adolescents. Low-moderate concordance was observed between caregiver and adolescent report. Among adolescents aged ≥ 12 years, caregiver- and adolescent-reported adherence was associated with elevated VL across most items assessed, but few significant associations were observed among adolescents < 12 years of age. Refined adherence measures and tools to identify adolescents who require adherence interventions are needed in this context.