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Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents.

ABSTRACT: OBJECTIVE:Recent studies demonstrate that infection with the HIV-1 is associated with accelerated aging effects in adults according to a highly accurate epigenetic biomarker of aging known as epigenetic clock. However, it is not yet known whether epigenetic age acceleration occurs as early as adolescence in perinatally HIV-infected (PHIV+) youth. DESIGN:Observational study of PHIV and HIV-uninfected adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study. METHODS:The Illumina EPIC array was used to generate blood DNA methylation data from 204 PHIV and 44 age-matched, uninfected (HIV-) adolescents aged 9-12 years old. The epigenetic clock software and method was used to estimate two measures of epigenetic age acceleration. Each participant completed a comprehensive neuropsychological test battery upon enrollment to Cape Town Adolescent Antiretroviral Cohort. RESULTS:HIV is associated with biologically older blood in PHIV+ adolescents according to both measures of epigenetic age acceleration. One of the measures, extrinsic epigenetic age acceleration, is negatively correlated with measures of cognitive functioning (executive functioning, working memory, processing speed). CONCLUSION:Overall, our results indicate that epigenetic age acceleration in blood can be observed in PHIV+ adolescents and that these epigenetic changes accompany poorer cognitive functioning.

SUBMITTER: Horvath S

PROVIDER: S-EPMC6026068 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents.

Horvath Steve S Stein Dan J DJ Phillips Nicole N Heany Sarah J SJ Kobor Michael S MS Lin David T S DTS Myer Landon L Zar Heather J HJ Zar Heather J HJ Levine Andrew J AJ Hoare Jacqueline J

AIDS (London, England) 20180701 11

<h4>Objective</h4>Recent studies demonstrate that infection with the HIV-1 is associated with accelerated aging effects in adults according to a highly accurate epigenetic biomarker of aging known as epigenetic clock. However, it is not yet known whether epigenetic age acceleration occurs as early as adolescence in perinatally HIV-infected (PHIV+) youth.<h4>Design</h4>Observational study of PHIV and HIV-uninfected adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study.<h4>M ...[more]

PMID: 29746298

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Project description:BackgroundThe majority children living with HIV infection now survive into adulthood because of effective antiretroviral therapy (ART), but few data exist on their growth during adolescent years. This study investigated growth patterns and evaluated factors associated with suboptimal growth in adolescents with perinatally-acquired HIV infection.MethodsThis retrospective cohort study included HIV-infected adolescents, aged 13 to 18 years, with at least 5 years of ART follow-up at a large HIV clinic in the Gauteng Province, South Africa. Weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ) and body mass index (BMI)-for-age Z-scores were calculated using World Health Organization (WHO) growth standards. Growth velocity graphs were generated utilising the mean height change calculated at 6-monthly intervals, using all available data after ART initiation, to calculate the annual change. Other collected data included WHO HIV disease staging, CD4%, HIV viral loads (VLs), ART regimens and tuberculosis co-infection.ResultsIncluded were 288 children with a median age of 6.5 years (IQR 4.2;8.6 years) at ART initiation, and 51.7% were male. At baseline the majority of children had severe disease (92% WHO stages 3&4) and were started on non-nucleoside reverse transcriptase inhibitor-based regimens (79.2%). The median CD4% was 13.5% (IQR 7.9;18.9) and median HIV viral load log 5.0 (IQR 4.4;5.5). Baseline stunting (HAZ <-2) was prevalent (55.9%), with a median HAZ of -2.2 (IQR -3.1;-1.3). The median WAZ was -1.5 (IQR -2.5;-0.8), with 29.2% being underweight-for-age (WAZ <-2). The peak height velocity (PHV) in adolescents with baseline stage 3 disease was higher than for those with stage 4 disease. Being older at ART start (p<0.001) and baseline stunting (p<0.001) were associated with poorer growth, resulting in a lower HAZ at study exit, with boys more significantly affected than girls (p<0.001).ConclusionsSuboptimal growth in adolescents with perinatally-acquired HIV infection is a significant health concern, especially in children who started ART later in terms of age and who had baseline stunting and is more pronounced in boys than in girls.

Project description:IntroductionThere are limited data on Tuberculosis (TB) in adolescents with perinatally acquired HIV (APHIV). We examined the incidence and determinants of TB infection and disease in the Cape Town Adolescent Antiretroviral Cohort (CTAAC).MethodsYouth between nine and fourteen years on antiretroviral therapy (ART) for more than six months in public sector care, and age-matched HIV-negative adolescents, were enrolled between July 2013 through March 2015 and followed six-monthly. Data were censored on 31 October 2018. Symptom screening, chest radiograph, viral load, CD4 count, QuantiFERON (QFT) and sputum for Xpert MTB/RIF, microscopy, culture and sensitivity were performed annually. TB infection was defined by a QFT of >0.35 IU/mL. TB diagnosis was defined as confirmed (culture or Xpert MTB/RIF positive) or unconfirmed (clinical diagnosis and started on TB treatment). Analyses examined the incidence and determinants of TB infection and disease.ResultsOverall 496 HIV+ and 103 HIV-negative participants (median age at enrolment 12 years (interquartile range, IQR 10.6 to 13.3) were followed for a median of 3.1 years (IQR 3.0 to 3.4); 50% (298/599) were male. APHIV initiated ART at median age 4.4 years (IQR 2.1 to 7.6). At enrolment, 376/496 (76%) had HIV viral load <40 copies/mL, median CD4 count was 713 cells/mm3 and 179/559 (32%) were QFT+, with no difference by HIV status (APHIV 154/468, 33%; HIV negative 25/91, 27%; p = 0.31). The cumulative QFT+ prevalence was similar (APHIV 225/492, 46%; 95%CI 41% to 50%; HIV negative 44/98, 45%; 95% CI 35% to 55%; p = 0.88). APHIV had a higher incidence of all TB disease than HIV-negative adolescents (2.2/100PY, 95% CI 1.6 to 3.1 vs. 0.3/100PY, 95% CI 0.04 to 2.2; IRR 7.36, 95% CI 1.01 to 53.55). The rate of bacteriologically confirmed TB in APHIV was 1.3/100 PY compared to 0.3/100PY for HIV-negative adolescents, suggesting a fourfold increased risk of developing TB disease in APHIV despite access to ART. In addition, a positive QFT at enrolment was not predictive of TB in this population.ConclusionsHigh incidence rates of TB disease occur in APHIV despite similar QFT conversion rates to HIV-negative adolescents. Strategies to prevent TB in this vulnerable group must be strengthened.

Project description:BackgroundAcross numerous settings, bone mineral density for age and sex is lower in children/adolescents living with perinatally-acquired HIV (PHIV) compared to uninfected peers. We assessed incidences of any fracture/any long bone fracture, and osteoporosis prevalence in PHIV and HIV-exposed uninfected (PHEU) participants in the Pediatric HIV/AIDS Cohort Study (PHACS).MethodologyLifetime history of fracture events from birth up to age 20 years was obtained by chart review and/or interview, including age at fracture, mechanism, and bone(s) fractured. Poisson regression models were fit comparing fracture incidence by HIV status adjusted for age, sex, and race, with effect modification by age (<6, ≥6 yr).ResultsPHIV (N = 412) were older (median 17.5 vs 16.7 yr) and more frequently reported black race (72% vs 61%) than PHEU children/adolescents (N = 206). 17% of PHIV and 12% of PHEU ever reported a fracture. Among children <6 yr, the adjusted incidence rate ratio of ≥1 fracture was higher (7.23; 95% CI 0.98, 53.51) in PHIV than PHEU, but similar among children/adolescents ≥6 years (1.20; 95% CI: 0.77, 1.87). Results were similar for long bone fracture. The most common fracture mechanisms were falling to the ground from a standing height (23.6% PHIV vs 8.8% PHEU) and sports injuries (21.3% vs 32.4%), and the most commonly fractured sites were the forearm and small bones of the wrist/hands. None of the children had osteoporosis.ConclusionsAmong children/adolescents ≥6 yr of age, fractures were similar by perinatal HIV status. Prospective, targeted collection of fracture history will be necessary to determine rates of fracture as PHIV and PHEU age into adulthood.SummaryLifetime fracture history was collected in children/adolescents living with perinatally-acquired HIV (PHIV) and HIV-exposed uninfected (PHEU) children from birth up to age 20 years. Fracture incidence was higher in PHIV compared to PHEU among children <6 years old, but not among older children/adolescents.

Project description:RationaleLung disease is a common cause of mortality and morbidity in HIV-infected adolescents, but there is limited information on the spectrum of lung function impairment in adolescents on antiretroviral therapy.ObjectivesTo investigate lung function in HIV-infected adolescents on antiretroviral therapy in the Cape Town Adolescent Antiretroviral Cohort (Cape Town, South Africa).MethodsA total of 515 South African adolescents, aged 9-14 years, stable on antiretroviral therapy for at least 6 months, underwent baseline lung function testing. Measures included spirometry, nitrogen multiple-breath washout, forced oscillation technique, 6-minute walk test, single-breath carbon monoxide diffusion testing, and bronchodilator response testing. A comparator group of 110 age- and ethnicity-matched HIV-uninfected adolescents was also tested.ResultsFor the HIV-infected adolescents (mean [SD] age 12 [1.6] years, 52% male), the median (interquartile range) duration of antiretroviral therapy was 7.6 (4.6-9.2) years. The median (interquartile range) nadir CD4 was 510.5 (274-903) cells/mm3. HIV-infected adolescents had significantly lower FEV1, FVC, FEV1/FVC, diffusing capacity of carbon monoxide, respiratory system compliance, and functional residual capacity than HIV-uninfected adolescents (P < 0.05 for all associations). HIV-infected adolescents had higher airway resistance and lung clearance index than HIV-uninfected adolescents (P < 0.05 for all associations). Although generally small in magnitude, these differences remained significant after adjusting for age, sex, and height. In addition, age, sex, height, and history of past lower respiratory tract infection or pulmonary tuberculosis were associated with reduced lung function.ConclusionsPerinatally infected South African HIV-infected adolescents on antiretroviral therapy have lower lung function than uninfected adolescents. Prior lower respiratory tract infection or pulmonary tuberculosis is associated with lower lung function.

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Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents.

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Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents.

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