Fractures in children and adolescents living with perinatally acquired HIV.
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ABSTRACT: Background
Across 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).Methodology
Lifetime 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).Results
PHIV (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.Conclusions
Among 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.Summary
Lifetime 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.
SUBMITTER: Jacobson DL
PROVIDER: S-EPMC7484335 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundUsing data from 15 International epidemiology Databases to Evaluate AIDS in Southern Africa sites, we compared the characteristics and outcomes of adolescents living with perinatally acquired HIV (ALPH).MethodsWe included ALPH entering care aged less than 13 years with at least one HIV care visit during adolescence (10-19 years). We compared the characteristics and cross-sectional outcomes: transfer out, loss to follow-up (no visit in the 12 months prior to database closure), mortality, and retention between those who entered care aged less than 10 vs. aged 10-13 years; and explored predictors of mortality after age 13 years using Cox Proportional Hazards models.ResultsOverall, 16 229 (50% female) ALPH who entered HIV care aged less than 10 years and 8897 (54% female) aged 10-13 years were included and followed for 152 574 person-years. During follow-up, 94.1% initiated antiretroviral therapy, with those who entered care aged less than 10 more likely to have initiated antiretroviral therapy [97.9%, 95% confidence interval (CI) 97.6; 98.1%] than those who presented aged 10-13 years (87.3%, 95% CI 86.6; 88.0%). At the end of follow-up, 3% had died (entered care aged <10 vs. 10-13 years; 1.4 vs. 5.1%), 22% were loss to follow-up (16.2 vs. 33.4%), and 59% (66.4 vs. 45.4%) were retained. There was no difference in the risk of dying after the age of 13 years between adolescents entering care aged less than 10 vs. 10-13 years (adjusted hazard ratio 0.72; 95% CI 0.36; 1.42).ConclusionRetention outcomes for ALPH progressively worsened with increasing age, with these outcomes substantially worse among adolescents entering HIV care aged 10-13 vs. less than 10 years.
| S-EPMC7674245 | biostudies-literature
Project description:BackgroundGlobally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in "real-life" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia.Methods and findingsThrough the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria.ConclusionTo our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses.
| S-EPMC5832192 | biostudies-literature
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.
| S-EPMC8789101 | biostudies-literature
Project description:IntroductionAdolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project.MethodsData were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age.ResultsA total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from <3 years in North America and Europe to >7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3 . Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3 . This decline was observed across all regions, in males and females.ConclusionsGrowth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood.
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Project description: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.
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Project description:Children with perinatally acquired HIV (paHIV) remain at an increased risk of pneumococcal infection despite highly active antiretroviral therapy (HAART). Beyond infancy, responses to pneumococcal conjugate vaccine (PCV) remain under-investigated. There are currently no published data on serological response to 13-valent PCV (PCV13) in the HIV-infected populations.We measured pneumococcal serotype-specific IgG in 48 paHIV-infected child patients (CP), 27 young adult healthy controls (AHC) and 30 child healthy controls (CHC). Opsonophagocytic assay (OPA) titres for three PCV13-exclusive serotypes were measured in a subset of children. Serotype-specific IgG was repeated 1 and 6 months following PCV13 vaccination of CP and AHC groups. OPA titres for four serotypes were measured at the 1-month time-point.The majority of CP, CHC and AHC had serotype-specific IgG above 0.35 ??g/ml at baseline, although OPA activity was undetectable for two of the three serotypes studied. Baseline IgG concentrations were significantly lower in CP than AHC for a proportion of serotypes and were strongly predictive of responses to vaccine. After adjusting for baseline, postvaccination IgG concentrations were comparable, although responses to some serotypes were impaired for CP. OPA correlated well with IgG after vaccination. Detectable HIV viral load was associated with significantly lower IgG concentration and OPA titre.Children with paHIV mount a robust serological response to PCV13 for most but not all vaccine serotypes. Viral load suppression with HAART and higher baseline IgG concentration are associated with higher postvaccination antibody levels. This has implications for HAART treatment and vaccination practices.
| S-EPMC4166014 | biostudies-literature
Project description:To describe distributions of immune markers in children and young adults by sex and HIV status, and within groups, investigate associations of immune markers with bone density across Tanner stage. Using data and samples from 353 participants in a cross-sectional study in youth with perinatally acquired HIV (PHIV) and matched HIV-negative controls, distributions of inflammation and activation immune markers were described by sex and HIV status. Correlations and structural equation models (SEM) were used to explore marginal and multivariable associations of the immune markers with bone density and to assess whether patterns of association varied by sex and HIV status. Immune marker distributions did not differ by sex, but there were some differences by HIV status. Correlation patterns among bone, body composition, and immune markers were similar across the sex and HIV status groups. Conclusions from SEMs were limited by small sample sizes, but there was some indication that patterns of association between bone density and certain immune markers differed in male PHIV with more advanced Tanner stage compared to the other three groups. In conclusion, distributions of bone density, body composition, and immune markers may vary by sex and HIV status, although associations among these outcomes within sex and HIV status groups appear similar. Bone density of male PHIV appears to be more negatively affected than females, regardless of female HIV status. Larger longitudinal studies across Tanner stages are needed to further explore potential biological relationships between immune markers and bone density in youth living with HIV.
| S-EPMC7876354 | biostudies-literature
Project description:Chronic HIV-infected children suffer from premature aging and aging-related diseases. Viral replication induces an ongoing inflammation process, with the release of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), the activation of the immune system, and the production of proinflammatory cytokines. Although combined highly active antiretroviral therapy (ART) has significantly modified the natural course of HIV infection, normalization of T and B cell phenotype is not completely achievable; thus, many HIV-infected children display several phenotypical alterations, including higher percentages of activated cells, that favor an accelerated telomere attrition, and higher percentages of exhausted and senescent cells. All these features ultimately lead to the clinical manifestations related to premature aging and comorbidities typically observed in older general population, including non-AIDS-related malignancies. Therefore, even under effective treatment, the premature aging process of HIV-infected children negatively impacts their quality and length of life. This review examines the available data on the impact of HIV and ART on immune and biological senescence of HIV-infected children.
| S-EPMC7246406 | biostudies-literature
Project description:ObjectiveWe investigated dynamics of inflammatory biomarkers in children with perinatally acquired HIV (PHIV) who started antiretrovirals at age less than 3 years and achieved sustained virologic control (HIV plasma RNA <400 copies/ml).DesignThis was a retrospective analysis of inflammatory biomarkers in children enrolled in a randomized trial of early (<3 years of age) PI-based versus NNRTI-based regimens (P1060), who achieved sustained virologic control and participated in a neurodevelopmental follow-up study (P1104s) between ages 5 and 11 years.MethodsWe measured 20 inflammatory biomarkers using ELISA or chemiluminescence at onset of sustained virologic control (Tc) and at P1104s entry (Te).ResultsThe 213 participants had median ages of 1.2, 1.9, and 7 years at antiretroviral initiation, Tc, and Te, respectively, with 138 on protease inhibitor-based and 74 on NNRTI-based regimens at Tc. Eighteen markers decreased and two increased from Tc to Te (Te-Tc). Biomarker subsets, particularly cytokines, the chemokine IP-10, and adhesion molecules sICAM-1 and sVCAM-1, correlated at Tc, Te, and Te-Tc. At Tc, higher biomarker levels were associated with younger age, female sex, HIV plasma RNA at least 750 000 copies/ml, lower nadir CD4 + %, lower nadir weight z scores, and NNRTI-based treatment. Greater Te-Tc biomarker declines were associated with younger age, male sex, higher Tc biomarker levels, lower nadir CD4 + %, and NNRTI-based treatment. Duration of controlled viremia and nadir height z scores showed mixed associations.ConclusionBiomarker expression showed substantial coordination. Most markers decreased after virologic control. Demographic and clinical variables associated with biomarker patterns were identified. Mechanistic studies of these biomarker patterns are needed to inform interventions to control inflammation.
| S-EPMC9262767 | biostudies-literature
Project description:The number of adolescents living with HIV remains high in sub-Saharan Africa with poorer HIV treatment outcomes among adolescents and young adults compared to individuals in other age groups. For adolescents and young adults living with perinatally acquired HIV (AYLPHIV), the transition from pediatric to adult HIV care is a particularly high-risk period. We conducted a qualitative study to understand self-management needs of AYLPHIV in rural, southwestern Uganda as they prepare to transition to adult HIV care in order to inform relevant interventions that can enable AYLPHIV acquire the necessary skills to manage their illness as they age into adulthood. We conducted 60 in-depth interviews with AYLPHIV (n = 30), caregivers (n = 20) and health care providers (n = 10) from the HIV clinic at Mbarara Regional Referral Hospital. We used an interview guide that focused on perceptions about transition to adult HIV care, challenges with transitioning, navigating HIV care, and self-management needs for AYLPHIV (from the perspectives of AYLPHIV, their caregivers, and health care providers). We used thematic analysis to identify themes related to AYLPHIV's self-management skills. We identified several self-management needs that we grouped under two major themes; social support and empowerment for AYLPHIV to assume responsibility for their own health and to navigate adult HIV care independently. The sub-themes under social support were information support, instrumental support, and emotional support as the sub themes while sub-themes under empowerment included self-advocacy skills, interpersonal skills, self-care skills, and disclosure skills. Taken together, these findings indicate that AYLPHIV need to be supported and empowered to maximize their chances of successfully transitioning to adult HIV care. Support comes from peers and caregivers. AYLPHIV require knowledge about their HIV status and empowerment with different skills including: self-advocacy skills, interpersonal skills, self-care skills, and HIV status disclosure skills, in order to assume responsibilities related to independent HIV care.
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