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Introduction: Adolescents are a unique and sometimes neglected group in the planning of healthcare services. This is the case in many parts of sub‐Saharan Africa, where more than eight out of ten of the world's HIV‐infected adolescents live. Although the last decade has seen a reduction in AIDS‐related mortality worldwide, largely due to improved access to effective antiretroviral therapy (ART), AIDS remains a significant contributor to adolescent mortality in sub‐Saharan Africa. Although inadequate access to ART in parts of the subcontinent may be implicated, research among youth with HIV elsewhere in the world suggests that suboptimal adherence to ART may play a significant role. In this article, we summarize the epidemiology of HIV among sub‐Saharan African adolescents and review their adherence to ART, emphasizing the unique challenges and factors associated with adherence behaviour. Methods: We conducted a comprehensive search of online databases for articles, relevant abstracts, and conference reports from meetings held between 2010 and 2014. Our search terms included “adherence,” “compliance,” “antiretroviral use” and “antiretroviral adherence,” in combination with “adolescents,” “youth,” “HIV,” “Africa,” “interventions” and the MeSH term “Africa South of the Sahara.” Of 19,537 articles and abstracts identified, 215 met inclusion criteria, and 148 were reviewed. Discussion: Adolescents comprise a substantial portion of the population in many sub‐Saharan African countries. They are at particular risk of HIV and may experience worse outcomes. Although demonstrated to have unique challenges, there is a dearth of comprehensive health services for adolescents, especially for those with HIV in sub‐Saharan Africa. ART adherence is poorer among older adolescents than other age groups, and psychosocial, socio‐economic, individual, and treatment‐related factors influence adherence behaviour among adolescents in this region. With the exception of a few examples based on affective, cognitive, and behavioural strategies, most adherence interventions have been targeted at adults with HIV. Conclusions: Although higher levels of ART adherence have been reported in sub‐Saharan Africa than in other well‐resourced settings, adolescents in the region may have poorer adherence patterns. There is substantial need for interventions to improve adherence in this unique population., Introduction Although significant progress has been achieved in understanding the pathogenic mechanisms, transmission, clinical features and complications of HIV/AIDS, the disease remains a global menace with large numbers of new [...]

HIV-related enacted stigma and social problems may increase risk for depression and/or behavioral problems among adolescents and young adults with perinatal HIV(AYA-PHIV), yet few studies have explored stigma in AYA-PHIV residing in low-to-middle income regions, including Southeast Asia. We assessed HIV-related enacted stigma and social problems in AYA-PHIV who participated in the RESILIENCE study (clinicaltrials.gov identification: U19AI53741) in Thailand and Cambodia using specific questions during structured in-person interviews. Depression was measured by the Child Depression Inventory for children <15 years, or the Center for Epidemiologic Studies Depression Scales for youth ≥15 years); behavioral problems were measured by the Child Behavior Checklist (CBCL-caregiver report). Among 195 AYA-PHIV (median age 16.9 years), 25.6% reported a lifetime experience of enacted stigma, while 10.8% experienced social problems due to HIV infection. The frequency of depressive symptoms was nearly two-fold higher among AYA-PHIV with compared to those without HIV-related enacted stigma (34.7% vs. 16.0%, p = 0.005). Caregiver-reported behavioral problems were detected in 14.6% of all AYA-PHIV, with no differences between those with and without HIV-related enacted stigma. Low household income and caregiver mental health problems were independent risk factors for depressive symptoms; HIV-related enacted stigma was also associated with increased risk, warranting targeted services to support AYA-PHIV. [ABSTRACT FROM AUTHOR]

Background: Cognitive and behavioral impairment are common in children living with perinatally acquired HIV (pHIV) and children exposed to HIV in utero but uninfected (HEU). Methods: We sought to determine the prevalence of adverse behavioral symptomatology using a Thai-translated and validated version of the SNAP-IV questionnaire and assess cognitive function utilizing the Children's Color Trails Test, Delis-Kaplan Executive Function System, and the Wechsler Intelligence Scales, in our cohort of Thai adolescents (10–20 years old) with well-controlled pHIV compared to HEU and HIV-unexposed, uninfected youth. We then evaluated the interaction between HIV status, behavioral impairment, and executive function outcomes independent of demographic variables. Results: After controlling for demographic factors of age and household income, adolescents with pHIV had higher inattentive symptomatology and poorer neuropsychological test scores compared to uninfected controls. Significant interactions were found between inattention and executive function across multiple neurocognitive tests. Conclusions: Behavioral impairment and poor executive functioning are present in adolescents with well-controlled pHIV compared to HIV-uninfected matched peers. The SNAP-IV questionnaire may be a useful tool to identify those with attentional impairment who may benefit from further cognitive testing in resource-limited settings. [ABSTRACT FROM AUTHOR]

Although behavioral problems have been observed in children and adolescents with perinatally-acquired HIV infection (PHIV), behavioral information regarding younger PHIV children are scarce. This study aims to identify behavioral problems in PHIV and HIV-exposed uninfected (HEU) children and to evaluate factors associated with such problems. A prospective study of PHIV and HEU young children was conducted. Behavioral problems were assessed with the Child Behavior Checklist (CBCL) at baseline and 12 months later among children aged 18–60 months old. The Patient Health Questionnaire-9 and the Parenting Styles & Dimensions Questionnaire identified primary caregivers' symptoms of depression and parenting styles, respectively, at both visits. Chi-squared analyses were used to compare the prevalence of behavioral problems between groups. Factors associated with behavioral problems were analyzed by logistic regression. From 2016 to 2017, 121 children (41 PHIV and 80 HEU) were assessed with no significant differences in prevalence of Total, Internalizing, Externalizing, and Syndrome scales problems between PHIV and HEU at both visits (p > 0.5). Primary caregivers' depression and lower education in addition to authoritarian and permissive parenting styles were significantly related to child behavioral problems. Family-centered care for families affected by HIV, including positive parenting promotion, mental health care, and education are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Across the globe, children born with perinatal HIV infection (PHIV) are reaching adolescence and young adulthood in large numbers. The majority of research has focused on biomedical outcomes yet there is increasing awareness that long-term survivors with PHIV are at high risk for mental health problems, given genetic, biomedical, familial and environmental risk. This article presents a review of the literature on the mental health functioning of perinatally HIV-infected (PHIV+) adolescents, corresponding risk and protective factors, treatment modalities and critical needs for future interventions and research. Methods: An extensive review of online databases was conducted. Articles including: (1) PHIV+ youth; (2) age 10 and older; (3) mental health outcomes; and (4) mental health treatment were reviewed. Of 93 articles identified, 38 met inclusion criteria, the vast majority from the United States and Europe. Results: These studies suggest that PHIV+ youth experience emotional and behavioural problems, including psychiatric disorders, at higher than expected rates, often exceeding those of the general population and other high-risk groups. Yet, the specific role of HIV per se remains unclear, as uninfected youth with HIV exposure or those living in HIV- affected households displayed similar prevalence rates in some studies, higher rates in others and lower rates in still others. Although studies are limited with mixed findings, this review indicates that child-health status, cognitive function, parental health and mental health, stressful life events and neighbourhood disorder have been associated with worse mental health outcomes, while parent-child involvement and communication, and peer, parent and teacher social support have been associated with better function. Few evidence-based interventions exist; CHAMP+, a mental health programme for PHIV+ youth, shows promise across cultures. Conclusions: This review highlights research limitations that preclude both conclusions and full understanding of aetiology. Conversely, these limitations present opportunities for future research. Many PHIV+ youth experience adequate mental health despite vulnerabilities. However, the focus of research to date highlights the identification of risks rather than positive attributes, which could inform preventive interventions. Development and evaluation of mental health interventions and preventions are urgently needed to optimize mental health, particularly for PHIV+ youth growing up in low-and-middle income countries. Keywords: mental health; psychiatric disorders; emotional and behavioural problems; perinatal HIV infection; adolescence; paediatric HIV., Introduction With widespread use of highly active antiretroviral therapy (HAART), children born with perinatal HIV infection (PHIV +) are reaching adolescence and young adulthood in large numbers, such that paediatric [...]

Youth perinatally HIV infected (PHIV) or HIV exposed, but uninfected (PHEU), are aging into adolescence and adulthood with multiple complex risk factors for mental health (MH) problems and poor MH treatment utilization. Our aims were to estimate prevalence of MH diagnoses, clinically significant symptoms, and MH treatment utilization among youth with PHIV and among PHEU youth, 10–22 years old. We also aimed to identify correlates of diagnoses and treatment utilization. Analyses of data from standardized interviews, behavioral assessments, and chart review of 551 youth revealed that 36% had a previous or current MH diagnosis, with no significant HIV status group differences. Prevalence of clinically significant symptoms was 15% for both groups, of whom a third had no diagnosis, and half were not receiving treatment. Among youth with a current MH diagnosis, those with PHIV had greater utilization of services than PHEU youth (67% vs. 51%; p = 0.04). Factors associated with MH diagnoses and/or treatment utilization included caregiver characteristics, age and sex of child, HIV status, and stressful life events. Prevalence of MH diagnoses was higher than in the general population, but lower than in similar perinatally HIV-exposed cohorts, with some unmet service needs, particularly in PHEU youth. Family characteristics warrant careful consideration in early diagnosis and treatment of MH problems among youth affected by HIV. [ABSTRACT FROM AUTHOR]

BACKGROUND. Most evaluations of adherence to antiretroviral therapy in children with HIV infection have focused on validation of adherence measures via their association with virological outcomes. However, few studies have fully explored associations with other factors to guide development of adherence interventions. METHODS. In this study, we examined the relationship of self-reported medication adherence to health, demographic, and psychosocial characteristics of children and their caregivers, using data from an ongoing multicenter prospective observational study of long-term outcomes of HIV infection conducted by the Pediatric AIDS Clinical Trials Group. Child and caregiver characteristics were evaluated for association with adherence via univariate and multiple logistic regression models. RESULTS. Of the 2088 children and adolescents, 84% reported complete adherence to antiretroviral therapy medications over the past 3 days. The median viral load was ~10 times higher among nonadherent than adherent children, and the strength of this association increased with age. Factors associated with at least marginally significant increases in nonadherence in a multiple logistic regression model included increasing age in years, female gender, detectable HIV viral load, occurrence of recent stressful life events, repeating a grade in school, self-assessment of adherence by the subject, and diagnosis of depression or anxiety. Having an adult other than the biological parent as the primary caregiver, using a buddy system to remember to take antiretroviral therapy medications, higher caregiver education level, previous adherence assessments, and taking antipsychotic medications were each associated with improved adherence. After controlling for these characteristics, there was no significant association of adherence with race, knowledge of HIV status, medication burden, CD4 percentage, or current antiretroviral therapy. CONCLUSIONS. Rates of self-reported adherence were relatively high and were influenced by multiple child and family characteristics. These findings identify targets for adherence interventions and highlight the importance of evaluating and supporting the family environment to optimize adherence. KEYWORDS. medication adherence, HIV, family environment, child behavior, adolescents, stressful life events. PEDIATRICS 2006;118:e1745-e1757. URL: www.pediatrics.org/cgi/doi/10.1542/peds.2006-0493, Paige L. Williams, PhD, Deborah Storm, PhD, RN, Grace Montepiedra, PhD, Sharon Nichols, PhD, Betsy Kammerer, PhD, Patricia A. Sirois, PhD, John Farley, MD, Kathleen Malee, PhD, for the PACTG [...]

Background: Little is known regarding effects of perinatally acquired HIV infection (PHIV) on longitudinal change in memory and executive functioning (EF) during adolescence despite the importance of these skills for independence in adulthood. Methods: PHIV (n = 144) and perinatally HIV-exposed uninfected youth (PHEU, n = 79), ages 12-17, completed standardized tests of memory and EF at baseline and 2 years later. Changes from baseline for each memory and EF outcome were compared between PHEU and PHIV youth with (PHIV/C, n = 39) and without (PHIV/non-C, n = 105) history of CDC class C (AIDS-defining) diagnoses. Among PHIV youth, associations of baseline and past disease severity with memory and EF performance at follow-up were evaluated using adjusted linear regression models. Results: Participants were primarily black (79%); 16% were Hispanic; 55% were female. Mean memory and EF scores at follow-up generally fell in the low-average to average range. Pairwise comparison of adjusted mean change from baseline to follow-up revealed significantly greater change for PHIV/non-C compared with PHEU youth in only one verbal recognition task, with a difference in mean changes for PHIV/non-C versus PHEU of 20.99 (95% CI: 21.80 to 20.19; P = 0.02). Among youth with PHIV, better immunologic status at baseline was positively associated with follow-up measures of verbal recall and recognition and cognitive inhibition/flexibility. Past AIDS-defining diagnoses and higher peak viral load were associated with lower performance across multiple EF tasks at follow-up. Conclusions: Youth with PHIV demonstrated stable memory and EF during a 2-year period of adolescence, allowing cautious optimism regarding long-term outcomes. [ABSTRACT FROM AUTHOR]

Background. Combination antiretroviral therapy has led to increased survival among youth with perinatally acquired HIV (PHIV). However, cognitive deficits continue to be common. Histopathological studies in adults have found HIV concentrated in subcortical structures, which are involved in sensory processing, movement, and higher-order cognition that emerges with development. Methods. We conducted magnetic resonance imaging and cognitive testing in 40 youth with PHIV at one site of the Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study. We collected HIV disease-severity measures and substance-use reports. Subcortical volume and shape deformation were generated with FreeSurfer-Initiated Large Deformation Diffeomorphic Metric Mapping. Inward shape deformation was defined as negative displacement. We evaluated associations of subcortical shape deformation with past HIV severity after adjustment for sex, age at neuroimaging, age at HIV severity marker, and substance use. We examined associations between subcortical deformation and cognitive function. Results. Negative correlations between shape deformation and peak HIV viral load (VL) were found in clusters in the caudate tail, globus pallidus, lateral putamen, and anterior and medial thalamus. Positive correlations between shape deformation and nadir CD4-positive T-lymphocyte percentage (CD4%) were found in clusters in the medial and posterior thalamus. Inward deformation in caudate and thalamic clusters correlated with worse cognition. Conclusions. Youth with PHIV have demonstrable subcortical shape deformation related to past HIV severity and cognition; inward deformation was associated with higher peak VL, lower nadir CD4%, and worse cognition. Identifying subcortical deformation may inform clinical practice for early intervention to help improve cognitive outcomes and assess the neuroefficacy of combination antiretroviral therapy in youth with PHIV. [ABSTRACT FROM AUTHOR]

OBJECTIVES. The purpose of this work was to examine the effects of HIV infection and the impact of highly active antiretroviral treatment with protease inhibitors on neuro-developmental functioning during the [...]

Objective. Psychiatric manifestations of pediatric human immunodeficiency virus (HIV) infection have been described. However, data on severe sequelae requiring hospitalization among this population have not been reported. Methods. The Pediatric Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group (PACTG) 219C is a prospective cohort study designed to examine long-term outcomes among HIV-infected children and HIV-uninfected infants born to HIV-infected women. Children with HIV infection who have enrolled in PACTG 219C are examined quarterly, with collection of clinical and laboratory data. Hospitalizations and diagnoses for all participants between September 2000 (when enrollment into PACTG 219C was started) and December 2002 were reviewed. Results. Among 1808 HIV-infected participants who were Conclusions. Children with HIV/AIDS are at increased risk for psychiatric hospitalizations during childhood and early adolescence, compared with the general pediatric population. Knowledge of HIV seropositivity status and recent significant life events were significantly associated with increased risks of admission in this population. Pediatrics 2004;113:e544-e551. URL: http: //www.pediatrics.org/cgi/content/full/113/6/e544; HIV/ AIDS, pediatrics, psychiatric hospitalization, psychologic distress, disclosure, proportional hazards regression., Denise M. Gaughan, MPH; Michael D. Hughes, PhD; James M. Oleske, MD, MPH; Kathleen Malee, PhD; Carol A. Gore; and Sharon Nachman, MD, for the Pediatric AIDS Clinical Trials Group [...]

Poor adherence to antiretroviral therapy (ART) contributes to disease progression and emergence of drug-resistant HIV in youth with perinatally acquired HIV infection (PHIV +), necessitating reliable measures of adherence. Although electronic monitoring devices have often been considered the gold-standard assessment in HIV research, they are costly, can overestimate nonadherence and are not practical for routine care. Thus, the development of valid, easily administered self-report adherence measures is crucial for adherence monitoring. PHIV+youth aged 7–16 (n= 289) and their caregivers, enrolled in a multisite cohort study, were interviewed to assess several reported indicators of adherence. HIV-1 RNA viral load (VL) was dichotomized into >/≤400 copies/mL. Lower adherence was significantly associated with VL >400 copies/mL across most indicators, including ≥1 missed dose in past seven days [youth report: OR = 2.78 (95% CI, 1.46–5.27)]. Caregiver and combined youth/caregiver reports yielded similar results. Within-rater agreement between various adherence indicators was high for both youth and caregivers. Inter-rater agreement on adherence was moderate across most indicators. Age ≥13 years and living with biological mother or relative were associated with VL >400 copies/mL. Findings support the validity of caregiver and youth adherence reports and identify youth at risk of poor adherence. [ABSTRACT FROM AUTHOR]

Among 330 perinatally infected youths (mean age, 13.5 years), 28% reported sexual intercourse. Most reported unprotected sex and human immunodeficiency virus nondisclosure to first partners. Viral resistance to ≥1 antiretroviral medication was detected in 81% of sexually active youths with viral load ≥5000 copies/mL.Background. Factors associated with initiation of sexual activity among perinatally human immunodeficiency virus (HIV)–infected (PHIV+) youth, and the attendant potential for sexual transmission of antiretroviral (ARV) drug-resistant HIV, remain poorly understood.Methods. We conducted cross-sectional and longitudinal analyses of PHIV+ youth aged 10–18 years (mean, 13.5 years) enrolled in the US-based Pediatric HIV/AIDS Cohort Study between 2007 and 2009. Audio computer-assisted self-interviews (ACASI) were used to collect sexual behavior information.Results. Twenty-eight percent (95% confidence interval [CI], 23%–33%) (92/330) of PHIV+ youth reported sexual intercourse (SI) (median initiation age, 14 years). Sixty-two percent (57/92) of sexually active youth reported unprotected SI. Among youth who did not report history of SI at baseline, ARV nonadherence was associated with sexual initiation during follow-up (adjusted hazard ratio, 2.87; 95% CI, 1.32–6.25). Youth living with a relative other than their biological mother had higher odds of engaging in unprotected SI than those living with a nonrelative. Thirty-three percent of youth disclosed their HIV status to their first sexual partner. Thirty-nine of 92 (42%) sexually active youth had HIV RNA ≥5000 copies/mL after sexual initiation. Viral drug resistance testing, available for 37 of these 39 youth, identified resistance to nucleoside reverse transcriptase inhibitors in 62%, nonnucleoside reverse transcriptase inhibitors in 57%, protease inhibitors in 38%, and all 3 ARV classes in 22%.Conclusions. As PHIV+ youth become sexually active, many engage in behaviors that place their partners at risk for HIV infection, including infection with drug-resistant virus. Effective interventions to facilitate youth adherence, safe sex practices, and disclosure are urgently needed. [ABSTRACT FROM PUBLISHER]

Youth with perinatally acquired human immunodeficiency virus (PHIV+) survive longer with combination antiretroviral therapy, but remain at risk for poor cognitive outcomes. We evaluated whether markers of HIV disease severity relate to default mode resting-state functional connectivity in PHIV+ youth. We conducted resting-state functional neuroimaging and cognitive testing in a subset of 40 PHIV+ youth recruited from a single study site of the Adolescent Master Protocol study conducted by the Pediatric HIV/AIDS Cohort Study (PHACS) network. Current and past HIV disease severity measures (nadir CD4 lymphocyte percentages and peak HIV RNA plasma levels) were obtained from medical charts. We evaluated associations of both HIV disease severity measures and cognitive functioning with between- and within- default mode network (DMN) connectivity using Analysis of Functional NeuroImaging multiple regression analyses, controlling for multiple comparisons. Of the 40 youth, 31 (mean age = 16.5 years) with minimal motion during scans were included. We observed global alterations in DMN within- and between-network connectivity, with significant associations between disease severity and DMN BOLD correlations. Furthermore, patterns of connectivity with the posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC) that varied as a function of peak HIV RNA were found to predict processing speed ability. Alterations in within- and between-network DMN connectivity in PHIV+ youth may reflect global reorganization of the DMN; this could lead to compensatory alterations in both the within- and between-connectivity of large-scale networks, which may ultimately relate to known cognitive processing difficulties in PHIV+ youth.

Introduction: Salivary metabolite profiles are altered in adults with HIV compared to their uninfected counterparts. Less is known about youth with HIV and how oral disorders that commonly accompany HIV infection impact salivary metabolite levels. Objective: As part of the Adolescent Master Protocol multi-site cohort study of the Pediatric HIV/AIDS Cohort Study (PHACS) network we compared the salivary metabolome of youth with perinatally-acquired HIV (PHIV) and youth HIV-exposed, but uninfected (PHEU) and determined whether metabolites differ in PHIV versus PHEU. Methods: We used three complementary targeted and discovery-based liquid chromatography-tandem mass spectrometry (LC–MS/MS) workflows to characterize salivary metabolite levels in 20 PHIV and 20 PHEU youth with and without moderate periodontitis. We examined main effects associated with PHIV and periodontal disease, and the interaction between them. Results: We did not identify differences in salivary metabolite profiles that remained significant under stringent control for both multiple between-group comparisons and multiple metabolites. Levels of cadaverine, a known periodontitis-associated metabolite, were more abundant in individuals with periodontal disease with the difference being more pronounced in PHEU than PHIV. In the discovery-based dataset, we identified a total of 564 endogenous peptides in the metabolite extracts, showing that proteolytic processing and amino acid metabolism are important to consider in the context of HIV infection. Conclusion: The salivary metabolite profiles of PHIV and PHEU youth were overall very similar. Individuals with periodontitis particularly among the PHEU youth had higher levels of cadaverine, suggesting that HIV infection, or its treatment, may influence the metabolism of oral bacteria. [ABSTRACT FROM AUTHOR]

Introduction: Over 265 000 women are living with HIV in the USA, but limited research has investigated the physical, mental and behavioural health outcomes among women living with HIV of reproductive age. Health status during the reproductive years before, during and after pregnancy affects pregnancy outcomes and long-term health. Understanding health outcomes among women living with HIV of reproductive age is of substantial public health importance, regardless of whether they experience pregnancy. The Health Outcomes around Pregnancy and Exposure to HIV/Antiretrovirals (HOPE) study is a prospective observational cohort study designed to investigate physical and mental health outcomes of young women living with HIV as they age, including HIV disease course, engagement in care, reproductive health and choices and cardiometabolic health. We describe the HOPE study design, and characteristics of the first 437 participants enrolled as of 1 January 2024., Methods and Analysis: The HOPE study seeks to enrol and follow 1630 women living with HIV of reproductive age, including those with perinatally-acquired HIV, at 12 clinical sites across 9 US states and Puerto Rico. HOPE studies multilevel dynamic determinants influencing physical, mental and social well-being and behaviours of women living with HIV across the reproductive life course (preconception, pregnancy, post partum, not or never-pregnant), informed by the socioecological model. Key research areas include the clinical course of HIV, relationship of HIV and antiretroviral medications to reproductive health, pregnancy outcomes and comorbidities and the influence of racism and social determinants of health. HOPE began enrolling in April 2022., Ethics and Dissemination: The HOPE study received approval from the Harvard Longwood Campus Institutional Review Board, the single institutional review board of record for all HOPE sites. Results will be disseminated through conference presentations, peer-reviewed journals and lay summaries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Among 234 US youths with perinatal human immunodeficiency virus, 75% had antiretroviral resistance, substantially higher than that of the reference laboratory overall (36%-44%). Resistance to newer antiretrovirals and to all antiretrovirals in a class was uncommon. The only factor independently associated with future resistance was a higher peak viral load., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Two doses of live-attenuated varicella-zoster vaccine are recommended for human immunodeficiency virus 1 (HIV-1)-infected children with CD4% ≥ 15%. We determined the prevalence and persistence of antibody in immunized children with perinatal HIV (PHIV) and their association with number of vaccinations, combination antiretroviral therapy (cART), and HIV status., Methods: The Adolescent Master Protocol is an observational study of children with PHIV and perinatally HIV-exposed but uninfected (PHEU) children conducted at 15 US sites. In a cross-sectional analysis, we tested participants' most recent stored sera for varicella antibody using whole-cell and glycoprotein enzyme-linked immunosorbent assay. Seropositivity predictors were identified using multivariable logistic regression models and C statistics., Results: Samples were available for 432 children with PHIV and 221 PHEU children; 82% of children with PHIV and 97% of PHEU children were seropositive (P < .001). Seropositivity after 1 vaccine dose among children with PHIV and PHEU children was 100% at <3 years (both), 73% and 100% at 3-<7 years (P < .05), and 77% and 97% at ≥ 7 years (P < .01), respectively. Seropositivity among recipients of 2 vaccine doses was >94% at all intervals. Independent predictors of seropositivity among children with PHIV were receipt of 2 vaccine doses, receipt of 1 dose while on ≥ 3 months of cART, compared with none (adjusted odds ratio [aOR]: 14.0 and 2.8, respectively; P < .001 for overall dose effect), and in those vaccinated ≥ 3 years previously, duration of cART (aOR: 1.29 per year increase, P = .02)., Conclusions: Humoral immune responses to varicella vaccine are best achieved when children with PHIV receive their first dose ≥ 3 months after cART initiation and maintained by completion of the 2-dose series and long-term cART use., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)