Strengthening the evidence to improve health outcomes of children with perinatal HIV exposure.

INTRODUCTION: The number of children exposed to HIV and possibly to antiretroviral therapy (ART) in utero and during breastfeeding and are uninfected (HEU) globally will continue to increase from the estimated 15.9 million in 2021. DISCUSSION: There are still significant gaps in our understanding of the impact of HIV and/or ART exposure in children who are HEU, in terms of prevalence/incidence and severity on health and wellbeing, and long after exposure has ended. While there have been substantial programmatic efforts to support the elimination of vertical transmission of HIV, additional rigorous research is needed to better understand the biological, (psycho)social and structural factors contributing to optimal health for populations who are HEU. Furthermore, the best approaches to address and study the gaps in understanding also need to be explored. Given the scope of the problem including the large numbers of affected people as well as the often limited and competing in-country resources for populations affected by HIV, novel methodologies, including multi-level approaches and advanced analytics, need to be considered. CONCLUSIONS: A growing population of children who are HEU are maturing into adolescence and young adulthood. Research to advance understanding of the possible negative long-term effects of HIV and/or ART exposure in these youth is supported by the US National Institutes of Health. Both large epidemiological studies and smaller more comprehensive cohort studies may be required to address the complexity of the issue. Integrating both types of studies could allow the establishment of more reliable and validated predictions of which youth who are HEU are at the highest risk for specific negative health outcomes, such as mental health and neurocognitive disorders, and which interventional approaches may be most successful to address specific deficits both in terms of prevention and treatment. Finally, these goals can be more rapidly achieved with data science efforts, data harmonisation between studies and with sustainable data-sharing practices. It is important to expand the commitment to research to identify biological, social and structural drivers, to develop screening tools, and impactful and contextually appropriate interventions to address the health and wellbeing of children who are HEU from birth through adulthood.

Adolescent and young adult research across the HIV prevention and care continua: an international programme analysis and targeted review.

INTRODUCTION: Human immunodeficiency virus (HIV) continues to rise in young people among low- and middle-income countries (LMIC). The US National Institutes of Health (NIH) supports the largest public investment in HIV research globally. Despite advancements in the last decade, adolescents and young adults (AYA) remain underrepresented in research to improve HIV prevention and care. We undertook a programme analysis of NIH grants and conducted a targeted review of linked publications on international AYA research across the HIV prevention and care continuum (HPCC) to inform new initiatives to address the needs of AYA in these settings. METHODS: NIH-funded grants from 2012 to 2017, pertaining to AYA in LMIC, and evaluating areas of HIV prevention, care and/or treatment were identified. A systematic review of publications limited to funded grants was performed in two waves: 2012-2017 and 2018-2021. The review included a landscape assessment and an evaluation of NIH-defined clinical trials, respectively. Data on outcomes across the HPCC were abstracted and analysed. RESULTS: Among grant applications, 14% were funded and linked to 103 publications for the analytic database, 76 and 27 from the first and second waves, respectively. Fifteen (15%) wave 1 and 27 (26%) wave 2 publications included an NIH-defined clinical trial. Among these, 36 (86%) did not target a key population (men who have sex with men, drug users and sex workers) and 37 (88%) were exclusively focused on sub-Saharan Africa. Thirty (71%) publications addressed at least one HPCC milestone. Specific focus was on milestones in HIV prevention, care or both, for 12 (29%), 13 (31%) and five (12%) of publications, respectively. However, few addressed access to and retention in HIV care (4 [14%]) and none included microbicides or treatment as prevention. More focus is needed in crucial early steps of the HIV care continuum and on biomedical HIV prevention interventions. DISCUSSION AND CONCLUSIONS: Research gaps remain in this portfolio across the AYA HPCC. To address these, NIH launched an initiative entitled Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource Constrained Settings (PATC3 H) to generate needed scientific innovation for effective public health interventions for AYA affected by HIV in LMIC.

Fostering successful and sustainable collaborations to advance implementation science: the adolescent HIV prevention and treatment implementation science alliance.

INTRODUCTION: HIV continues to devastate the adolescent population in sub-Saharan Africa (SSA). The complex array of interpersonal, social, structural and system-level obstacles specific to adolescents have slowed progress in prevention and treatment of HIV in this population. The field of implementation science holds promise for addressing these challenges. DISCUSSION: There is growing consensus that enhanced interactions between researchers and users of scientific evidence are important and necessary to tackle enduring barriers to implementation. In 2017, the Fogarty International Center launched the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) to promote communication and catalyse collaboration among implementation scientists and implementers to enhance the cross-fertilization of insights as research advances and the implementation environment evolves. This network has identified key implementation science questions for adolescent HIV, assessed how members' research is addressing them, and is currently conducting a concept mapping exercise to more systematically identify implementation research priorities. In addition, AHSA pinpointed common challenges to addressing these questions and discussed their collective capacity to conduct implementation science using the shared learning approach of the network. Specifically, AHISA addresses challenges related to capacity building, developing mentorship, engaging stakeholders, and involving adolescents through support for training efforts and funding region-/country-specific networks that respond to local issues and increase implementation science capacity across SSA. CONCLUSIONS: Innovative platforms, like AHISA, that foster collaborations between implementation science researchers, policymakers and community participants to prioritizes research needs and identify and address implementation challenges can speed the translation of effective HIV interventions to benefit adolescent health.

Healthcare Transition Outcomes Among Young Adults With Perinatally Acquired Human Immunodeficiency Virus Infection in the United States.

BACKGROUND: Young adults with perinatally acquired HIV (YPHIVs) living in the United States are transitioning to adult clinical care, yet there is little information on factors that affect transition outcomes. METHODS: YPHIVs aged ≥18 years in the Pediatric HIV/AIDS Cohort Study (PHACS) AMP Up cohort approaching or having completed transition from pediatric to adult healthcare were included. Demographic and clinical characteristics and self-reported ability to self-manage healthcare were compared by transition status, and multivariable logistic regression models examined factors associated with satisfaction with, and retention in, adult clinical care (clinic visit within the previous 6 months). RESULTS: Most of the 455 YPHIVs, regardless of transition status, reported satisfaction with their clinic and care provider, but many reported antiretroviral medication nonadherence. Of the 124 YPHIVs who had transitioned, 56% had periods of unsuppressed HIV-1 RNA in the year before transition. Those who had transitioned were more likely to report high ability to self-manage their healthcare (ability to manage ≥7 of 8 skills) than those not transitioned. High self-management was associated with retention after transition (odds ratio, 3.40; 95% confidence interval, 1.33-9.12). Higher perceived emotional social support was also associated with retention. Older age at transition was associated with greater satisfaction with provider and clinic. CONCLUSIONS: YPHIVs have positive associations with their clinical care around the time of their transition to adult care, but unsuppressed viral load and suboptimal adherence are a concern. Strengthening skills that increase ability to self-manage care and enhance social support may increase retention in care and improve clinical health.

Nonadherence and unsuppressed viral load across adolescence among US youth with perinatally acquired HIV.

OBJECTIVE: To identify factors associated with nonadherence and unsuppressed viral load across adolescence among youth with perinatally acquired HIV. DESIGN: Longitudinal study at 15 US clinical sites. METHODS: Self-reported antiretroviral medication nonadherence (any missed dose, past week) and unsuppressed viral load (HIV RNA > 400 copies/ml) were assessed annually. Individual, caregiver, social, and structural factors associated with nonadherence and unsuppressed viral load were identified by age (years): 8-11 (preadolescence), 12-14 (early adolescence), 15-17 (middle adolescence), and 18-22 (late adolescence/young adulthood), utilizing multivariable generalized linear mixed effects models. RESULTS: During a median 3.3-year follow-up, 381 youth with perinatally acquired HIV contributed viral load measurements and 379 completed 1190 adherence evaluations. From preadolescence to late adolescence/young adulthood, prevalence of nonadherence increased from 31 to 50% (P < 0.001); prevalence of unsuppressed viral load increased from 16 to 40% (P < 0.001). In adjusted analyses, in pre, middle, and late adolescence/young adulthood, perceived antiretroviral side effects were associated with nonadherence. Additional factors associated with nonadherence included: in preadolescence, using a buddy system (as an adherence reminder); in early adolescence, identifying as black, using buddy system; in middle adolescence, CD4% less than 15%, unmarried caregiver, indirect exposure to violence, stigma/fear of inadvertent disclosure, stressful life events. Associations with unsuppressed viral load included: in early adolescence, youth unawareness of HIV status, lower income; in middle adolescence, perceived antiretroviral side effects, lower income; in late adolescence/young adulthood, distressing physical symptoms, and perceived antiretroviral side effects. CONCLUSION: Prevalence of nonadherence and unsuppressed viral load increased with age. Associated factors varied across adolescence. Recognition of age-specific factors is important when considering strategies to support adherence.

Improving the Youth HIV Prevention and Care Continuums: The Adolescent Medicine Trials Network for HIV/AIDS Interventions.

BACKGROUND: Epidemiologic and clinical information in the United States indicate that HIV transmission and acquisition among adolescents and young adults (youth) remain unchanged, without improvement. Interventions to prevent HIV transmission among youth are critically needed, as are interventions to improve adherence to all components of the continuum of care for youth living with HIV. OBJECTIVE: The primary mission of the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) is to conduct both independent and collaborative research that explores promising behavioral, microbicidal, prophylactic, therapeutic, and vaccine modalities in HIV-infected and at-risk youth aged between 12 and 24. METHODS: Through the ATN, the National Institutes of Health is supporting HIV interventional research for youth in the United States. RESULTS: The ATN comprises 3 cooperative multiproject research programs and a coordinating center. Each program is led by a network hub and has well-defined research themes to assist, guide, and coordinate HIV research project activities. CONCLUSIONS: ATN activities encompass the full spectrum of research needs for youth, from HIV primary prevention for at-risk youth in the community to secondary and tertiary prevention with clinical management of HIV infection among youth living with HIV experiencing adherence challenges.

Roles of Medication Responsibility, Executive and Adaptive Functioning in Adherence for Children and Adolescents With Perinatally Acquired HIV.

BACKGROUND: Medication adherence is a critical but challenging developmental task for children and adolescents with perinatally acquired HIV (PHIV). Understanding how medication responsibility, executive functions (EFs) and adaptive functioning (AF) influence adherence may help prepare adolescents for transition to adulthood. METHODS: Participants included PHIV children and adolescents 7-16 years of age enrolled in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, who were prescribed antiretroviral medications. Measures included caregiver report and child self-report measures of adherence, medication responsibility and EF, caregiver report of child AF, examiner-administered tests of EF and processing speed and demographic and health characteristics. RESULTS: Two hundred fifty-six participants with PHIV (mean age: 12 years old) were 51% female, 80% black and 79% non-Hispanic. Per 7-day recall, 72% were adherent (no missed doses). Children/adolescents self-reported that 22% had sole and 55% had shared medication responsibility. Adjusted logistic models revealed significantly higher odds of adherence with sole caregiver responsibility for medication [odds ratio (OR): 4.10, confidence interval (CI): 1.43-11.8, P = 0.009], child nadir CD4% <15% (OR: 2.26, CI: 1.15-4.43, P = 0.018), better self-reported behavioral regulation (OR: 0.65, CI: 0.44-0.96, P = 0.029) and slower processing speed (OR: 0.54, CI: 0.38-0.77, P < 0.001), adjusting for demographic variables (age, race and caregiver education). CONCLUSIONS: Among children and adolescents with PHIV, continued caregiver medication management, especially during adolescence, is essential. Although global EF and AF were not significantly associated with adherence, behavioral regulation was. Given that EF and AF develop throughout adolescence, their relationships to adherence should be evaluated longitudinally, especially as youth transition to adulthood and caregiver responsibility diminishes.

Following young people with perinatal HIV infection from adolescence into adulthood: the protocol for PHACS AMP Up, a prospective cohort study.

INTRODUCTION: The first generation of adolescents born with HIV infection has reached young adulthood due to advances in treatment. It is important to continue follow-up of these individuals to assess their long-term medical, behavioural and mental health and ability to successfully transition to adulthood while coping with a chronic, potentially stigmatising condition. To accomplish this, and to maintain their interest in long-term research participation, we need to accommodate the changing lifestyles and interests of young adult study participants while ensuring valid data collection. We report the protocol for Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) Up, a prospective cohort study enrolling young adult participants for long-term follow-up. METHODS AND ANALYSIS: AMP Up is recruiting 850 young men and women 18 years of age and older-600 perinatally HIV-infected and a comparison group of 250 perinatally HIV-exposed, uninfected-at 14 clinical research sites in the USA and Puerto Rico. Recruitment began in April 2014 and is ongoing, with 305 participants currently enrolled. Planned follow-up is ≥6 years. Data are collected with a flexible hybrid of online and in-person methods. Outcomes include: transition to adult clinical care and retention in care; end-organ diseases; malignancies; metabolic complications; sexually transmitted infections; reproductive health; mental health and neurocognitive functioning; adherence to antiretroviral treatment; sexual behaviour and substance use; hearing and language impairments; and employment and educational achievement. ETHICS AND DISSEMINATION: The study received ethical approval from the Harvard T.H. Chan School of Public Health's institutional review board (IRB), and from the IRBs of each clinical research site. All participants provide written informed consent; for cognitively impaired individuals with legally authorised representatives, legal guardian permission and participant assent is obtained. Findings will be disseminated through peer-reviewed journals, conference presentations and participant summaries.

National Institutes of Health investment in studies of HIV disclosure to children.

The goals of this manuscript will be to review current and past National Institutes of Health (NIH) funding on maternal and child HIV disclosure research and lay out current research gaps in these areas. Examples of work funded by NIH will highlight how the disclosure needs of families affected by HIV have changed over the past 30 years as well as highlight what we have learned. The review will include the recent NICHD RFA that focused specifically on disclosure of HIV status to children in low and middle-income country settings. A brief description of findings from these NIH-funded grants will be provided. The authors will then describe current research gaps and challenges as they relate to research on HIV disclosure both in the U.S. and internationally.

Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load (<400 copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p = 0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio = 4.1, 95% confidence interval: 1.8-9.1; p < 0.001), but not at enrollment or the 6-month visit (p > 0.3). Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p < 0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p ≤ 0.005), but not at the 6-month visit (p = 0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population.

Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America.

Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load (<400 copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p=0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio=4.1, 95% confidence interval: 1.8-9.1; p<0.001), but not at enrollment or the 6-month visit (p>0.3). Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p<0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤0.005), but not at the 6-month visit (p=0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population.

Innovative uses of communication technology for HIV programming for men who have sex with men and transgender persons.

Globally, overall rates of HIV are on the decline; however, rates among gay men and other men who have sex with men (MSM) and transgender persons are increasing. Meanwhile, there has been exponential growth in access to communication technology over the last decade. More innovative prevention and care technology-based programmes are needed to help address the growing numbers of MSM and transgender persons living with HIV and those at risk for infection. To address this need, a meeting was hosted by the U.S. Agency for International Development (USAID) through the President's Emergency Plan for AIDS Relief (PEPFAR) and co-sponsored by amfAR, The Foundation for AIDS Research and the National Institute of Mental Health (NIMH). The meeting brought together researchers, community implementers, advocates and federal partners to discuss the current landscape of technology-based interventions for MSM and transgender persons and to discuss key considerations. Presentations and discussions focused on the research gaps, facilitators and barriers to programme implementation and public-private partnerships. This article summarizes the meeting proceedings and outlines key considerations for future work in this area.

Prevalence, incidence, and persistence of psychiatric and substance use disorders among mothers living with HIV.

OBJECTIVE: To evaluate prevalence, incidence, remission, and persistence of psychiatric and substance use disorders among HIV-infected mothers and identify biopsychosocial correlates. METHODS: HIV-infected mothers (n = 1223) of HIV-exposed uninfected children enrolled in a prospective cohort study; HIV-uninfected mothers (n = 128) served as a comparison group. Mothers provided sociodemographic and health information and completed the Client Diagnostic Questionnaire (CDQ). Prevalence of any psychiatric or substance use disorder at initial evaluation was compared between the 2 groups. Incident, remitting, and persisting disorders were identified for 689 mothers with HIV who completed follow-up CDQs. We used logistic regression to evaluate adjusted associations of biopsychosocial characteristics with presence, incidence, remission, and persistence of disorders. RESULTS: Thirty-five percent of mothers screened positive for any psychiatric or substance use disorder at initial evaluation, with no difference by maternal HIV status (P = 1.00). Among HIV-infected mothers, presence of any disorder was associated with younger age [adjusted odds ratio (aOR): 1.39; 95% CI: 1.09 to 1.75], single parenthood (aOR: 1.35; 95% CI: 1.08 to 1.68), and functional limitations (aOR: 2.29; 95% CI: 1.81 to 2.90). Incident disorders were associated with functional limitations (aOR: 1.92; 95% CI: 1.10 to 3.30). Among HIV-infected mothers with a disorder at initial evaluation (n = 238), 61% had persistent disorders. Persistent disorders were associated with lower income (aOR: 2.44; 95% CI: 1.33 to 4.76) and functional limitations (aOR: 3.19; 95% CI: 1.87 to 5.48). Receipt of treatment for any disorder was limited: 4.5% at study entry, 7% at follow-up, 5.5% at both entry and follow-up. CONCLUSIONS: Psychiatric and substance use disorders remain significant comorbid conditions among HIV-infected mothers and require accessible evidence-informed treatment.

Relationship between viral load and self-report measures of medication adherence among youth with perinatal HIV infection.

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.

Evaluation of risk for late language emergence after in utero antiretroviral drug exposure in HIV-exposed uninfected infants.

BACKGROUND: Combination antiretroviral (cARV) regimens are recommended for pregnant women with HIV to prevent perinatal HIV transmission. Safety is a concern for infants who were HIV-exposed but uninfected, particularly for neurodevelopmental problems, such as language delays. METHODS: We studied late language emergence (LLE) in HIV-exposed but uninfected children enrolled in a US-based prospective cohort study. LLE was defined as a caregiver-reported score ≤10th percentile in any of 4 domains of the MacArthur-Bates Communicative Development Inventory for 1-year olds and as ≥1 standard deviation below age-specific norms for the Ages and Stages Questionnaire for 2-year olds. Logistic regression models were used to evaluate associations of in utero cARV exposure with LLE, adjusting for infant, maternal and environmental characteristics. RESULTS: 1129 language assessments were conducted among 792 1- and 2-year-old children (50% male, 62% black and 37% Hispanic). Overall, 86% had in utero exposure to cARV and 83% to protease inhibitors. LLE was identified in 26% of 1-year olds and 23% of 2-year olds, with higher rates among boys. In adjusted models, LLE was not associated with maternal cARV or ARV drug classes in either age group. Among cARV-exposed 1-year olds, increased odds of LLE was observed for those exposed to atazanavir (adjusted odds ratio = 1.83, 95% confidence interval: 1.10-3.04), particularly after the first trimester (adjusted odds ratio = 3.56, P = 0.001), compared with atazanavir-unexposed infants. No associations of individual ARV drugs with LLE were observed among 2-year olds. CONCLUSIONS: In utero cARV exposure showed little association with LLE, except for a higher risk of language delay observed in 1-year-old infants with atazanavir exposure.

Preventing HIV among young people: research priorities for the future.

OBJECTIVE: To review the current state of knowledge on the prevention of sexual transmission of HIV in adolescents and to highlight the existing gaps and priority areas for future research. BACKGROUND: A disproportionate burden of HIV infections falls on adolescents, a developmental stage marked by unique neural, biological, and social transition. Successful interventions are critical to prevent the spread of HIV in this vulnerable population. METHODS: We summarized the current state of research on HIV prevention in adolescents by providing examples of successful interventions and best practices, and highlighting current research gaps. RESULTS: Adolescent interventions fall into 3 main categories: biomedical, behavioral, and structural. The majority of current research has focused on individual behavior change, whereas promising biomedical and structural interventions have been largely understudied in adolescents. Combination prevention interventions may be particularly valuable to this group. CONCLUSIONS: Adolescents have unique needs with respect to HIV prevention, and, thus, interventions should be designed to most effectively reach out to this population with information and services that will be relevant to them.

A meta-analysis of adherence to antiretroviral therapy and virologic responses in HIV-infected children, adolescents, and young adults.

The relationship between adherence to antiretroviral therapy (ART) and virologic outcomes in HIV+ children, adolescents, and young adults has been notably understudied, with much of the extant research focused on specific sub-literatures, such as resource-limited regions, specific clinical outcomes and time frames. The authors sought to better characterize the relationship between adherence to ART and virologic functioning along various sample and methodological factors. The authors conducted a meta-analysis of thirty-seven studies and utilized a random effects model to generate weighted mean effect sizes. In addition, the authors conducted meta-ANOVAs to examine potential factors influencing the relationship between adherence and three categories of clinical outcomes, specifically Viral Load (VL) <100, VL < 400, and continuously measured VL. The analyses included 5,344 HIV+ children, adolescents, and young adults. The relationship between adherence behaviors and virologic outcomes varied across different methods of measurement and analysis. The relationship between adherence and continuously measured VL was significantly larger than for dichotomously-coded VL < 400 at Qb (20.69(1), p < .0005). Caregiver self-report indices elicited very small to small magnitude effects across both VL < 100 and VL < 400 outcomes and combined informant reporting (youth/adolescent and parent) produced significantly larger effects than caregiver report alone with adherence and VL < 400 outcomes at Qb (9.28(1), p < .005). More recently published trials reported smaller relationships between adherence and categorical clinical outcomes, such that year of publication significantly negatively correlated with VL < 100 (r = -.71(14), p < .005) and VL < 400 (r = -.43(26), p < .02). The data suggest that the magnitude of the relationship between ART adherence and virologic outcomes among heterogeneous samples of HIV+ children, adolescents and young adults varies across virologic outcomes and may be affected by moderating sample and methodological factors. Methodological and research recommendations for the interpretation of the current findings as well as for future HIV adherence related research are presented.

Sexual risk behavior among youth with perinatal HIV infection in the United States: predictors and implications for intervention development.

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.