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

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EPIDEMIOLOGY AND SOCIAL

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

Kacanek, Deboraha,b; Huo, Yanlinga,b; Malee, Kathleenc; Mellins, Claude A.d; Smith, Reneee; Garvie, Patricia A.f; Tassiopoulos, Katherineg; Lee, Soniah; Berman, Claire A.g; Paul, Maryi; Puga, Anaf; Allison, Susannahj for the Pediatric HIV/AIDS Cohort Study

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AIDS 33(12):p 1923-1934, October 1, 2019. | DOI: 10.1097/QAD.0000000000002301

Abstract

Introduction

Globally, ∼1.8 million adolescents live with HIV [1]. In the United States, in 2016, ∼12 000 children, adolescents, and young adults were living with perinatally acquired HIV (PHIV), of whom 1814 were under the age of 13 and 10 101 were adolescents and young adults [2]. Among children, adolescents, and young adults with PHIV infection, achieving and maintaining adherence to antiretroviral therapy (ART) is challenging yet essential for viral suppression, prevention of resistant HIV strains [3–5], and reduced HIV transmission risk [6]. Adherence is especially complex during adolescence, a dynamic period of physical, cognitive, social, and emotional changes that encompass increasing independence, experimentation, and identity development [7–9]. Across chronic health conditions, adolescents may be more adherent during some periods than others; thus, factors that affect adherence during early adolescence may be different than during late adolescence/young adulthood [9,10]. Multiple factors contribute to ART adherence throughout childhood and adolescence, including individual [11–15], family [11,16,17], social [11], and structural characteristics [12,18–20] that may shift over time.

Suboptimal ART adherence and loss of virologic suppression are more frequent among adolescents than younger children [11,14,16,21–23] and adults [24,25]. However, little is known about whether factors associated with adherence vary at different stages of adolescence. Age ranges across studies vary, with few results disaggregated by age.

To intervene effectively at all stages of adolescence and young adulthood, longitudinal studies are needed to identify factors associated with adherence as youth age. This longitudinal study sought to determine the prevalence of nonadherence to ART and unsuppressed viral load as youth with PHIV age; and identify individual, family, social, and structural factors associated with nonadherence and unsuppressed viral load across stages of adolescence. We considered adherence in the context of developmental changes of adolescence and young adulthood [9]. Social ecological models of health behavior [26], which recognize the social and environmental context in which health behavior occurs, informed our approach. We hypothesized that family-level factors would be associated with nonadherence in pre and early adolescence, and that social and structural factors would be associated with nonadherence during middle and late adolescence.

Methods

We included children, adolescents, and young adults (ages 8–22, hereafter referenced as ‘youth’) with PHIV enrolled in the Adolescent Master Protocol (AMP) of the Pediatric HIV/AIDS Cohort Study (PHACS), a prospective study of the impact of HIV and ART on youth with PHIV. AMP enrolled children and adolescents with PHIV and their caregivers at 15 US clinical sites, including Puerto Rico, from March 2007 to October 2009. Participants completed follow-up visits every 6 months (2007–2010), then annually (2010–). This analysis used data as of 7/1/2014. Visits include clinical examinations, medical record abstraction, and interviews. Inclusion criteria were: PHIV, age 7–15 years at entry, engaged in medical care, with available medical records. Institutional review boards at all sites and at Harvard T.H. Chan School of Public Health approved the protocol. Parents or legal guardians provided written informed consent; children and adolescents provided assent per local IRB guidelines. Upon turning 18, participating youth provided consent to continue study participation.

Included in this analysis were youth who indicated receipt of ART at enrollment or follow-up and also had at least 1 youth-reported or caregiver-reported adherence evaluation, and/or viral load measurement in the adherence visit window.

Outcome measures

We assessed two ART nonadherence outcomes: first, youth or caregiver-reported nonadherence; and second, unsuppressed viral load. Youths’ ART adherence was assessed annually from the 6 month to 2.5 year visits and from the 4-year visit onward during separate interviews with youth and caregivers using a questionnaire from the Pediatric AIDS Clinical Trials Group [27,28] modified by PHACS. AMP assessed (for each antiretroviral medication prescribed) the number of doses missed in the previous 7 days. Nonadherence was defined as youth or caregiver report of one or more missed ART doses in the past week, associated with unsuppressed viral load in previous work [22]. HIV-RNA data were abstracted from medical records at each visit. The measure obtained closest to and within ±3 months of each self-reported adherence assessment was included. Unsuppressed viral load was defined as HIV-RNA more than 400 copies/ml.

Age strata

Using time-varying age in years, we defined four age strata corresponding to stages of adolescence [29]: preadolescence (8–11 years), early adolescence (12–14 years), middle adolescence (15–17 years), and late adolescence/young adulthood (18–22 years).

Covariates

The most recent individual, family, social, and structural-level covariates measured during each adherence assessment (unless indicated otherwise) were examined.

Individual characteristics included youth's sex, race, ethnicity, and nadir CD4+% at baseline, ART regimen (combination ART defined as three or more drugs), medication burden (single vs. multiple dose regimen), distressing physical symptoms (youth and/or caregiver reports), perceived ART side effects, youth awareness of their HIV status, alcohol use, and emotional and behavioral health. Caregivers and youth were interviewed separately about youth's experience of 20 physical symptoms (e.g., dizziness, chest pain), rating symptom distress over the past 4 weeks. Presence of distressing symptoms was defined as reporting at least one moderately or more distressing physical symptom. Perceived ART side effects were defined as youth or caregiver report that the youth missed taking ART in the past 6 months sometimes or often because they ‘wanted to avoid side effects (feeling sick).’ Youth awareness of their HIV status (reported by caregiver), was defined as whether the youth had been told they had HIV. Youth alcohol use reflected self-reported use in the past 3 months [assessed at ≥10 years of age via audio computer-assisted survey interview (ACASI)]. Emotional problems were assessed with the Behavior Assessment System for Children-Second Edition (BASC-2) youth Self-Report of Personality (SRP) Emotional Symptoms Index (ESI) [30]. Behavioral problems were measured by the BASC-2 caregiver-reported Behavioral Symptoms Index (BSI). For both the ESI and BSI, presence of problems was defined as a score in or exceeding the ‘at risk’ (T ≥ 60) range.

Family characteristics included caregiver's educational attainment, marital status, and living arrangement at baseline, annual household income, number of caregiver health limitations, and youth relationship with caregiver (measured with the BASC-2 Youth SRP Personal Adjustment Composite); presence of problems was defined as a score in the ‘at risk’ or ‘clinically significant’ (T ≤ 40) range.

Social characteristics included whether the youth currently had a boyfriend or girlfriend (assessed via ACASI), youth or caregiver-reported use of a ‘buddy system’ to support adherence, and stigma/concern about inadvertent disclosure of youth's HIV status, defined as youth or caregiver reporting that the youth missed taking ART medication in the past 6 months ‘sometimes’ or ‘often’ because of not wanting others seeing the youth taking medications.

Structural characteristics included exposure to violence between ages 8 and 15, and number of stressful life events. Self-reported exposure to violence was assessed at ages 8–15 as part of the Life Events Checklist (LEC) [31]. The LEC assesses self-reported exposure to stressful life events within the past year and has been used in other studies of children living with or affected by HIV [32]. Seven LEC items pertain to direct and indirect exposure to violence. Indirect exposure to violence was defined as report of at least 1 event in the past year including witnessed a fight with a weapon; heard gunshots on their block; people in the neighborhood were hit by the police; or murdered. Direct violence victimization was defined as report of at least one event in the past year, including having been physically attacked; raped or sexually assaulted; or robbed or burglarized. Any violence exposure was defined as report of either indirect exposure to violence or direct violence victimization. Youth exposure to stressful life events was assessed annually from the 1 to 5-year visit and biennially thereafter through interviews with caregivers and, beginning at age 12, also with youth. Participants were asked about occurrence of 18 events within the past year (e.g., parents separated, loss of health insurance). The number of events reported was summed and categorized (0, 1, 2, ≥3) for caregivers and youth. For adherence visits where a listed variable should have been measured but was not, we considered the data as missing.

Statistical analysis

For both adherence outcomes, we compared baseline characteristics of adherent and nonadherent youth, using chi-square and Fisher's exact tests for categorical variables, and t tests and Wilcoxon rank-sum tests for continuous variables, as appropriate. ‘Baseline’ data for this analysis were data obtained beginning at the 1 and 1.5-year AMP visits since most covariates of interest were assessed beginning at the 1-year visit. Using data from all available follow-up visits, we estimated the prevalence of nonadherence during preadolescence, early adolescence, middle adolescence, and late adolescence/young adulthood. To evaluate associations of each covariate with nonadherence within each age stratum, unadjusted and adjusted generalized linear mixed effects models were fit to account for correlation in repeated longitudinal measures within each participant. Covariates with P value of 0.10 or less in unadjusted analyses were considered for inclusion in multivariable models and retained in a core model if the P value was of 0.10 or less. Final models for each age stratum included core model covariates and covariates with P value of 0.10 or less when added back to the core model. Variables with data missing for at least 25% of participants within an age group were not considered for multivariable models.

Using data from the aggregate (not age-stratified) sample, we evaluated whether the association of each covariate with each outcome varied across developmental stage, by including an interaction between age group and each covariate. Interactions were first evaluated in unadjusted models including the interaction term and main effects of the two variables; when the interaction P value was 0.10 or less, multivariable models were fit adjusting for covariates selected a priori (sex, race, caregiver living arrangement, and household annual income). When the interaction P value was 0.05 or less in the adjusted model, we calculated predicted probabilities of the outcome at each age in those with and without the characteristic of interest. All analyses used SAS 9.4 (SAS Institute Inc., Cary, North Carolina, USA).

Results

Of 451 PHIV youth enrolled, 427 attended at least one protocol visit requiring an adherence evaluation as of 1 July 2014, of whom 426 reported ever receiving ART. Within this group, 410 youth (or caregivers) completed at least one valid adherence evaluation, 381 (1257 measurements) of whom had viral load measurements obtained within 3 months of a scheduled adherence visit occurring after the 1-year follow-up visit and were included in the viral load analysis. A total of 379 of the 410 participants completed at least one adherence assessment after the 1-year follow-up visit, with 1190 total evaluations. Most characteristics of included participants did not differ significantly from those of excluded participants; included participants more frequently received ART before or at enrollment (95 vs. 78%), and had a caregiver living with a partner (51 vs. 32%) compared with excluded participants. Table 1 summarizes baseline characteristics of participating youth by adherence and viral load status. The mean age was 13 years, 53% were female, 74% identified as Black, and 23% identified as Latinx. Thirty percent reported nonadherence, and 29% had unsuppressed viral load (Table 1). At baseline, 36% of nonadherent youth vs. 21% of adherent youth had unsuppressed viral load (P = 0.006) (data not shown in tables).

T1-12
Table 1:
Baseline characteristics by self-reported nonadherence and unsuppressed viral load among youth with perinatally-acquired HIV in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, 2007–2014.

Of 1190 adherence evaluations completed, 14% were during preadolescence, 32% during early adolescence, 36% during middle adolescence, and 17% during late adolescence/young adulthood. The median duration from earliest to most recent included adherence and viral load evaluation was 3.4 years (range: 0–5 years). Thirty percent of participants contributed data to one, 59% to two, and 11% to three age groups. From preadolescence to late adolescence/young adulthood, prevalence of self-reported nonadherence increased from 31 to 50% (P < 0.001) and prevalence of unsuppressed viral load increased from 16 to 40% (P < 0.001) (Fig. 1). The distribution of most covariates did not differ across developmental stages, but the proportion of visits when youth reported alcohol use, having a boyfriend/girlfriend, or being aware of their HIV status increased with age (see Table, Supplemental Digital Content 1, https://links.lww.com/QAD/B500, which describes the distribution of covariates by developmental stage).

F1-12
Fig. 1:
Prevalence of nonadherence and unsuppressed viral load by age in Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol.N = 1190 self-reported and/or caregiver-reported adherence evaluations of 379 youth; N = 1257 viral load measurements from 381 youth. CI, confidence interval; VL, viral load.

Factors associated with nonadherence

Table 2 summarizes multivariable analysis results within each age stratum. Factors associated with nonadherence included: during preadolescence, using a ‘buddy system’ adherence reminder; during early adolescence, identifying as Black, and using a buddy system adherence reminder; during middle adolescence, nadir CD4+% less than 15%, alcohol use, having an unmarried caregiver, indirect exposure to violence, stigma/concern about inadvertent disclosure, and stressful life events. During all but early adolescence, perceived ART side effects were associated with nonadherence, with the greatest magnitude in preadolescence and mid-adolescence (Table 2). Results from univariable analyses within each age stratum are summarized in eTable 2 (see Table, Supplemental Digital Content 2, https://links.lww.com/QAD/B500, which presents unadjusted associations of each covariate with nonadherence within each age stratum).

T2-12
Table 2:
Adjusted associations of covariates with self-reported nonadherence at different age stages (N = 1190 evaluations of 379 youth).

Factors associated with unsuppressed viral load

Table 3 summarizes results from multivariable models of unsuppressed viral load within each age stratum. Higher risk of unsuppressed viral load was associated with: during early adolescence, youth being unaware of their HIV status and lower household income; during middle adolescence, perceived ART side effects and lower household income; and during late adolescence/young adulthood, experiencing distressing symptoms and perceived ART side effects. No statistically significant associations were observed during preadolescence. Unadjusted associations of each covariate with unsuppressed viral load within each age stratum are summarized in eTable 3 (see Table, Supplemental Digital Content 3, https://links.lww.com/QAD/B500, which presents unadjusted associations of each covariate with unsuppressed viral load within each age stratum).

T3-12
Table 3:
Adjusted associations of covariates with unsuppressed viral load at different age stages (N = 1257 measurements from 381 youth).

The association of violence exposure with self-reported nonadherence was modified by age group, with stronger associations during middle adolescence compared with other developmental stages (Fig. 2). Youth who reported violence exposure had an elevated risk of nonadherence during early adolescence [adjusted odds ratio (aOR) 2.10, 95% confidence interval (CI) 1.17–3.77] and middle adolescence [aOR 3.57, 95% CI 2.02–6.34], but not in preadolescence or late adolescence/young adulthood (interaction P = 0.02).

F2-12
Fig. 2:
Adjusted predicted probabilities (with 95% confidence intervals) of self-reported nonadherence among youth with vs. without exposure to violence in Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol.Model adjusted for sex, race, caregiver living arrangement, and household annual income. P value was for testing the interaction between witnessed or experienced violence and age at self-reported nonadherence evaluation from the adjusted models. Predicted probabilities were among black males who lived in a household with annual income more than $10 000–40 000 and whose caregiver was living with a partner. The data table under the plot presents the number of participants with a specific characteristic and the number (%) with nonadherence (by self or caregiver report) among participants with the specific characteristic, within each group from unadjusted analysis.

There were observed interactions of Black race, Latinx ethnicity, unmarried caregiver, and perceived ART side effects with age group on unsuppressed viral load in unadjusted models. However, associations were not statistically significant in adjusted models (data not shown).

Discussion

In this cohort of youth with PHIV, the prevalence of nonadherence and unsuppressed viral load increased through adolescence and into young adulthood. Individual, family, social and structural factors contributed to nonadherence and unsuppressed viral load, yet associations varied by developmental stage and outcome. As hypothesized, associations of structural factors with nonadherence were stronger in middle adolescence than in other periods. However, we also observed that multiple family factors were associated with nonadherence or unsuppressed viral load during middle adolescence, highlighting the ongoing role of family resources. Although the pattern of increasing nonadherence with age is consistent with prior studies [13,22–24], this study illuminates targets for adherence interventions tailored to stages of adolescent development and unique youth, family, and community strengths and challenges.

In pre and early adolescence, youth who used a ‘buddy system’ reported worse adherence, contrasting with previous studies [11,33]. It could be that this adherence aid was a marker for past or current adherence challenges. We did not distinguish the nature or quality of the relationship of the person providing adherence support. Adolescents ages 12–14 who often desire greater autonomy, may not view caregivers’ adherence reminders as desirable. Yang et al.[34] identified a ‘mismatch between desired and received support’ as an adherence barrier among adolescents living with PHIV in Botswana. In addition, during early adolescence, youth in our study who knew their HIV status were more likely to have suppressed viral load. The WHO recommends that children be disclosed their HIV status by 10–12 years old, yet in our study, 10% of study visits between ages 12 and 14 were among youth who were unaware of their HIV status. US guidelines do not recommend an age by which children should be disclosed their HIV status, and note that timing of disclosure should ‘be based on a comprehensive assessment of the psychosocial milieu and the needs of the child and family,’[35] including consideration of significant cognitive and/or emotional–behavioral difficulties, if present. Counseling caregivers to disclose children's HIV status before early adolescence, if feasible, and addressing caregiver concerns about consequences of disclosure and HIV-related stigma for their children's emotional health and safety, may optimize virologic outcomes once youth reach adolescence [36,37].

In middle adolescence, multiple social and structural factors were associated with nonadherence. As peer relationships and the desire for social acceptance increase in importance [38,39], mid-adolescents’ growing awareness of societal expectations and norms may contribute to behavior that is inconsistent with health demands, such as ART nonadherence. HIV-related stigma, including fears about risk of inadvertent disclosure of HIV status, may eclipse health needs, contribute to feeling socially isolated, and reduce the salience of adherence as a goal, increasing the potential for virologic failure. In addition, we found that exposure to community violence during mid-adolescence elevated risk of nonadherence, extending previous findings [20,40]. Many youth living with HIV and their families experience family and community violence [41], which may compromise youths’ ability to manage normal developmental challenges, alter neurocognitive functioning [42], increase risk for mental health problems [43,44], and be associated with family disruption [41], all of which in turn may contribute to nonadherence. Violence could also be a marker for multiple family and community environmental stressors. During mid-adolescence, opportunities for youths’ independent activity and risk-taking in community environments may increase, which may account for the stronger associations we observed during this period. We also observed that during early and mid-adolescence, youth living in households with low incomes had greater odds of unsuppressed viral load, which could be due to food insecurity [45], insufficient resources to access quality care, or poverty-related stigma and psychosocial stress [46]. In addition, as alcohol use during middle adolescence was associated with nonadherence, addressing risks to nonadherence in the context of alcohol and other substance use is important.

Adherence support for youth during middle adolescence must address potent social environmental risk factors. To diminish risks associated with nonadherence during middle adolescence, integrated services must include screening for violence exposure, and support to youth and their families who have experienced violence, economic hardship, and other adversities. Further, communication with youth about strategies to minimize the risk of and manage an inadvertent disclosure should be implemented early to prepare youth and families with strategies before this stage. Interventions that address economic and social inequity, including Suubi + Adherence [47], which has shown positive effects of economic empowerment on viral suppression among Ugandan HIV+ adolescents, and CHAMP+/VUKA [48–50], a family strengthening intervention which teaches and supports communication and problem-solving strategies for youth living with HIV infection and their families prior to high-risk time periods are critically important. Such interventions might catalyze communication between youth, families, peers, and community stakeholders to share strategies to prevent or buffer the effects of direct and indirect exposure to violence to maintain adherence, and implement them through parental engagement, strengthened social networks, and community supports for youth.

Across multiple developmental stages, the presence of side effects was associated with nonadherence and unsuppressed viral load, consistent with previous studies [51,52]. Associations of side effects and distressing physical symptoms with both outcomes could be due to PHIV youths’ long history of ART medication use, history of exposure to multiple regimens, leading to treatment fatigue [53], and/or to body composition changes that may carry stigma or lead to unwanted questions [54]. During middle and later adolescence/young adulthood, when youth seek peer acceptance and intimate relationships, and have concerns about physical appearance, interventions to support youth experiencing pronounced side effects should assess youths’ concerns about side effects, and how to manage them, through education, treatment, or switching the ART regimen.

The current study has some limitations. The small sample size in some age strata limited statistical power to evaluate associations. Given that this is a clinic-based sample, results may not generalize to all youth with PHIV. Although self-reported adherence was correlated with viral suppression, adherence was assessed infrequently, limiting our ability to capture short-term fluctuations. A strength of this study is that it examined both adherence and viral load longitudinally for a large sample of youth from childhood to early adulthood, with repeated assessments spanning up to 5 years, in contrast to previous studies with shorter observation periods [13,23].

Results of this study have implications for programs and policies to mitigate risk of nonadherence and unsuppressed viral load among youth with PHIV as they transition through adolescence into adulthood: Services to help adolescents with PHIV navigate typical developmental challenges should recognize age-specific risks and build on sources of resilience at individual, family, social, and structural levels. This involves creation and maintenance of a multisystemic alliance that is respectful of unique and evolving characteristics of the child/adolescent within a dynamic family and social context, recognizing the youth's growing autonomy. At the same time, addressing social and structural factors associated with nonadherence, including stigma, violence and poverty, requires societal and policy changes and community advocacy to prevent their occurrence, and resulting health inequities. Future research should evaluate whether findings from this US study generalize to global settings, home to the majority of children and adolescents living with HIV. Intervention research is also urgently needed to reduce age disparities across adolescence in attainment of the UNAIDS 90–90–90 goals, and sustaining virologic suppression, through development and testing of multilevel, multisectoral adherence interventions which build on lessons from studies of children and adults [55,56], across all stages of adolescence.

Acknowledgements

We thank the children and families for their participation in PHACS, and the individuals and institutions involved in the conduct of PHACS. The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Institute of Dental and Craniofacial Research, National Cancer Institute, the National Institute on Alcohol Abuse and Alcoholism, and the National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) (Principal Investigator: George Seage; Program Director: Liz Salomon) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Ellen Chadwick; Project Director: Patrick Davis). Data management services were provided by Frontier Science and Technology Research Foundation (PI: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (PI: Julie Davidson).

The following institutions, clinical site investigators and staff participated in conducting PHACS AMP and AMP Up in 2018, in alphabetical order: Ann & Robert H. Lurie Children's Hospital of Chicago: Ellen Chadwick, Margaret Ann Sanders, Kathleen Malee, Yoonsun Pyun; Baylor College of Medicine: William Shearer, Mary Paul, Norma Cooper, Chivon McMullen-Jackson, Mandi Speer, Lynette Harris; Bronx Lebanon Hospital Center: Murli Purswani, Mahboobullah Mirza Baig, Alma Villegas; Children's Diagnostic & Treatment Center: Lisa Gaye-Robinson Sandra Navarro, Patricia A. Garvie; Boston Children's Hospital: Sandra K. Burchett, Michelle E. Anderson, Adam R. Cassidy; Jacobi Medical Center: Andrew Wiznia, Marlene Burey, Ray Shaw, Raphaelle Auguste; Rutgers - New Jersey Medical School: Arry Dieudonne, Linda Bettica, Juliette Johnson, Karen Surowiec; St. Christopher's Hospital for Children: Janet S. Chen, Maria Garcia Bulkley, Taesha White, Mitzie Grant; St. Jude Children's Research Hospital: Katherine Knapp, Kim Allison, Megan Wilkins, Jamie Russell-Bell; San Juan Hospital/Department of Pediatrics: Midnela Acevedo-Flores, Heida Rios, Vivian Olivera; Tulane University School of Medicine: Margarita Silio, Medea Gabriel, Patricia Sirois; University of California, San Diego: Stephen A. Spector, Megan Loughran, Veronica Figueroa, Sharon Nichols; University of Colorado Denver Health Sciences Center: Elizabeth McFarland, Emily Barr, Carrie Chambers, Mary Glidden; University of Miami: Gwendolyn Scott, Grace Alvarez, Juan Caffroni, Anai Cuadra.

Note: The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the National Institutes of Health or US Department of Health and Human Services.

The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) with co-funding from the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Deafness and Other Communication Disorders (NIDCD), Office of AIDS Research (OAR), the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the National Heart Lung and Blood Institute (NHLBI), through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) and the Tulane University School of Medicine (HD052104).

Author contributions: All authors contributed substantively to this article in the following ways: design (D.K. and S.A.), data analysis (Y.H. and D.K.), acquisition of data and interpretation of results (all authors), drafting the article (D.K. and Y.H.), critical revision of the article (all authors), and final approval of submitted version (all authors).

Conflicts of interest

There are no conflicts of interest.

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Keywords:

adolescent development; medication adherence; social determinants of health; violence; viral load; young adult; youth

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