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.

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.

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.

Language impairment in children perinatally infected with HIV compared to children who were HIV-exposed and uninfected.

OBJECTIVE: To investigate the risk for language impairment (LI) in children perinatally infected or exposed to HIV. METHODS: We evaluated the prevalence of LI in 7- to 16-year-old children with perinatal HIV infection (HIV+) compared with HIV-exposed and uninfected children, using a comprehensive standardized language test (Clinical Evaluation of Language Functioning-Fourth Edition [CELF-4]). LI was classified as primary LI (Pri-LI) (monolingual English exposure and no cognitive or hearing impairment), concurrent LI (Con-LI) (cognitive or hearing impairment), or no LI. Associations of demographic, caregiver, HIV disease, and antiretroviral treatment factors with LI category were evaluated using univariate and multivariable logistic regression models. RESULTS: Of the 468 children with language assessments, 184 (39%) had LI. No difference was observed by HIV infection status for overall LI or for Pri-LI or Con-LI; mean (SD) CELF-4 scores were 88.5 (18.4) for HIV+ versus 87.5 (17.9) for HIV-exposed and uninfected children. After adjustment, black children had higher odds of Pri-LI versus no LI (adjusted odds ratio [aOR] = 2.43, p = .03). Children who were black, Hispanic, had a caregiver with low education or low intelligence quotient, or a nonbiological parent as caregiver had higher odds of Con-LI versus no LI. Among HIV+ children, viral load >400 copies/mL (aOR = 3.04, p < .001), Centers for Disease Control and Prevention Class C (aOR = 2.19, p = .02), and antiretroviral treatment initiation <6 months of age (aOR = 2.12, p = .02) were associated with higher odds of Con-LI versus no LI. CONCLUSIONS: Children perinatally exposed to HIV are at high risk for LI, but such risk was not increased for youth with HIV. Risk factors differed for Pri-LI and Con-LI.

Behavioral health risks in perinatally HIV-exposed youth: co-occurrence of sexual and drug use behavior, mental health problems, and nonadherence to antiretroviral treatment.

In a sample of perinatally HIV-infected (PHIV+) and perinatally HIV-exposed, uninfected (PHEU) adolescents, we examined the co-occurrence of behavioral health risks including mental health problems, onset of sexual and drug use behaviors, and (in PHIV+ youth) nonadherence to antiretroviral therapy (ART). Participants, recruited from 2007 to 2010, included 349 youth, ages 10-16 years, enrolled in a cohort study examining the impact of HIV infection and ART. Measures of the above behavioral health risks were administered to participants and primary caregivers. Nearly half the participants met study criteria for at least one behavioral health risk, most frequently, mental health problems (28%), with the onset of sexual activity and substance use each reported by an average of 16%. Among the sexually active, 65% of PHIV+ and 50% of PHEU youth reported unprotected sex. For PHIV +youth, 34% reported recent ART nonadherence, of whom 45% had detectable HIV RNA levels. Between 16% (PHIV+) and 11% (PHEU) of youth reported at least two behavioral health risks. Older age, but not HIV status, was associated with having two or more behavioral health risks versus none. Among PHIV+ youth, living with a birth mother (versus other caregivers) and detectable viral load were associated with co-occurrence of behavioral health risks. In conclusion, this study suggests that for both PHIV+ and PHEU youth, there are multiple behavioral health risks, particularly mental health problems, which should be targeted by service systems that can integrate prevention and treatment efforts.

Health behavior models in the age of mobile interventions: are our theories up to the task?

Mobile technologies are being used to deliver health behavior interventions. The study aims to determine how health behavior theories are applied to mobile interventions. This is a review of the theoretical basis and interactivity of mobile health behavior interventions. Many of the mobile health behavior interventions reviewed were predominately one way (i.e., mostly data input or informational output), but some have leveraged mobile technologies to provide just-in-time, interactive, and adaptive interventions. Most smoking and weight loss studies reported a theoretical basis for the mobile intervention, but most of the adherence and disease management studies did not. Mobile health behavior intervention development could benefit from greater application of health behavior theories. Current theories, however, appear inadequate to inform mobile intervention development as these interventions become more interactive and adaptive. Dynamic feedback system theories of health behavior can be developed utilizing longitudinal data from mobile devices and control systems engineering models.

Mental health functioning among children and adolescents with perinatal HIV infection and perinatal HIV exposure.

Mental health problems (MHPs) among children with perinatal HIV infection have been described prior to and during the highly active antiretroviral therapy (HAART) era. Yet child, caregiver and socio-demographic factors associated with MHPs are not fully understood. We examined the prevalence of MHPs among older children and adolescents with perinatal HIV exposure, including both perinatally HIV-infected (PHIV +) and perinatally HIV-exposed but uninfected (PHEU) youth. Our aims were to identify the impact of HIV infection by comparing PHIV + and PHEU youth and to delineate risk factors associated with MHPs, in order to inform development of appropriate prevention and intervention strategies. Youth and their caregivers were interviewed with the Behavior Assessment System for Children, 2nd edition (BASC-2) to estimate rates of at-risk and clinically significant MHPs, including caregiver-reported behavioral problems and youth-reported emotional problems. The prevalence of MHPs at the time of study entry was calculated for the group overall, as well as by HIV status and by demographic, child health, and caregiver characteristics. Logistic regression models were used to identify factors associated with youth MHPs. Among 416 youth enrolled between March 2007 and July 2009 (295 PHIV +, 121 PHEU), the overall prevalence of MHPs at entry was 29% and greater than expected based on recent national surveys of the general population. MHPs were more likely among PHEU than among PHIV + children (38% versus 25%, p < 0.01). Factors associated with higher odds of MHPs at p < 0.10 included caregiver characteristics (psychiatric disorder, limit-setting problems, health-related functional limitations) and child characteristics (younger age and lower IQ). These findings suggest that PHEU children are at high risk for MHPs, yet current models of care for these youth may not support early diagnosis and treatment. Family-based prevention and intervention programs for HIV affected youth and their caregivers may minimize long-term consequences of MHPs.

Assessing medication adherence of perinatally HIV-infected children using caregiver interviews.

Medication adherence is critical for children's HIV treatment success, but obtaining accurate assessments is challenging when complex measurement technologies are not feasible. Our goal was to evaluate a multidimensional adherence interview designed to improve on existing adherence measures. Data from caregivers (N = 126) of perinatally infected children were analyzed to determine the ability of the revised interview guide to detect potential treatment nonadherence. Questions related to viral load (VL) on a bivariate level included proportion of doses taken in the previous 3 days and 6 months, caregivers' knowledge of prescribed dosing frequencies, and caregivers' reports of problems associated with medication administration. VL was not associated with 3-day recall of missed doses. In multivariate analyses, only caregiver knowledge of prescribed dosing frequencies was uniquely associated with VL. Our modified interview appears to successfully identify family struggles with adherence and to have the capacity to help clinicians address medication adherence challenges.