Neuropsychological Correlates of Adherence in Youth with Behaviorally Acquired HIV.

Youth living with behaviorally acquired HIV (YLWH) are at-risk for both neuropsychological disorders and antiretroviral therapy (ART) non-adherence; little is known about their interrelationship over time in YLWH. Neuropsychological and psychiatric functioning, substance use, and self-report of 7-day/week and weekend ART adherence were assessed at baseline and Weeks 24, 48, 96 and 144 of a longitudinal study evaluating the impact of early (CD4>350) versus standard of care (CD4≤350) treatment initiation on neuropsychological functioning in 111 treatment-naïve YLWH age 18-24 years at entry. Bayesian multi-level models for adherence (≥ 90% vs. <90%) were fit using random intercepts for repeated measures. Adjusted odds ratios (OR [95% credible interval]) for higher versus lower baseline Motor function for visit adherence were 0.58 (0.25, 1.16), 0.5 (0.15, 1.38), 0.52 (0.16, 1.52), and 0.94 (0.3, 2.8) at Weeks 24, 48, 96, and 144, respectively. Week 24 adherence was associated with higher adjusted odds of Motor function at Week 48 (week: 0.27, -0.05-0.59; weekend: 0.28, -0.07-0.62). Week 96 Complex Executive functioning was associated with higher adjusted odds of adherence at Week 144, OR = 4.26 (1.50, 14.33). Higher Motor functioning emerged most consistently associated with lower odds of adherence in YLWH. Complex Executive functioning was associated with adherence only at end of study, suggesting potential contribution in adherence over the long-term.

The influence of religious beliefs and practices on health care decision-making among HIV positive adolescents.

It is unknown if religiousness/spirituality influences end-of-life treatment preferences among adolescents. Investigators assessed whether religiousness/spirituality moderates the relationship between an advance care planning intervention and end-of-life treatment preferences among 85 primarily African-American adolescents living with HIV/AIDS in outpatient-hospital-based HIV-specialty clinics in the United States. Adolescents aged 14-21 years living with HIV/AIDS and their families were randomized to three-weekly-60-minute sessions either: advance care planning (survey, goals of care conversation, advance directive); or control (developmental history, safety tips, nutrition/exercise). At 3-months post-intervention the intervention effect (decreasing the likelihood of choosing to continue treatments in all situations) was significantly moderated by religiousness/spirituality. Highly religious/spiritual adolescents were four times more likely to choose to continue treatments in all situations. Thus, intensive treatments at end-of-life may represent health equity, rather than health disparity. The belief believed that HIV is a punishment from God at baseline (15%, 14/94) was not associated with end-of-life treatment preferences. Twelve percent (11/94) reported they had stopped taking HIV medications for more than 3 days because of the belief in a miracle. Religiousness moderates adolescent's medical decision-making. Adolescents who believe in miracles should receive chaplaincy referrals to help maintain medication adherence.

The Effect of FAmily-CEntered (FACE®) Pediatric Advanced Care Planning Intervention on Family Anxiety: A Randomized Controlled Clinical Trial for Adolescents With HIV and Their Families.

Clinicians fear pediatric advance care planning (pACP) for adolescents is too distressing for families. Multisite longitudinal randomized controlled trial of adolescents with HIV tested the effect of FAmily-CEntered (FACE®) pACP intervention on families' anxiety and depression. One hundred five adolescent/family dyads were randomized to FACE® (n = 54 dyads) or control (n = 51 dyads). Families were 90% African American, 37% HIV-positive, and 22% less than high school educated. Families reported lower anxiety 3 months post-FACE® intervention than control (ß = -4.71, 95% confidence interval [CI] = [-8.20, -1.23], p = .008). Male family members were less anxious than female family members (ß = -4.55, 95% CI = [-6.96, -2.138], p ≤ .001). Family members living with HIV reported greater depressive symptoms than HIV-uninfected families (ß = 3.32, 95% CI = [0.254, 6.38], p = .034). Clinicians can be assured this structured, facilitated FACE® pACP model minimized family anxiety without increasing depressive symptoms. Adolescent/family dyads should be invited to have access to, and provision of, evidence-based pACP as part of patient-centered/family-supported care in the HIV continuum of care.

The Role of Pharmacy Refill Measures in Assessing Adherence and Predicting HIV Disease Markers in Youth with Perinatally-Acquired HIV (PHIV).

Antiretroviral (ARV) adherence is critical in monitoring disease response in youth with perinatally-acquired HIV (PHIV). We used pharmacy refill (PR) information for PHIV youth from the PHACS Memory Sub-study to calculate medication availability over 2, 4, and 6 months. PR, a proxy of adherence, was compared with self-reported 7-day adherence in predicting suppressed viral load (SVL < 400 copies/mL) and higher CD4% (≥ 25%). Among 159 PHIV youth, 79% were adherent by 7-day recall, and 62, 55, and 48% by PR over 2, 4, and 6 months, respectively. Agreement between 7-day recall and PR adherence was weak (Kappa = 0.09-0.25). In adjusted logistic regression models, adherence showed associations with SVL for 7-day recall (OR 2.78, 95% CI 1.08, 7.15) and all PR coverage periods (6-month: OR 3.24, 95% CI 1.22, 8.65). Similar associations were observed with higher CD4%. PR measures were predictive of study retention. Findings suggest a possibly independent role of PR adherence measures.

A randomized clinical trial of adolescents with HIV/AIDS: pediatric advance care planning.

The objective of this study is to determine if pediatric advance care planning (pACP) increases adolescent/family congruence in end-of-life (EOL) treatment preferences longitudinally. Adolescents aged 14-21 years with HIV/AIDS and their families were randomized (N = 105 dyads) to three-60-minute sessions scheduled one week apart: either the pACP intervention (survey administered independently, facilitated conversation with adolescent and family present, completion of legal advance directive document with adolescent and family present) or an active control (developmental history, safety tips, nutrition and exercise education). This longitudinal, single-blinded, multi-site, randomized controlled trial was conducted in six pediatric hospital-based HIV-clinics, located in high HIV mortality cities. The Statement of Treatment Preferences measured adolescent/family congruence in EOL treatment preferences at immediately following the facilitated pACP conversation (Session 2), and at 3-month post-intervention. The mean age of adolescent participants was 18 years (range 14-21 years); 54% were male; and 93% were African-American. One-third had an AIDS diagnosis. Immediately post-intervention the Prevalence Adjusted Bias Adjusted Kappa showed substantial treatment preference agreement for pACP dyads compared to controls (High burden/low chance of survival, PABAK = 0.688 vs. 0.335; Functional impairment, PABAK = 0.687 vs. PABAK= 0.34; Mental impairment, PABKA = 0.717 vs. 0.341). Agreement to limit treatments was greater among intervention dyads than controls (High burden: 14.6% vs. 0%; Functional impairment = 22.9% vs. 4.4%; and Mental impairment: 12.5% vs. 4.4%). Overall treatment preference agreement among pACP dyads was high immediately post-intervention, but decreased over time. In contrast, treatment agreement among control dyads was low and remained low over time. As goals of care change over time with real experiences, additional pACP conversations are needed.

Antiretroviral treatment initiation does not differentially alter neurocognitive functioning over time in youth with behaviorally acquired HIV.

Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18-24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n = 56); group 2 had CD4 >350 and were not initiating ART (n = 66); group 3 initiated ART with CD4 <350 (n = 59) per standard of care treatment guidelines at the time. Treatment was de-intensified to boosted protease inhibitor monotherapy at 48 weeks for those in group 1 with suppressed viral load. Covariates included demographic, behavioral, and medical history variables. Analyses used hierarchical linear modeling. All groups showed improved performance with peak at 96 weeks in all three functional domains. Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. In conclusion, YLWH showed improvement in neurocognitive functioning over time that may be related to practice effects and nonspecific impact of study participation. Neither improvement nor decline in functioning was associated with timing of ART initiation or therapy de-intensification.

Fetal growth assessed via ultrasound in relation to maternal HIV infection status and antiretroviral regimens.

OBJECTIVE: To evaluate effects of maternal HIV and antiretroviral treatment (ART) on intrauterine fetal growth. DESIGN: Prospective cohort studies of HIV and ZIKA infection among women living with HIV (WLHIV) and women not living with HIV (WNLHIV) conducted in Brazil and the US from 2016 to 2020. METHODS: We evaluated fetal growth via repeated ultrasounds and calculated z scores for fetal growth measures using Intergrowth-21st standards among women with singleton pregnancies. Adjusted linear mixed models were fit for each fetal growth z score by HIV status. Among WLHIV, we compared fetal growth z scores by the most common maternal ART regimens, stratified by timing of ART initiation. RESULTS: We included 166 WLHIV and 705 WNLHIV; none had Zika infection. The z scores were similar for WLHIV and WNLHIV for femur length (latest third trimester median = 1.08) and estimated fetal weight (median ≈0.60); adjusted mean differences in fetal weight z scores by HIV status were less than 0.1 throughout gestation. Other fetal growth measurements were lower for WLHIV than WNLHIV early in gestation but increased more rapidly over gestation. Among WLHIV not on ART at conception, adjusted mean z scores were generally similar across regimens initiated during pregnancy but somewhat lower for atazanavir-based regimens for biparietal diameter compared with efavirenz-based or raltegravir-based regimens. Among WLHIV on ART at conception, mean z scores were similar across ART regimens. CONCLUSION: Within our cohorts, fetal growth was lower in WLHIV than WNLHIV early in gestation but similar by the end of gestation, which is reassuring. Among WLHIV, fetal growth measures were generally similar across ART regimens evaluated.

Ageing with HIV: a longitudinal study of markers of resilience in young adults with perinatal exposure to HIV, with or without perinatally acquired HIV.

INTRODUCTION: Medical challenges, including perinatally acquired HIV (PHIV), can be considered adversity with the potential to compromise individuals' ability to meet societal expectations across the lifespan. Studies suggest that resilience, defined as positive adaptation in the context of adversity, helps individuals overcome challenges and improve their quality of life. Few longitudinal studies have examined resilience in young adults with perinatally acquired HIV (YAPHIV) or perinatal HIV exposure, uninfected (YAPHEU). We examined three young adult milestones, which can affect the life-long quality of life, as markers of resilience: high school graduation, postsecondary education and current employment. METHODS: Analyses included YAPHIV and YAPHEU, ages 19-27 years, followed in longitudinal cohort studies: Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (AMP) (7-17 years) and AMP Up (≥18 years). Factors known to influence the attainment of milestones (outcomes) were examined: executive function, cognitive efficiency (working memory and processing speed), behavioural/social-emotional functioning, parent/caregiver mental/physical health and cumulative risk. HIV disease markers for YAPHIV were examined. The most recent AMP assessment was used for each factor; outcomes were measured at AMP Up 1-year follow-up. Separate robust Poisson regression models were used to assess associations of each factor with each outcome; PHIV status was explored as an effect modifier of each association. RESULTS: Participants (N = 315; YAPHIV = 228): 58% female, 67% Black and 27% Hispanic. Compared to YAPHEU, YAPHIV were older and from families with higher median income and fewer symptoms of parent/caregiver mental health/substance use disorders. Proportions of YAPHIV and YAPHEU, respectively, who achieved each milestone were comparable: 82% versus 78% for high school graduation (p = 0.49), 45% versus 51% for postsecondary education (p = 0.35) and 48% versus 54% for current employment (p = 0.32). Higher cognitive efficiency was positively associated with postsecondary education and current employment. Higher executive function, age-appropriate behavioural/social-emotional functioning and lower cumulative risk were associated with academic milestones. Among YAPHIV, positive associations were: higher current CD4 with postsecondary education and lower nadir CD4 with current employment. PHIV status did not modify any association. CONCLUSIONS: YAPHIV and YAPHEU demonstrated resilience, attaining at least one young adult milestone. Cognitive, behavioural and social resources to support resilience in childhood and adolescence may provide the foundation for continued achievement throughout adulthood.

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.

An International Prospective Cohort Study of HIV and Zika in Infants and Pregnancy (HIV ZIP): Study Protocol.

Zika virus (ZIKV) infection may adversely affect pregnancies of women living with HIV (WLHIV). Because no study to date has focused on maternal and child effects of HIV and ZIKV co-infection in pregnant women, we undertook the International Prospective Cohort Study of HIV and Zika in Infants and Pregnancy (HIV ZIP). The aims of this two-phase study of pregnant women and their infants are to compare the incidence of ZIKV infection among pregnant women with and without HIV infection and to determine the risk of adverse maternal and child outcomes associated with ZIKV/HIV co-infection at clinical sites in Brazil, Puerto Rico, and the continental United States. Phase I was designed to enroll pregnant women/infant pairs who were: (1) infected with HIV only, (2) infected with ZIKV only, (3) infected with HIV and ZIKV, and (4) not infected with either HIV or ZIKV. A key goal of this phase was to assess the feasibility of enrolling 200 women/infant pairs within a year, with a target of 150 WLHIV, 50 HIV-uninfected women, and a minimum of 20 who were co-infected with HIV and ZIKV. If the feasibility of Phase I proved successful, Phase II would enroll up to 1,800 additional pregnant women/infant pairs to the same four groups. Enrolled women in both phases were to be followed throughout their pregnancy and up to 6 weeks post-partum. Infants were also to be followed for 1 year after birth. To date, Phase 1 data collection and follow-up have been completed. Delineation of possible harmful effects of HIV/ZIKV co-infection will allow the formulation of standard-of-care recommendations to minimize adverse effects but enable the continuation of preventive HIV therapy. Furthermore, while the prospective HIV ZIP study was developed before the COVID pandemic, it is especially relevant today since it can be easily adapted to provide critically important information on the impact of COVID-19 infection or other still unrecognized new agents among pregnant women and their offspring worldwide.

Racial/Ethnic Disparities in Longitudinal Emotional-Behavioral Functioning Among Youth Born to Women Living With HIV.

BACKGROUND: Youth with perinatal HIV exposure have demonstrated high rates of emotional-behavioral problems. Few studies have longitudinally examined racial/ethnic disparities in such functioning across adolescence, a critical time for targeting prevention/intervention efforts. SETTING: The Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol is one of the largest US-based cohort studies of youth with perinatal HIV (YPHIV) infection or HIV exposed but uninfected (YPHEU). METHODS: Youth and caregivers individually completed the Behavior Assessment System for Children, second edition, every 2 years between ages 7 and 19 years. We used adjusted mixed-effects models to evaluate whether mean youth-reported emotional concerns and caregiver-reported behavioral concerns differed by race/ethnicity. We used group-based trajectory models to identify groups having similar emotional-behavioral trajectories, followed by multinomial models to determine which factors predicted group membership. RESULTS: Three hundred ninety-one YPHIV and 209 YPHEU (7% White non-Hispanic, 21% White Hispanic, 66% Black non-Hispanic, and 6% Black Hispanic) completed a median of 4 assessments over follow-up. Adjusted models showed more caregiver-reported behavioral concerns for Black non-Hispanic YPHEU than for Black non-Hispanic YPHIV, White Hispanic YPHIV, and White Hispanic YPHEU, particularly later in adolescence. Race/ethnicity did not predict membership in subgroups of youth-reported emotional or caregiver-reported behavioral functioning identified using group-based trajectory models. However, factors predicting membership in vulnerable youth-reported emotional and caregiver-reported behavioral groups included experiencing a stressful life event and living with a caregiver who was married or screened positive for a psychiatric condition. CONCLUSIONS: Our study revealed that Black non-Hispanic YPHEU are a vulnerable subgroup. Contributing factors that could inform interventions include the caregiver's health, household characteristics, and psychiatric status.

Trajectories of Depressive Symptoms, Neurocognitive Function, and Viral Suppression With Antiretroviral Therapy Among Youth With HIV Over 36 months.

BACKGROUND: Depression and neurocognitive impairment are highly prevalent among persons living with HIV and associated with poorer clinical outcomes; however, longitudinal studies of depression-neurocognition relationships in youth living with HIV (YLWH), and the role of antiretroviral therapy (ART), are lacking. This study tested whether (1) depressive symptomatology, across somatic, cognitive, and affective symptom domains, improved with ART and (2) more severe depressive symptoms at baseline were associated with poorer neurocognitive function and poorer HIV suppression. SETTING: Data were collected from 181 YLWH (18-24 years) who were treatment-naive, a subset of whom (n = 116) initiated ART. METHODS: Participants were categorized into elevated (DS) or nonelevated (non-DS) depressive symptom groups at entry (Beck Depression Inventory-II ≥14) and followed for 36 months. Neurocognition (5-domain battery) and depressive symptoms were repeatedly assessed. Longitudinal models examined depressive symptomatology, neurocognition, and odds of HIV nonsuppression by group. RESULTS: Greater improvements in depressive symptoms were observed in the DS group over 36 months [beta = -0.14, (-0.24 to -0.03)], particularly within cognitive and affective domains. Verbal learning performance increased in the DS group [beta = 0.13, (0.01 to 0.24)], whereas psychomotor function improved somewhat in the non-DS group [beta = -0.10, (-0.22 to 0.00)]. Adjusted for ART adherence, odds of HIV nonsuppression did not significantly differ by group [odds ratio = 0.22, (0.04 to 1.23)]; however, greater somatic symptoms at study entry were associated with an increased risk of nonsuppression over time [odds ratio = 2.33 (1.07 to 5.68)]. CONCLUSION: Depressive symptoms were associated with differential neurocognitive trajectories, and somatic depressive symptoms at baseline may predict poorer subsequent HIV suppression. Identifying and treating depressive symptoms at ART initiation may benefit neurocognitive and clinical outcomes in YLWH.

Allocation of family responsibility for illness management in pediatric HIV.

OBJECTIVE: The purpose of the study is to describe allocation of responsibility for illness management in families of children and adolescents perinatally infected with HIV. METHODS: A total of 123 youth (ages 8-18) and caregivers completed family responsibility and medication adherence questionnaires as part of a substudy of Pediatric AIDS Clinical Trials Group protocol 219c. RESULTS: Approximately one-fourth of the youth reported being fully responsible for taking medications. A smaller percentage of caregivers reported full youth responsibility. Older youth and caregivers of older youth reported higher degree of youth responsibility for medication-related tasks, though age was unrelated to adherence. Caregiver report of greater responsibility for medications was associated with better adherence. CONCLUSIONS: Caregivers are likely to transition responsibility for HIV care to older youth but this transition was not always successful as evidenced by poor medication adherence. Interventions supporting successful transition may improve adherence and subsequently health outcomes in pediatric HIV.

Paediatric advance care planning survey: a cross-sectional examination of congruence and discordance between adolescents with HIV/AIDS and their families.

OBJECTIVES: To identify patient-reported paediatric advance care planning (pACP) needs of adolescents living with HIV and to examine the congruence with their family's perception of their needs. METHODS: A cross-sectional survey among six paediatric hospital-based outpatient HIV specialty clinics. Participants included 48 adolescent/family dyads (n=96 participants) within a larger study facilitating pACP. The main outcome measure was the Lyon Advance Care Planning Survey - Adolescent and Surrogate Versions-Revised. RESULTS: Adolescents' mean age was 18 years (range ≥14-<21); 54% male; 92% African-American; 27% with prior AIDS diagnosis. If dying, 92% believed in completing an advance directive; 85% preferred to die at home;88% knowing how to say good bye; 71% being off machines that extend life and 77% dying a natural death. Best timing for end-of-life (EOL) decisions was while healthy (38%), when first diagnosed (17%), when first sick from a life-threatening illness (4%), when first hospitalised (8%), if dying (4%) and all of the above (19%). Prevalence-adjusted bias-adjusted Kappa (PABAK) measured congruence in pACP needs within adolescent/family dyads. There was substantial congruence in that being free from pain (PABAK=0.83), and understanding your treatment choices (PABAK=0.92) were very important or important. There was discordance about being off machines that extend life (PABAK=0.08) and when is the best time to bring up EOL decisions (PABAK=0.32). CONCLUSIONS: Areas of discordance were associated with life-sustaining choices and when to have the EOL conversation. Targeted, adolescent/family-centred, evidence-based pACP interventions are needed to improve family understanding of youth's EOL wishes. TRIAL REGISTRATION NUMBER: NCT01289444; Results.

Development and reliability of the Prospective Memory Assessment for Children & Youth (PROMACY): A preliminary study in a nonclinical sample.

Prospective memory (PM), "remembering to remember," has been linked to important functional outcomes in adults. Studies of PM in children and adolescents would benefit from the development and validation of developmentally appropriate clinical measures with known psychometric properties. The Prospective Memory Assessment for Children & Youth (PROMACY), a performance-based measure of PM, was developed for the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, Memory and Executive Functioning Substudy, and includes Summary, Time-, and Event-based scores derived from eight trials with an ongoing word search task. Fifty-four healthy perinatally HIV-exposed, uninfected children and youth, mean age 13 years, 54% female, 76% Black/non-Hispanic, and 61% impoverished were included in this psychometric analysis. PROMACY Summary Scores demonstrated low, but broadly acceptable internal consistency as measured by Cronbach's alpha and Spearman-Brown. Better PROMACY performance was associated with older age, but no other demographic factors. Generally medium-sized correlations were observed between the PROMACY Summary Score and standard clinical measures of retrospective memory, working memory, executive functions, and IQ. Findings from this preliminary psychometric study of nonclinical children and youth provide cautious support for the internal consistency and construct validity of PROMACY's Summary Score that awaits replication and extension in larger samples of healthy children, youth and clinical populations.

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.

Higher soluble CD14 levels are associated with lower visuospatial memory performance in youth with HIV.

OBJECTIVE: HIV-associated neurocognitive disorders persist despite early antiretroviral therapy (ART) and optimal viral suppression. We examined the relationship between immunopathogenesis driven by various pathways of immune activation and discrete neurocognitive performance domains in youth with HIV (YWH). DESIGN: Observational cross-sectional study. METHODS: YWH, ages 20-28 years, enrolled in Adolescent Medicine Trials Network 071/101 were assessed for biomarkers of macrophage, lymphocyte activation, and vascular inflammation using ELISA/multiplex assays. Standardized neurocognitive tests were performed, and demographically adjusted z-scores were combined to form indices of attention, motor, executive function, verbal, and visuospatial memory. Cross-sectional analysis of the relationship between 18 plasma inflammatory biomarkers and each neurocognitive domain was performed. Linear regression models were fit for each combination of log-transformed biomarker value and neurocognitive domain score, and were adjusted for demographics, socioeconomic status, substance use, depression, CD4 T-cell count, HIV viral load, and ART status. RESULTS: Study included 128 YWH [mean age 23.8 (SD 1.7) years, 86% men, 68% African American]. Verbal and visuospatial memory domains were most significantly impaired in the cohort (z = -1.59 and -1.0, respectively). Higher sCD14 was associated with impaired visuospatial memory, which remained robust after adjusting for other biomarkers, demographics, and HIV-associated covariates. Among biomarkers of vascular inflammation, sICAM-1 was negatively associated with verbal memory and attention, whereas sVCAM-1 was positively associated with executive function and visuospatial memory. Specific neurocognitive domains were not associated with sCD163, LPS, or CCL2 levels. CONCLUSION: Impaired visuospatial memory in YWH is associated with immune activation, as reflected by higher sCD14.

Prospective memory in youth with perinatally-acquired HIV infection.

Youth with perinatal HIV infection (PHIV) are at increased risk for neurocognitive impairment (NCI). Prospective memory (PM) is a complex neurocognitive function that has been shown to be impaired in adults with HIV disease and independently associated with poorer daily living skills, including medication nonadherence. The current study sought to determine the presence and extent of PM deficits in youth with PHIV. Participants included 173 youth with PHIV and 85 youth perinatally HIV-exposed but uninfected (PHEU), mean age 14.1 years, 75% black, 18% Hispanic. Among youth with PHIV, 26% had a past AIDS-defining condition (Centers for Disease Control and Prevention [CDC], Class C), 74% did not (non-C). Adjusted generalized estimating equation models were used to compare groups (PHIV/C, PHIV/non-C, and PHEU) on the Naturalistic Event-Based Prospective Memory Test (NEPT) and the Prospective Memory Assessment for Children & Youth (PROMACY). Secondarily, subgroups defined by HIV serostatus and global NCI were compared (PHIV/NCI, PHIV/non-NCI, PHEU). PHIV/C had significantly lower NEPT scores than PHEU, with decreases of 40% in mean scores, but did not differ from PHIV/non-C. PHIV/NCI had 11-32% lower PROMACY scores and 33% lower NEPT scores compared to PHIV/non-NCI (all p < .05); significantly, lower scores for PHIV/NCI versus PHEU also were observed for PROMACY and NEPT indices. Findings suggest a subset of youth with PHIV (those with a prior AIDS-defining diagnosis) is vulnerable to PM deficits. The extent to which PM deficits interfere with development and maintenance of independent living and health-related behaviors during transition to adulthood requires further study.

Advance Care Planning and HIV Symptoms in Adolescence.

OBJECTIVES: To determine the effect of family-centered pediatric advance care planning (FACE pACP) on HIV-specific symptoms. METHODS: In this single-blinded, randomized controlled trial conducted at 6 US hospital-based HIV clinics, 105 adolescent-family dyads, randomly assigned from July 2011 to June 2014, received 3 weekly sessions in either the FACE pACP arm ([1] pediatric advance care planning survey, [2] Respecting Choices interview, and [3] 5 Wishes directive) or the control arm ([1] developmental history, [2] safety tips, and [3] nutrition and exercise tips). The General Health Assessment for Children measured patient-reported HIV-specific symptoms. Latent class analyses clustered individual patients based on symptom patterns. Path analysis examined the mediating role of dyadic treatment congruence with respect to the intervention effect on symptom patterns. RESULTS: Patients were a mean age of 17.8 years old, 54% male, and 93% African American. Latent class analysis identified 2 latent HIV-symptom classes at 12 months: higher symptoms and suffering (27%) and lower symptoms and suffering (73%). FACE pACP had a positive effect on dyadic treatment congruence (ß = .65; 95% CI: 0.04 to 1.28), and higher treatment congruence had a negative effect on symptoms and suffering (ß = -1.14; 95% CI: -2.55 to -0.24). Therefore, FACE pACP decreased the likelihood of symptoms and suffering through better dyadic treatment congruence (ß = -.69; 95% CI: -2.14 to -0.006). Higher religiousness (ß = 2.19; 95% CI: 0.22 to 4.70) predicted symptoms and suffering. CONCLUSIONS: FACE pACP increased and maintained agreement about goals of care longitudinally, which lowered adolescents' physical symptoms and suffering, suggesting that early pACP is worthwhile.

Impact of Perinatally Acquired HIV Disease Upon Longitudinal Changes in Memory and Executive Functioning.

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 -0.99 (95% CI: -1.80 to -0.19; 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.