Patricia A. Garvie

Impact of HIV severity on cognitive and adaptive functioning during childhood and adolescence.

Background: The influence of disease severity on cognitive and adaptive functioning in perinatally HIV-infected youth with (PHIV+/C) and without (PHIV+/NoC) a previous AIDS-defining illness (Centers for Disease Control and Prevention Class C event), compared with perinatally HIV-exposed but uninfected youth (PHEU) is not well understood. Methods: This was a cross-sectional analysis of cognitive and adaptive functioning in PHIV+/C (n = 88), PHIV+/NoC (n = 270) and PHEU (n = 200) youth aged 7–16 years, from a multisite prospective cohort study. Youth and caregivers completed the Wechsler Intelligence Scale for Children, Fourth Edition and the Adaptive Behavior Assessment System, Second Edition, respectively. We compared means and rates of impairment between groups, and examined associations with other psychosocial factors. Results: Overall mean scores on measures of cognitive and adaptive functioning were in the low average range for all 3 groups. After adjustment for covariates, mean full-scale intelligence quotient scores were significantly lower for the PHIV+/C group than the PHIV+/NoC and PHEU groups (mean = 77.8 versus 83.4 and 83.3, respectively), whereas no significant differences were observed between the PHEU and PHIV+/NoC groups in any domain. Lower cognitive performance for the PHIV+/C group was primarily attributable to a prior diagnosis of encephalopathy. No significant differences between groups were observed in adaptive functioning. Conclusion: For long-term survivors, youth with HIV infection and a prior Centers for Disease Control and Prevention Class C event have higher risk for cognitive but not adaptive impairment regardless of current health status; this finding appears attributable to a previous diagnosis of encephalopathy. Early preventive therapy may be critical in reducing risk of later neurodevelopmental impairments.

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.

Who Will Speak for Me? Improving End-of-Life Decision-Making for Adolescents With HIV and Their Families

OBJECTIVES. The purpose of this research was to test the effectiveness of a model of family/adolescent-centered advance care planning for adolescents living with HIV and their families for increasing congruence and quality of communication while decreasing decisional conflict. PATIENTS AND METHODS. Ours was a 2-group, randomized, controlled trial in 2 hospital-based outpatient clinics in Washington and Memphis from 2006 to 2008. Participants (N = 38 dyads) included medically stable adolescents aged 14 to 21 years with HIV/AIDS and surrogates/families aged ≥21 years. Three 60- to 90-minute sessions were conducted 1 week apart via a semistructured family interview with a trained/certified interviewer. Each session encompassed, respectively: (1) Lyon Advance Care Planning Survey; (2) Respecting Choices interview; and (3) Five Wishes. Controls received (1) developmental history, (2) safety tips, and (3) future plans. Family congruence was measured by the Statement of Treatment Preferences and adolescent decisional conflict by the Decisional Conflict Scale, immediately after session 2. Communication was measured by the Quality of Participant-Interviewer Communication Scale after each session. RESULTS. Adolescent demographics were as follows: mean age was 16 years; 40% were boys; 92% were black; HIV transmission rate was 68% perinatal and 32% sexually acquired; 42% were asymptomatic; 29% were symptomatic; and 29% had a diagnosis of AIDS. Significantly increased congruence for testing the difference of the 2 κ values for the 2 conditions was observed for intervention versus control dyads. Intervention adolescents reported feeling significantly better informed about end-of-life decisions. Intervention adolescents and all of the surrogates were more likely to feel that their attitudes and wishes were known by the interviewer over time. Intervention families, significantly more so than controls, rated the overall quality of discussion as very good to excellent. CONCLUSIONS. Family-centered advance care planning by trained facilitators increased congruence in adolescent/surrogate preferences for end-of-life care, decreased decisional conflict, and enhanced communication quality. Families acknowledged a life-threatening condition and were willing to initiate end-of-life conversations when their adolescents were medically stable.

Efficacy of a pill-swallowing training intervention to improve antiretroviral medication adherence in pediatric patients with HIV / AIDS.

OBJECTIVE. We aimed to retrospectively assess the efficacy of pill-swallowing training provided as a clinical intervention to referred pediatric patients with HIV in relation to improved adherence and subsequent related health outcomes. The primary goal of this study was to demonstrate participation in pill-swallowing training is associated with improved medication adherence as documented by routine pharmacy pill counts. Secondary objectives were to assess corresponding improvements in clinically observed biologic indicators of adherence, specifically, immunologic functioning (CD4+ T-cell%) and viral load, over time. PATIENTS AND METHODS. A retrospective chart review of 23 pediatric patients with HIV aged 4 to 21 years who were clinically referred for pill-swallowing training by an experienced pediatric psychologist for either noted difficulties with currently prescribed antiretroviral regimens and/or desire to change the childs regimen/formulary. Patient demographics, reason(s) for pill-swallowing training referral, number of pill-swallowing training sessions required to attain success, adherence, CD4+ T-cell%, and viral load were abstracted at baseline and at ∼3 and 6 months posttraining. RESULTS. Modal number of sessions required to acquire the pill-swallowing skill was 1 session. Younger children (aged 4–5 years) required a median of 2 training sessions, while older children required ≥3 sessions. A significant improvement in adherence from baseline to 6 months post–pill-swallowing training completion was observed, as were significant related improvements in CD4+ T-cell% and viral load. CONCLUSIONS. Participation in pill-swallowing training related to improved medication adherence at 6 months posttraining. Subsequent improvements in related CD4+ T-cell% and viral load were noted over time, most significantly at 6 months postintervention. These preliminary findings provide justification for additional study via a prospective, randomized, controlled clinical trial. Pill-swallowing training potentially is a successful time-limited, cost-effective intervention to improve adherence to antiretroviral therapies, and thus medical status, in children with HIV.

Barriers to Medication Adherence in HIV-Infected Children and Youth Based on Self- and Caregiver Report

OBJECTIVE: Nonadherence to antiretroviral therapy among children/youth with HIV often is associated with disease progression. This study examined the agreement between child and caregiver perceptions of barriers to adherence and factors associated with these barriers. METHODS: Children/youth with perinatally acquired HIV and their parents/caregivers (n = 120 dyads) completed a questionnaire about 19 potential barriers to adherence to the child’s antiretroviral therapy regimen. Agreement between the 2 reports was measured via the kappa statistic. Factors associated with the barriers were assessed by using multiple logistic regression. RESULTS: Of the 120 children, 55% were African American, 54% were boys, and the average age was 12.8 years. The most frequently reported barrier by either the caregiver or youth was “forgot.” There were varying degrees of agreement between child and caregiver on the following barriers: “forgot,” “taste,” “child was away from home,” “child refused,” and “child felt good.” Children who knew their HIV status were more likely to report logistical barriers, such as scheduling issues. Children with a biological parent as their caregiver were more likely to report regimen or fear of disclosure as a barrier. CONCLUSIONS: Lack of agreement was observed for more than half of the studied barriers, indicating discrepancies between children’s and caregivers’ perceptions of factors that influence medication-taking. The findings suggest a need for interventions that involve both child and caregiver in the tasks of remembering when to administer the child’s medications, sustaining adherence, and appropriately transitioning medication responsibility to the youth.

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.

Therapy preference and decision-making among patients with severe sickle cell anemia and their families&

Patients with severe sickle cell anemia (SCA) may benefit from therapeutic intervention with hydroxyurea (HU), chronic red cell transfusion (CT), or stem cell transplantation (SCT). Determination of best treatment is complicated by the tradeoff between each treatments risks and benefits and the lack of data comparing them to determine efficacy. We explored factors that influenced making decisions regarding interventions and examined the relations between treatment preference and health‐related quality of life (HRQOL).

Assessment of adherence to antiretroviral therapy in perinatally HIV-infected children and youth using self-report measures and pill count.

Background: Parent/caregiver or child/youth self-report and pill counts are commonly used methods for assessing adherence to antiretroviral therapy among children and youth with HIV. The purpose of this study was to compare these different methods with one another and with viral load. Methods: Randomly selected parent/caregiver and child/youth dyads were interviewed using several adherence self-report measures and an announced pill count was performed. Adherence assessment methods were compared with one another and their relative validity was assessed by comparison with the child’s viral load close to the time of the interview or pill count, adjusting for primary caregiver, child age, and child disclosure of the diagnosis. Results: There were 151 evaluable participants. Adherence rate by pill count was ≥90% in 52% of participants, was significantly associated with log(RNA) viral load (p = .032), and had significant agreement with viral load <400 copies/mL. However, pill count data were incomplete for 26% of participants. With similar proportions considered adherent, a variety of self-report adherence assessment methods also were associated with log(RNA) viral load including: “no dose missed within the past 1 month” (p = .054 child/youth interview, p = .004 parent/caregiver interview), and no barrier to adherence identified (p = .085 child/youth interview, p = .015 parent/caregiver interview). Within-rater and inter-rater agreement was high among self-report methods. Three day recall of missed doses was not associated with viral load. Conclusion: Findings demonstrate the validity of adherence assessment strategies that allow the parent/caregiver or child/youth to report on adherence over a longer period of time and to identify adherence barriers. Adherence assessed by announced pill count was robustly associated with viral load, but there was incomplete data for many participants.

Safety of perinatal exposure to antiretroviral medications: developmental outcomes in infants.

Background: This study evaluated effects of perinatal exposure to antiretroviral (ARV) medications on neurodevelopment of HIV-exposed, uninfected infants. Methods: HIV-exposed, uninfected infants (age 9–15 months) enrolled in Surveillance Monitoring for Antiretroviral Therapy Toxicities, a multisite prospective surveillance study, completed the Bayley Scales of Infant and Toddler Development—Third Edition (Bayley-III), assessing cognition, language, motor skills, social-emotional development and adaptive behavior. Linear regression models were used to evaluate associations between Bayley-III outcomes in infants with and without perinatal and neonatal ARV exposure, by regimen (combination ARV [cARV] versus non-cARV), type of regimen (defined by drug class) and individual ARVs (for infants with cARV exposure), adjusting for maternal and infant health and demographic covariates. Results: As of May 2010, 374 infants had valid Bayley-III evaluations. Median age at testing was 12.7 months; 49% male, 79% black and 16% Hispanic. Seventy-nine percent were exposed to regimens containing protease inhibitors (9% of protease inhibitor–containing regimens also included non-nucleoside reverse transcriptase inhibitors), 5% to regimens containing non-nucleoside reverse transcriptase inhibitors (without protease inhibitor) and 14% to regimens containing only nucleoside reverse transcriptase inhibitors. Overall, 83% were exposed to cARV. No Bayley-III outcome was significantly associated with overall exposure to cARV, ARV regimen or neonatal prophylaxis. For individual ARVs, following sensitivity analyses, the adjusted group mean on the Language domain was within age expectations but significantly lower for infants with perinatal exposure to atazanavir (P = 0.01). Conclusions: These results support the safety of perinatal ARV use. Continued monitoring for adverse neurodevelopmental outcomes in older children is warranted, and the safety of atazanavir merits further study.

Concordance between self-reported substance use and toxicology among HIV-infected and uninfected at risk youth

BACKGROUND Substance use by youth living with HIV (YLWH) is a concern, given potential interactions with virus-associated immune suppression and adverse effects on risk behaviors, neurocognition, and adherence. Self-report substance use measures provide efficient cost-effective assessments. Analyses describe self-reported substance use among YLWH and examine agreement with toxicology assays. METHODS Seventy-eight youth age 18-24 years (87% male, 71% African-American) with behaviorally acquired HIV-1 infection and 55 uninfected youth completed the Alcohol, Smoking, and Substance Involvement Screening Test to assess drug use frequency, including tobacco, marijuana, cocaine, and alcohol, over the prior three months. Elisa-based toxicology assays were used to detect 27 substances in plasma. Chi-square tests compared substance use between YLWH and uninfected youth; Kappa statistics compared agreement between self-report and toxicology. RESULTS YLWH reported marijuana (49%), tobacco (56%), and alcohol (87%) use, with 20%, 28% and 3% reporting daily use of each substance, respectively; other substance use was uncommon. Uninfected youth reported less tobacco use but otherwise similar substance use. All youth who reported daily use of marijuana or tobacco had positive plasma toxicology results, while concordance decreased with less frequent self-reported use. Among youth reporting no substance use, few tested positive (4% YLWH, 2% uninfected youth for cannabis; 8%YLWH for tobacco). CONCLUSIONS Youth report high rates of marijuana, tobacco, and alcohol use. Concordance between self-report and toxicology for marijuana and tobacco use, particularly for daily users, supports self-report as a valid indicator of substance use in research studies of youth with or without HIV-1 infection.