Deborah S. Storm

Predictors of Adherence to Antiretroviral Medications in Children and Adolescents With HIV Infection

BACKGROUND. Most evaluations of adherence to antiretroviral therapy in children with HIV infection have focused on validation of adherence measures via their association with virological outcomes. However, few studies have fully explored associations with other factors to guide development of adherence interventions. METHODS. In this study, we examined the relationship of self-reported medication adherence to health, demographic, and psychosocial characteristics of children and their caregivers, using data from an ongoing multicenter prospective observational study of long-term outcomes of HIV infection conducted by the Pediatric AIDS Clinical Trials Group. Child and caregiver characteristics were evaluated for association with adherence via univariate and multiple logistic regression models. RESULTS. Of the 2088 children and adolescents, 84% reported complete adherence to antiretroviral therapy medications over the past 3 days. The median viral load was ∼10 times higher among nonadherent than adherent children, and the strength of this association increased with age. Factors associated with at least marginally significant increases in nonadherence in a multiple logistic regression model included increasing age in years, female gender, detectable HIV viral load, occurrence of recent stressful life events, repeating a grade in school, self-assessment of adherence by the subject, and diagnosis of depression or anxiety. Having an adult other than the biological parent as the primary caregiver, using a buddy system to remember to take antiretroviral therapy medications, higher caregiver education level, previous adherence assessments, and taking antipsychotic medications were each associated with improved adherence. After controlling for these characteristics, there was no significant association of adherence with race, knowledge of HIV status, medication burden, CD4 percentage, or current antiretroviral therapy. CONCLUSIONS. Rates of self-reported adherence were relatively high and were influenced by multiple child and family characteristics. These findings identify targets for adherence interventions and highlight the importance of evaluating and supporting the family environment to optimize adherence.

Impact of Disclosure of HIV Infection on Health-Related Quality of Life Among Children and Adolescents With HIV Infection

BACKGROUND. Little is known concerning the impact of HIV status disclosure on quality of life, leaving clinicians and families to rely on research of children with other terminal illnesses. OBJECTIVES. The purpose of this work was to examine the impact of HIV disclosure on pediatric quality of life and to describe the distribution of age at disclosure in a perinatally infected pediatric population. METHODS. A longitudinal analysis was conducted of perinatally HIV-infected youth ≥5 years of age enrolled in a prospective cohort study, Pediatric AIDS Clinical Trials Group 219C, with ≥1 study visit before and after HIV disclosure. Age-specific quality-of-life instruments were completed by primary caregivers at routine study visits. The distribution of age at disclosure was summarized. Six quality-of-life domains were assessed, including general health perception, symptom distress, psychological status, health care utilization, physical functioning, and social/role functioning. For each domain, mixed-effects models were fit to estimate the effect of disclosure on quality of life. RESULTS. A total of 395 children with 2423 study visits were analyzed (1317 predisclosure visits and 1106 postdisclosure visits). The median age at disclosure was estimated to be 11 years. Older age at disclosure was associated with earlier year of birth. Mean domain scores were not significantly different at the last undisclosed visit compared with the first disclosed visit, with the exception of general health perception. When all of the visits were considered, 5 of 6 mean domain scores were lower after disclosure, although the differences were not significant. In mixed-effects models, disclosure did not significantly impact quality of life for any domain. CONCLUSIONS. Age at disclosure decreased significantly over time. There were no statistically significant differences between predisclosure and postdisclosure quality of life; therefore, disclosure should be encouraged at an appropriate time.

Protease Inhibitor Combination Therapy, Severity of Illness, and Quality of Life Among Children With Perinatally Acquired HIV-1 Infection

Objectives. This study examines quality of life (QOL) among school-aged children with perinatally acquired HIV infection and compares QOL outcomes between treatment groups that differ according to the use of protease inhibitor (PI) combination therapy (PI therapy). To gain insights into how PI therapy might influence QOL, associations between severity of illness and QOL were also investigated. Methods. Cross-sectional data for 940 children, 5 to 18 years of age, who were enrolled in Pediatric AIDS Clinical Trials Group Late Outcomes Protocol 219 were used to examine domains of caregiver-reported QOL, as assessed with the General Health Assessment for Children, during 1999. The General Health Assessment for Children is an age-specific, modular, QOL assessment that was developed for the study with previously validated measures. QOL differences between treatment groups were estimated with linear and logistic regressions that controlled for sociodemographic characteristics (age, gender, race/ethnicity, maternal/caregiver education, and respondent) and severity-of-illness indicators related to receipt of PI therapy (AIDS status, log10 CD4+ cell counts, and height-for-age z scores). Results. The mean age of participants was 9.7 years. Most children were non-Hispanic black (54%) or Hispanic (31%), and 49% of the participants were female. At the 1999 study visit, ∼14% of children had severe immune suppression (<15% CD4+ cells), whereas 62% of children had ≥25% CD4+ cells, ie, no immune suppression. Participants did exhibit some lag in growth, with mean height and weight z scores of −0.70 and −0.20, respectively. Twenty-eight percent of the children were reported to have met criteria for AIDS at study entry (1993–1999). When treatment groups were compared, children receiving PI therapy (72%) were older, had lower CD4+ cell percentages, and had lower height and weight z scores than did those receiving non-PI therapies. They were also more likely to have met criteria for AIDS at study entry. The most commonly used PIs were ritonavir (46%) and nelfinavir (63%). Health perceptions ratings for most children were at the upper end of the scale, whereas ratings for 25% of the children ranged over the lower 70% of scale scores. Almost one half of the children had at least some limitations in physical functioning, with more frequent limitations in energy-demanding activities (46%) than in basic activities of daily living (32%). The Behavior Problems Index was used to assess psychologic functioning. The mean total Behavior Problems Index score (9.34) and the proportion of children with extreme scores (23%) were consistent with values reported for chronically ill children and those at social and economic risk. One or more limitations in social/school functioning were reported for 58% of children. More than one third of the children (38%) experienced ≥1 physical symptoms that were at least moderately distressing. Health perceptions, physical functioning, psychologic functioning, social/school functioning, and overall HIV symptom scores did not differ between treatment groups. However, receipt of PI therapy was associated with an increased rate of diarrhea (28 vs 13%; adjusted odds ratio: 2.59; 95% confidence interval: 1.74–3.85). Severity of illness was associated with QOL in all domains except psychologic functioning. Higher log10 CD4+ cell counts, higher height-for-age z scores, and absence of AIDS at study entry were independently associated with fewer social/school limitations and better HIV symptom scores. Health perceptions and physical functioning scores were associated with log10 CD4+ cell counts and height z scores, respectively. Conclusions. QOL among children receiving PI therapy differed little from that among children receiving non-PI therapy, despite clinical indications of more advanced disease. Importantly, the study found no evidence of direct negative effects of PI therapy on QOL outcomes, other than an increased rate of diarrhea. Findings suggest that the effects of PI combination therapies to slow or to prevent disease progression and to increase CD4+ cell counts and height growth have the potential to improve QOL among children with HIV infection. However, many children do experience a constellation of functional impairments indicated by behavioral problems and clinical symptoms, with limitations in activities and in school performance. Comprehensive health services will continue to be required to minimize long-term illness and disability and to maximize childrens potential as they move into adolescence and adulthood.

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.

Medication Adherence in Children and Adolescents with HIV Infection: Associations with Behavioral Impairment

The impact of behavioral functioning on medication adherence in children with perinatally acquired HIV infection is not well-explored, but has important implications for intervention. This report addresses the relationship between behavioral functioning and child self-report or caregiver report of medication adherence among children and adolescents enrolled in Pediatric AIDS Clinical Trials Group Protocol 219C (conducted 2000-2007). A total of 1134 participants, aged 3-17 years, received a behavioral evaluation and adherence assessment. Complete adherence was defined as taking 100% of prescribed antiretroviral medications during three days preceding the study visit. Multivariable logistic regression models were used to evaluate associations between adherence and behavioral functioning, adjusting for potential confounders, including demographic, psychosocial, and health factors. Children demonstrated higher than expected rates of behavioral impairment (≈7% expected with T > 65) in the areas of conduct problems (14%, z = 7.0, p < 0.001), learning problems (22%, z = 12.2, p < 0.001), somatic complaints (22%, z = 12.6, p < 0.001), impulsivity-hyperactivity (20%, z = 11.1, p < 0.001), and hyperactivity (19%, z = 10.6, p < 0.001). Children with behavioral impairment in one or more areas had significantly increased odds of nonadherence [adjusted odds ratio (aOR) = 1.49, p = 0.04]. The odds of nonadherence were significantly higher for those with conduct problems and general hyperactivity (aOR = 2.03, p = 0.005 and aOR = 1.68, p = 0.02, respectively). Psychosocial and health factors, such as recent stressful life events and higher HIV RNA levels, were also associated with nonadherence. Knowledge of behavioral, health, and social influences affecting the child and family should guide the development of appropriate, evidence-based interventions for medication adherence.

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.

Preconception and Contraceptive Care for Women Living with HIV

Women living with HIV have fertility desires and intentions that are similar to those of uninfected women, and with advances in treatment most women can realistically plan to have and raise children to adulthood. Although HIV may have adverse effects on fertility, recent studies suggest that antiretroviral therapy may increase or restore fertility. Data indicate the increasing numbers of women living with HIV who are becoming pregnant, and that many pregnancies are unintended and contraception is underutilized, reflecting an unmet need for preconception care (PCC). In addition to the PCC appropriate for all women of reproductive age, women living with HIV require comprehensive, specialized care that addresses their unique needs. The goals of PCC for women living with HIV are to prevent unintended pregnancy, optimize maternal health prior to pregnancy, improve maternal and fetal outcomes in pregnancy, prevent perinatal HIV transmission, and prevent HIV transmission to an HIV-uninfected sexual partner when trying to conceive. This paper discusses the rationale for preconception counseling and care in the setting of HIV and reviews current literature relevant to the content and considerations in providing PCC for women living with HIV, with a primary focus on well-resourced settings.

Pre-Exposure Prophylaxis (PrEP) for Safer Conception Among Serodifferent Couples: Findings from Healthcare Providers Serving Patients with HIV in Seven US Cities

Pre-exposure prophylaxis (PrEP) can reduce the risk of HIV transmission among serodifferent couples trying to conceive, yet provider knowledge, attitudes, and experience utilizing PrEP for this purpose are largely unexamined. Trained interviewers conducted phone interviews with healthcare providers treating patients with HIV in seven cities (Atlanta, Baltimore, Houston, Kansas City, Newark, Philadelphia, and San Francisco, N = 85 total). Quantitative and qualitative data were analyzed to describe experience, concerns, and perceived barriers to prescribing PrEP for safer conception. Providers (67.1% female, 43 mean years of age, 70.4% white, 10 mean years treating HIV+ patients, 56% in academic vs. community facilities, 62.2% MD) discussed both benefits and concerns of PrEP for safer conception among serodifferent couples. Only 18.8% of providers reported experience prescribing PrEP, 74.2% were willing to prescribe it under ideal circumstances, and 7.0% were not comfortable prescribing PrEP. Benefits included added protection and a greater sense of control for the HIV-negative partner. Concerns were categorized as clinical, system-level, cost, or behavioral. Significant differences in provider characteristics existed across sites, but experience with PrEP for safer conception did not, p = 0.14. Despite limited experience, most providers were open to recommending PrEP for safer conception as long as patients understood the range of concerns and could make informed decisions. Strategies to identify and link serodifferent couples to PrEP services and clinical guidance specific to PrEP for safer conception are needed.

Building social networks for health promotion: Shout-out Health, New Jersey, 2011.

Background Building social networks for health promotion in high-poverty areas may reduce health disparities. Community involvement provides a mechanism to reach at-risk people with culturally tailored health information. Shout-out Health was a feasibility project to provide opportunity and support for women at risk for or living with human immunodeficiency virus infection to carry out health promotion within their informal social networks. Community Context The Shout-out Health project was designed by an academic–community agency team. During 3 months, health promotion topics were chosen, developed, and delivered to community members within informal social networks by participants living in Paterson and Jersey City, New Jersey. Methods We recruited women from our community agency partner’s clients; 57 women participated in in-person or online meetings facilitated by our team. The participants identified and developed the health topics, and we discussed each topic and checked it for message accuracy before the participants provided health promotion within their informal social networks. The primary outcome for evaluating feasibility included the women’s feedback about their experiences and the number of times they provided health promotion in the community. Other data collection included participant questionnaires and community-recipient evaluations. Outcome More than half of the participants reported substantial life challenges, such as unemployment and housing problems, yet with technical support and a modest stipend, women in both groups successfully provided health promotion to 5,861 people within their informal social networks. Interpretation Shout-out Health was feasible and has implications for building social networks to disseminate health information and reduce health disparities in communities.