Measuring ART Adherence Among Young Adults with Perinatally Acquired HIV: Comparison Between Self-report, Telephone-Based Pill Count, and Objective Pharmacologic Measures.

Tenofovir diphosphate (TVF-DP) can be quantified in red blood cells (RBCs) and dried blood spots (DBS) and can objectively measure ART adherence and predict viral suppression. Data on the association of TFV-DP with viral load are very limited in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV), as are data comparing TFV-DP to other measures of ART adherence, such as self-report and unannounced telephone pill count. Viral load and ART adherence (self-report, TFV-DP and unannounced telephone pill count) were assessed and compared among 61 AYAPHIV recruited from an ongoing longitudinal study (CASAH) in New York City.

Construct Validity Supports Use of a Novel, Tablet-Based Neurocognitive Assessment for Adolescents and Young Adults Affected by Perinatal HIV from Vulnerable Communities in the United States.

Construct validity of novel tablet-based neurocognitive tests (in the NeuroScreen app) measuring processing speed, working memory, and executive functioning in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV) and perinatal HIV-exposure without infection (PHEU) was examined. Sixty-two AYA (33 PHIV, 29 PHEU) were recruited from an ongoing longitudinal study (CASAH) in New York City. Medium to large and statistically significant correlations were found between NeuroScreen and gold standard, paper-and-pencil tests of processing speed, working memory, and executive functioning. Results provide partial support for NeuroScreen as an alternative to cumbersome paper-and-pencil tests for assessing neurocognition among HIV-affected AYA.

Longitudinal trajectories of neurocognitive test performance among individuals with perinatal HIV-infection and -exposure: adolescence through young adulthood.

There are an estimated 2.1 million youth less than 15 years of age living with HIV globally (the majority perinatally HIV-infected [PHIV]) and millions more perinatally HIV-exposed uninfected (PHEU) youth who are expected to survive through adolescence and into adulthood. Transitioning from adolescence to young adulthood requires adaptation to more demanding social interactions, academic pressures, and individual responsibilities which place distinct demands on neurocognitive functions. This study examined longitudinal trajectories of neurocognitive test performance in the domains of processing speed (PS), working memory (WM), and executive functioning (EF) among PHIV and demographically similar PHEU from adolescence through young adulthood. Data for this paper come from four time points, spanning approximately 10 years, within the Child and Adolescent Self-Awareness and Health Study (CASAH). Youth age ranged from 15 to 29 years. Longitudinal linear mixed effect models were computed for each test. Few differences in performance were found on tests of EF and WM between PHIV and PHEU youth as they aged, though PHEU youth showed significantly better PS as they aged than PHIV youth. Future research is needed to understand these vulnerable youth's neurocognitive trajectories as a function of HIV infection and -exposure, biological functions and psychosocial stressors.

Association of anthropometric status and residential locality factors with cognitive scores of 4-6-year-old children in Kwazulu-Natal, South Africa.

Background: The Asenze study has the long-term goal of promoting better physical, cognitive and psychosocial functioning of children in a rural area in KwaZulu-Natal, 50 km from Durban with a view to planning interventions to promote growth and development for very young children. The specific objective in this paper was to provide information for the Child Health and Development project of the Valley Trust to assist with intervention planning. The broader goal was to assess developmental delays in communities ravaged by the HIV epidemic.The Asenze study was designed in two phases from 2008 and 2012. The current paper reports on 1581 4-6years old children in the baseline phase (2008-2010) in the five adjacent tribal areas in the study area. Method: The participants included all the 4 - 6 year olds whose parents had consented to inclusion in the project and their caregivers. Data were derived from a brief questionnaire administered in the homes of participants, and subsequently from medical and psychological assessments of the children and their caregivers at the Asenze clinic. The association between child factors and other factors (geographic area, socioeconomic status (SES), parental level of education, the child's pre-school education) on the one hand and, the child's cognitive performance (as measured by the Grover Counter and subtests of the KABC-11) were analysed. Linear regression models were employed to determine which predictor variables of interest in a model were associated with the children's cognitive scores as the dependent variables. Results: Based on the data, the principal factors associated with children's cognitive outcomes were height-for-age z-score (HAZ), preschool education and the area of residence, Generally children who had low cognitive scores were more often stunted (as defined by the WHO anthropometric tables), had not had pre-school education, and came from areas less favourable in terms of local infrastructure and access to employment opportunities and arable land. Conclusion: The finding from this cross-sectional analysis of baseline data showed that in addition to height for age and pre-school education, which are commonly thought to impact on cognition, the local authority area where the children lived was associated with their scores on cognitive tests. This has implications for intervention planning. The functioning of local government in promoting the type of community development which will protect the rights of children should be taken into account.

Empowering Lay-Counsellors with Technology: Masivukeni, a Standardized Multimedia Counselling Support Tool to Deliver ART Counselling.

Lay-counsellors in resource-limited settings convey critical HIV- and ART-information, and face challenges including limited training and variable application of counselling. This study explored lay-counsellors and Department of Health (DoH) perspectives on the utility of a multimedia adherence counselling program. Masivukeni, an mHealth application that provides scaffolding for delivering standardized ART counselling was used in a 3-year randomized control trail at two primary health care clinics in Cape Town, South Africa. In this programmatic and descriptive narrative report, we describe the application; lay-counsellors' response to open-ended questions regarding their experience with using Masivukeni; and perspectives of the City of Cape Town and Western Cape Government DoH, obtained through ongoing engagements and feedback sessions. Counsellors reported Masivukeni empowered them to provide high quality counselling. DoH indicated strong support for a future implementation study assessing feasibility for larger scale roll-out. Masivukeni has potential as a counselling tool in resource-limited settings.

Changes in Substance Use Symptoms Across Adolescence in Youth Perinatally Infected with HIV.

The paper utilizes data collected at three time points in a longitudinal study of perinatally HIV-infected (PHIV+) and a comparison group of perinatally exposed but HIV-uninfected (PHEU) youths in the United States (N = 325). Using growth curve modeling, the paper examines changes in substance use symptoms among PHIV+ and PHEU youths as they transition through adolescence, and assesses the individual and contextual factors associated with the rate of change in substance use symptoms. Findings indicate that substance use symptoms increased over time among PHIV+ youths, but not among PHEU youths. The rate of change in these symptoms was positively associated with an increasing number of negative life events. Study findings underscore the need for early, targeted interventions for PHIV+ youths, and interventions to reduce adversities and their deleterious effects in vulnerable populations.

An Exploration of Family and Juvenile Justice Systems to Reduce Youth HIV/STI Risk.

Using in-depth interviews with 20 probation youth (60% female; 35% white; 30% Hispanic; mean age 15years, range=13-17), their caregivers (100% female; mean age 44years, range=34-71) and 12 female probation officers (100% white; mean age 46years, range=34-57), we explored how family and probation systems exacerbate or mitigate sexual risk. We conducted thematic analyses of interviews, comparing narratives of families of sexually risky (n=9) versus non-sexually risky (n=11) youth. Family functioning differed by youth sexual risk behavior around quality of relationships, communication, and limit-setting and monitoring. The involvement of families of sexually risky youth in probation positively influenced family functioning. Data suggest these families are amenable to intervention and may benefit from family-based HIV/STI interventions delivered in tandem with probation.

HIV+ and HIV- youth living in group homes in South Africa need more psychosocial support.

Orphans and vulnerable youth who live in group homes are at risk of poor mental health and sexual and drug-using behaviors that increase the risk of HIV transmission. This study explores factors related to this risk among youth living in group homes ("children's homes") for orphans and vulnerable children in South Africa, a country afflicted by high levels of parental loss due to HIV. The study explores 1) knowledge and attitudes about HIV, 2) social support, 3) communication with group home caregivers, and 4) the relevance of an existing evidence-based HIV prevention and mental health promotion program to situations where sexual and drug risk behaviors can occur. In-depth qualitative individual interviews were conducted with 20 youth (age 10 to 16 years) residing in two children's homes in Durban, South Africa. Content analysis focused on critical themes related to coping and prevention of risk activities. Respondents exhibited inconsistent and incomplete knowledge of HIV transmission and prevention. They displayed positive attitudes toward people living with HIV, but reported experiencing or witnessing HIV-related stigma. Participants witnessed substance use and romantic/sexual relationships among their peers; few admitted to their own involvement. While relationships with childcare workers were central to their lives, youth reported communication barriers related to substance use, sex, HIV, and personal history (including parental loss, abuse, and other trauma). In conclusion, these qualitative data suggest that evidence-based HIV prevention programs that bring caregivers and youth together to improve communication, HIV knowledge, social support, youth self-esteem, and health care, reduce sexual and drug risk behaviors, and strengthen skills related to negotiating situations of sexual and substance use possibility could benefit youth and childcare workers in children's homes.

Psychosocial challenges and protective influences for socio-emotional coping of HIV+ adolescents in South Africa: a qualitative investigation.

INTRODUCTION: While the roll-out of antiretroviral therapy in South Africa should lead to a reduction in mother to child transmission, mortality and orphaning, it will also be accompanied by a large number of children entering adolescence and adulthood with a chronic infectious disease. Adolescence is a particularly vulnerable period for HIV-infected people in relation to mental health problems and engagement in high-risk behaviours, including non-compliance with medical treatment. The goal of this qualitative study was to develop an understanding of the psychosocial challenges as well as protective influences promoting socio-emotional coping in HIV+ adolescents in order to inform mental health promotion and HIV prevention programming for this population in South Africa. METHOD: In-depth qualitative interviews were conducted with HIV+ adolescents (25) and caregivers of HIV+ children (15) at a large HIV/AIDS Clinic in South Africa. Data were analysed thematically using NVivo8 software. RESULTS: Psycho-social challenges for adolescents included dealing with loss of biological parents in the case of orphans; coming to terms with their HIV+ status including identity difficulties; external stigma and discrimination; and disclosure difficulties. For caregivers, disclosure and lack of financial, family and social support emerged as key challenges. Medication, HIV information, a future orientation and social support was identified as important for coping and general well-being of adolescents, with financial and social support emerging as key for promoting supportive caregiving contexts. CONCLUSION: While HIV+ adolescents in South Africa experience similar concerns to those in high-income countries, socio-emotional coping may be compromised by increased levels of loss due to the late roll-out of ARVS and challenges to caregiving contexts including poverty, stigma and minimally supported foster care arrangements. There is a need for mental health promotion programmes for adolescents to adopt an ecological approach, strengthening protective influences at the individual, interpersonal, community and policy levels.

Power and empowerment: fostering effective collaboration in meeting the needs of orphans and vulnerable children.

In sub-Saharan Africa, HIV/AIDS has resulted in a rapidly growing population of orphans and vulnerable children (OVC). These OVC have strained the traditional safety net provided by extended families to its breaking point. Increasingly, community-based initiatives are emerging to fill the gap. However, relatively little is known about these efforts and their effectiveness. This article looks at one such initiative in rural Tanzania, and explores the relationship between local communities that seek to empower themselves to address the needs of their OVC and external organisations that have the resources and power to help them. This case study describes the successful effort of a community to build a Centre housing its orphans, and the subsequent closure of that Centre despite its evident success, because of a conflict between internal and external interests. This case study is used as the basis of a broader discussion on how those with power, and communities seeking empowerment, are complexly intertwined.

Adherence to antiretroviral treatment among pregnant and postpartum HIV-infected women.

Among women with HIV infection, pregnancy is a time when maintenance of maternal health and reduction of vertical HIV transmission are primary concerns. Few studies have examined adherence to Antiretroviral Treatment (ART) during pregnancy and in the postpartum period when the demands of childcare may significantly interfere with women's self-care behaviors. This study examined ART use and adherence in HIV-infected pregnant and postpartum women participating in the Women and Infants Transmission Study (WITS-IV) in the US. Adherence was assessed through a self-report interview during the third trimester of pregnancy and six-month postpartum. Data were also collected on demographics, biomedical markers and health related symptoms. During the third trimester visit, 77% (309/399) of women completed the self-report adherence measure; 61% (188/309) reported complete adherence. Factors associated with non-adherence included advanced HIV disease status, higher HIV-RNA viral load, more health-related symptoms and alcohol and tobacco use. At six-month postpartum, 55% (220/399) completed the measure; 44% (97/220) of these women reported complete adherence. Factors associated with non-adherence during the postpartum period were ethnicity, more health-related symptoms and WITS clinical site. Results of multivariate analyses using Generalized Estimated Equation analyses across the two visits revealed that more health-related symptoms, higher HIV-RNA viral load, increased alcohol use and clinical site were independently associated with ART non-adherence. These analyses indicate that medication adherence is more likely during pregnancy than postpartum in HIV-infected women, perhaps provoked by motivation to reduce vertical transmission and/or intensive antepartum surveillance. Further investigation is warranted to clarify factors implicated in women's decision-making process regarding ART medication adherence.

Adherence in people living with HIV/AIDS, mental illness, and chemical dependency: a review of the literature.

Adherence to antiretroviral medications is central to reducing morbidity and mortality among people living with HIV/AIDS. Relatively few studies published to date address HIV adherence among special populations. The purpose of this article is to review the existing literature on HIV antiretroviral adherence, with an emphasis on studies among the triply diagnosed population of people living with HIV/AIDS, mental illness, and chemical dependency. In order to reflect the most current information available, data from conference proceedings, federally funded studies in progress, and the academic literature are presented for consideration.

Head growth and neurodevelopment of infants born to HIV-1-infected drug-using women.

OBJECTIVE: To describe neurodevelopment and head growth in HIV-1-infected and exposed uninfected infants with and without in utero exposure to opiates and cocaine. METHODS: Using data from a multicenter cohort study of HIV-1-infected women and their children, the authors fit repeated measures regression models to estimate the effects of HIV-1 infection and in utero hard drug exposure on head circumference and Bayley Scales of Infant Development standard scores during the first 30 months. RESULTS: Of the 1,094 infants included in the analysis, 147 (13%) were HIV-1-positive and 383 (35%) were exposed in utero to opiates or cocaine (drug-positive). Mean 4- month Bayley mental scores were lower in infants with only HIV-1 positivity (HIV-positive and drug-negative) (-8.2 points, p < 0.0001) or only drug exposure (HIV-negative and drug-positive) (-4.4 points, p = 0.0001) and tended to be lower in infants with both factors (HIV-positive and drug-positive) (-3.7 points, p = 0.0596), compared with those who were HIV-1-negative and not drug exposed (HIV-negative and drug-negative). However, by 24 months of age, there was no longer a decrement among HIV-negative and drug-positive infants, whereas HIV-1 infection was still associated with a decrement relative to uninfected infants. Similar results were seen for Bayley motor scores and for head circumference Z scores. CONCLUSIONS: HIV-1 infection and in utero opiate and cocaine exposure decrease birth head circumference and slow neurodevelopment at 4 months. At 24 months of age, however, only HIV-1 infection is associated with decreased neurodevelopment and head circumference. There may be some postnatal recovery from the effects of in utero hard drug exposure. Importantly, the detrimental effects of HIV-1 positivity and maternal hard drug use on neurodevelopment at 4 months are not additive, although they are additive for birth head circumference.

Brief report: effects of pediatric HIV infection on mental and psychomotor development.

OBJECTIVE: To examine the effect of HIV status on infants' mental and psychomotor functioning, controlling for confounding factors such as prenatal drug exposure and birth conditions. METHODS: Twenty HIV-infected and 25 seroreverted infants (ages 3-30 months old) were administered the Bayley Scales of Infant Development (BSID) and a neurological examination at two time points, 4 to 12 months apart. The majority were from ethnic minority, socioeconomically disadvantaged families; 67% of the infants were prenatally drug-exposed. RESULTS: HIV-infected infants had significantly lower scores on the BSID at baseline (mental development) and follow-up (motor development) compared to seroreverters. When HIV and neurological deficits were considered together, HIV+ children with neurological deficits scored significantly lower than HIV+ children without neurological deficits and seroreverters, with and without neurological diagnoses. Prenatal drug exposure was not associated with performance on the BSID. CONCLUSIONS: These data suggest that CNS involvement is a critical pathway by which HIV affects infants' neurodevelopment.

Timing of perinatal human immunodeficiency virus type 1 infection and rate of neurodevelopment. The Women and Infant Transmission Study Group.

BACKGROUND: Identifying HIV-1-infected children who are at greatest risk for disease-related morbidities is critical for optimal therapeutic as well as preventive care. Several factors have been implicated in HIV-1 disease onset and severity, including maternal and infant host characteristics, viral phenotype and timing of HIV-1 infection. Early HIV-1 culture positivity, i.e. intrauterine infection, has been associated with poor immunologic, virologic and clinical outcomes in children of HIV-infected women. However, a direct effect of timing of infection on neurodevelopmental outcome in infancy has not yet been identified. METHODS: Serial neurodevelopmental assessments were performed with 114 infants vertically infected with HIV-1 in a multicenter natural history, longitudinal study. Median mental and motor scores were compared at three time points. Longitudinal regression analyses were used to evaluate the neurodevelopmental functioning of children with early positive cultures and those with late positive cultures. RESULTS: Early infected infants scored significantly lower than late infected infants by 24 months of age and beyond on both mental (P = 0.05) and motor (P = 0.03) measures. Early HIV-1 infection was associated with a decline in estimated motor scores of 1 standard score point per month compared with 0.28 point in the late infected group (P < 0.02). Estimated mental scores of the early infected group declined 0.72 point/ month, whereas the average decline of the late infected group was 0.30 point/month (P < 0.13). CONCLUSION: Early HIV-1 infection increases a child's risk for poor neurodevelopmental functioning within the first 30 months of life.

Children's methods of coping with stress: a twin study of genetic and environmental influences.

The relative importance of environmental and hereditary factors in how children cope with stress was examined. Emotion-focused, problem-focused, and additional coping variables were assessed in 44 monozygotic (MZ) and 30 dizygotic (DZ) twin pairs, aged 9-16 years. The effects of heritability, shared environment, and unshared environment were examined in structural modelling analyses. Genetic factors accounted for a majority of the reliable variance in four of seven coping variables, while effects of twins' shared environment were negligible for all but one coping variable. Environmental factors important to individual differences in coping strategies were primarily unique to each child (unshared between the twins), highlighting the importance of individual experiences in shaping coping behaviors.

Effects of pediatric HIV infection and prenatal drug exposure on mental and psychomotor development.

Examined the effects of HIV infection and prenatal drug exposure on infant neurodevelopmental functioning. Three groups of infants were compared: HIV-infected infants, seroreverters, and a comparison group who were prenatally exposed to drugs, but not HIV. Two thirds of the HIV-infected and seroreverter infants were prenatally drug-exposed. Infants (ages 4-30 months) were administered the Bayley Scales of Infant Development. Children who were both HIV-infected and prenatally drug exposed performed significantly lower on both the mental and psychomotor scales of the Bayley. Drug exposure and neurological dysfunction were associated with mental development, whereas neurological dysfunction, drug exposure, and HIV status were associated with psychomotor development.

Families affected by pediatric acquired immunodeficiency syndrome: sources of stress and coping.

This study explores stress and coping among inner-city, ethnically diverse families with human immunodeficiency virus (HIV)-infected children. Caregivers, siblings, and HIV-infected children from 25 families responded to a semistructured interview on the psychosocial impact of HIV. Families were primarily African-American and Latino and from low socioeconomic-status backgrounds. Approximately one third of the children lived with an HIV-positive birth parent, one third with a grandmother, and one third in foster or adoptive care. The majority of caregivers were single mothers who confronted major life events and who were overextended with caregiving responsibilities. Compared with uninfected caregivers, HIV-infected parents reported more isolation and fewer financial and support resources. All children were particularly vulnerable to separations and loss, with uninfected siblings reporting anger and burden from caregiving tasks. Although some families had coping resources, many families might benefit from family-focused mental health services, particularly those that reduce isolation, promote family functioning and provide respite care.

Cognitive assessment of human immunodeficiency virus-exposed children.

OBJECTIVE: To determine (1) the level of impairment in cognitive and motor functioning in human immunodeficiency virus (HIV)-exposed and HIV-infected preschool and school-age children; (2) cognitive strengths and weaknesses that characterize HIV-infected children; and (3) potential contributions of serostatus, neurologic impairment, and prenatal drug-exposure to cognitive functioning. DESIGN: Cross-sectional, single-blind study. SETTING: Pediatric neurology clinic at a large metropolitan hospital in New York, NY. PARTICIPANTS: Forty-one HIV-infected and eight seroreverter school-age children. INTERVENTIONS: The McCarthy Scales of Children's Abilities were administered to all children, as was the Neurologic Examination for Children. MEASUREMENTS/MAIN RESULTS: The obtained mean of the sample on the McCarthy Scales' General Cognitive Index was in the Borderline range, with 44% of the subjects scoring in the Mentally Retarded range. The most severe cognitive deficits were found on the Quantitative, Verbal, and Memory scales (Borderline range). Children infected with HIV with neurologic impairment performed significantly worse than did seroverters and neurologically normal HIV-infected children. There were no significant differences in cognitive functioning due to gender, ethnicity, and prenatal drug exposure. CONCLUSIONS: Cognitive deficits were detected in HIV-infected and seroreverted children. The presence of neurologic dysfunction in HIV-infected children markedly intensified these deficits.

Genetic and environmental influences on positive and negative affect: support for a two-factor theory.

Genetic and environmental etiologies of positive and negative affect, as measured by the Bradburn Affect Balance Scale, were studied to gain understanding of a two-factor theory of well-being. It was hypothesized that negative affect would demonstrate significant genetic and environmental variance and positive affect would be explained primarily by environmental influences. Data were combined from 105 pairs of twins (ages 18-72) and 220 multigenerational families (ages 16-98). Simultaneous model fitting indicated significant heritable effects for negative affect and a significant effect of common environment for twins. Significant effects for positive affect included common environment (for parents and offspring and for twin pairs) and assortative mating. These results, documenting differential genetic and environmental influences on positive and negative affect, provide further support for their being separate components of well-being.