No abstract

Significant cognitive deficits were documented among HIV+ children at school age, even when started on ART at an early age. Earlier HIV treatment, neuropsychological monitoring, and rehabilitative interventions are all needed. Subsequent testing for 2 more years will help further evaluate how HIV infection and exposure affect the developmental trajectory.

Objective: To compare growth among antiretroviral drug and maternal HIV-exposed uninfected (AHEU) versus age-matched and sex-matched HIV-unexposed uninfected (HUU) children. Design: Prospective cohort of AHEU children identified from the PROMISE trial (NCT01061151: clinicaltrials.gov registry) and age-matched and sex-matched HUU controls from child-wellness clinics, enrolled (September 2013 to October 2014) in Malawi and Uganda. Methods: Weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ), and head-circumference-for-age (HCAZ) z-scores were derived at 12 months and 24 months of age. Wilcoxon Rank-Sum and Fisher's exact tests were used for unadjusted exposure group comparisons. Generalized Estimating Equations models estimated adjusted relative risks (aRR) for poor growth outcomes. Results: Overall, 471 (50.5%) AHEU and 462 (49.5%) HUU children were assessed. Ugandan AHEU compared with HUU children had significantly lower mean LAZ (P < 0.001) and WAZ (P < 0.001) at 12 and 24 months of age and HCAZ (P = 0.016) at 24 months, with similar but not significant differences among Malawian AHEU and HUU children. The risk of stunting (more than two standard deviations below the WHO population LAZ median) was increased among AHEU versus HUU children: aRR = 2.13 (95% confidence interval (CI): 1.36–3.33), P = 0.001 at 12 months, and aRR = 1.67 (95% CI 1.16–2.41), P = 0.006 at 24 months of age in Uganda; and aRR = 1.32 (95% CI 1.10–1.66), P = 0.018, at 24 months of age in Malawi. The risk of HCAZ below WHO median was increased among AHEU versus HUU children at 24 months of age, aRR = 1.35 (95% CI 1.02–1.79), P = 0.038 in Uganda; and aRR = 1.35 (95% CI 0.91–2.02), P = 0.139 in Malawi. Conclusion: Perinatal exposures to maternal HIV and antiretroviral drugs were associated with lower LAZ (including stunting), WAZ and HCAZ at 24 months of age compared with HUU children.

Children affected by HIV are at increased risk of developmental and neuropsychological disturbances due to direct effects of HIV on the brain and direct effects associated with living in poverty. Caregivers can play an important role, through quality caregiving, in mitigating the negative effect of these stressors. This study used baseline data from an ongoing caregiver training intervention trial to evaluate the association between quality of caregiver–child interactions and neurocognitive outcomes in rural HIV-infected and HIV-exposed but uninfected children in Uganda. We also assessed the extent to which caregiver distress moderated this relationship. Data on 329 caregiver–child dyads were collected between March 2012 and July 2014, when the children were between 2 and 5 years of age. Child outcomes include the Mullen Scales of Early Learning to assess general cognitive ability and the Color Object Association Test to assess immediate memory and total recall. Caregiving quality was assessed using the Home Observation for the Measurement of the Environment (HOME) total and subscale scores. Caregiver distress was assessed using the Hopkins Symptom Checklist. General linear regression models assessed the association between the HOME total and subscale scores and child outcomes, with interaction terms used to test moderation by caregiver distress. Total HOME scores were positively and significantly associated with Mullen scores of cognitive ability; HOME acceptance subscale scores were positively and significantly associated with immediate recall scores. No other associations were statistically significant. As hypothesized, there is a strong association between the HOME and Mullen scores of cognitive ability in our study population, such that children who were assessed as living in environments with more stimulation also presented with a higher level of general neurocognitive development. Our results support the view of program guidance for HIV-affected children that suggest family-oriented care with emphasis on parent–child relationships for optimal child development.

Objective Early childhood development (ECD) programs typically combine healthy nutrition and cognitive stimulation in an integrated model. We separately delivered these two components in a cluster randomized controlled trial (RCT) to evaluate their comparative effectiveness in promoting healthy child development and caregiver mental health. This is the first study to do so for HIV-affected children and their infected mothers,. Methods 221 HIV-exposed but uninfected (HEU) child (2 to 3 years old) and caregiver dyads in 18 geographic clusters in Eastern Uganda were randomized by cluster to receive biweekly individualized sessions of either 1) Mediational Intervention for Sensitizing Caregivers (MISC) training emphasizing cognitive stimulation, or 2) Uganda Community Based Association for Child Welfare program that delivered (UCOBAC) health and nutrition training. Children were evaluated at baseline, six months, one year (training conclusion), and one-year post-training with the Mullen Scales of Early Learning (MSEL), the Color-Object Association Test (COAT) for memory, the Early Childhood Vigilance Test (ECVT) of attention, and the Behavior Rating Inventory of Executive Function (BRIEF-parent). The Caldwell HOME was completed by observers to gauge caregiving quality after training. Caregiver depression/anxiety (Hopkins Symptom Checklist-25) and functionality (list of activities of daily living) were also evaluated. Data collectors were blinded to trial arm assignment. Results MISC resulted in significantly better quality of caregiving compared to UCOBAC mid-intervention with an adjusted mean difference (MadjDiff ) of 2.34 (95% CI: 1.54, 3.15, p<0.01), post intervention (MadjDiff=2.43, 95% CI: 1.61, 3.25, p<0.01) and at one year follow-up (MadjDiff=2.07, 95% CI: 1.23, 2.90, p<0.01). MISC caregivers reported more problems on the BRIEF for their child at one-year post-training only (p<0.01). Caregiving quality (HOME) was significantly correlated with MSEL composite performance one-year post training for both the MISC and the UCOBAC trial arms. Likewise, physical growth was significantly related to child development outcomes even though it did not differ between trial arms. Conclusions Even though MISC demonstrated an advantage of improving caregiving quality, it did not produce better child cognitive outcomes compared to health and nutrition training.

BackgroundKabul has over 12,000 people who inject drugs (PWID), most of them heroin users, and opioid substitution therapy has recently been introduced as an effective method to reduce opioid use. We aimed to evaluate a pilot Opioid Substitution Therapy Pilot Program (OSTPP) in Kabul, Afghanistan, particularly to (1) describe characteristics of the participants enrolled in the program and (2) identify factors associated with client retention in the OSTPP.FindingsTwo cross-sectional surveys evaluated participants attending the OSTPP at baseline (n = 83) and 18 months after (n = 57). Questionnaires assessed socio-demographic, drug use behavior, and general and mental health factors. After 18 months, 57 participants remained in the OSTPP. Participants lost to follow-up were younger (p < 0.01) and married (p < 0.01) and had no family contact (p < 0.01). Participants at 18 months reported no criminal activity in the last month and only two (3.5 %) reported heroin use in the last month, constituting significant decreases from baseline.ConclusionsWhile preliminary results are promising, further evaluation is needed to determine the feasibility of implementing OSTPP in this setting and effectiveness in reducing injection risk behaviors in Afghanistan.

Background Children living with human immunodeficiency virus (HIV) are at neuropsychological risk for cognitive and motor dysfunction. However, few prospective, multi-site studies have evaluated neuropsychological outcomes longitudinally among perinatally infected African children who received early antiretroviral treatment (ART). Methods We enrolled 611 children aged 5 to 11 years at 6 sites (South Africa [3], Zimbabwe, Malawi, Uganda). Of these, there were 246 children living with HIV (HIV+) who were initiated on ART before 3 years of age in a prior clinical trial comparing nevirapine to lopinavir/ritonavir (International Maternal Pediatric Adolescent Acquired Immunodeficiency Syndrome Clinical Trials [IMPAACT] P1060); 183 age-matched, exposed but uninfected (HEU) children; and 182 unexposed and uninfected (HUU) children. They were compared across 3 assessment time points (Weeks 0, 48, and 96) on cognitive ability (Kaufman Assessment Battery for Children, second edition [KABC-II]), attention/impulsivity (Tests of Variables of Attention [TOVA]), motor proficiency (Bruininks-Oseretsky Test, second edition [BOT-2]), and on the Behavior Rating Inventory of Executive Function (BRIEF). The cohorts were compared using linear mixed models, adjusting for site, child’s age and sex, and selected personal/family control variables. Results The HIV+ cohort performed significantly worse than the HEU and HUU cohorts for all KABC-II, TOVA, and BOT-2 performance outcomes across all 3 time points (P values &lt; .001). The HUU and HEU cohorts were comparable. For the KABC-II planning/reasoning subtests, the HIV+ children showed less improvement over time than the HUU and HEU groups. The groups did not differ significantly on the BRIEF. Conclusions Despite initiation of ART in early childhood and good viral suppression at the time of enrollment, the HIV+ group had poorer neuropsychological performance over time, with the gap progressively worsening in planning/reasoning. This can be debilitating for self-management in adolescence.

There is growing concern that although the more severe forms of HIV associated neurologic deficits are reduced following highly active anti-retroviral therapy (HAART), mild to moderate cognitive disorders may persist for years after HAART initiation and this may occur despite complete plasma viral suppression. According to the UNAIDS 2014 report, there were 3.2 million children living with HIV around the world at the end of 2013 and 91% of these resided in sub-Sahara Africa. In the same year only 24% of children who needed antiretroviral treatment (ART) received it and 190,000 children died of AIDS-related illnesses. We propose that behavioral interventions are needed in combination with medical treatment and care in order to fully address the needs of children and adolescents in Africa living with HIV. In early childhood, caregiver training programs to enhance the developmental milieu of the child with HIV can enhance their cognitive and social development, and that such interventions are both feasible and well-accepted by the local population. For school-age children, computerized cognitive rehabilitation training can be an entertaining and engaging way to improve attention, working memory, and problem solving skills for children with HIV. Further dissemination and implementation science work is needed for arriving at cost effective strategies for scaling up such behavioral interventions in African resource-constrained settings, given that the vast majority of HIV-affected children and youth worldwide presently live in sub-Sahara Africa.