Living through a pandemic: depression and anxiety experienced by youth living with HIV in South Africa.

Youth living with HIV (YLHIV) face significant psychosocial challenges and are at increasedrisk of developing depression and anxiety. This study aims to invesBgate symptoms ofdepression, anxiety and associaBons with psychosocial factors in YLHIV during the first andthird waves of the COVID-19 pandemic. This longitudinal study enrolled 135 YLHIV (ages 12-21) in Cape Town, South Africa. Measures administered telephonically included theCoRonavIruS Health Impact Survey (CRISIS quesBonnaire), Center for Epidemiologic StudiesDepression Scale (CES-D), Beck Anxiety Inventory and Beck Youth Inventory. During the firstwave of COVID-19, 7.5% and 8.0% of YLHIV were depressed (<18 and ≥18 years,respecBvely), and 10% and 4% of parBcipants were anxious (<18 and ≥18 years). During thethird wave, 8.9% and 40.6% of YLHIV were depressed (<18 and ≥18 years), and 13.3% and12.5% (<18 and ≥18 years) were anxious. Depression and anxiety were measured using cutoffscores provided by clinical measures. Symptoms of depression and anxiety in YLHIVescalated over the course of the COVID-19 pandemic. Socio-economic factors, substanceuse, disrupted support and stability concerns were associated with depression and anxiety.These data highlight the increasing need of mental health support and social intervenBonsfor YLHIV in post-pandemic South Africa.

Persistent accelerated epigenetic ageing in a longitudinal cohort of vertically infected HIV-positive adolescents.

We have previously shown accelerated ageing in adolescents perinatally infected with HIV (PHIV +), based on discrepancies between epigenetic and chronological age. The current study examines follow-up longitudinal patterns of epigenetic ageing and the association of epigenetic ageing with cognition as well as whole brain structure changes in PHIV + and healthy controls enrolled in the Cape Town Adolescent Antiretroviral Cohort Study (CTAAC). The Illumina EPIC array was used to generate blood DNA methylation data from 60 PHIV + adolescents and 36 age-matched controls aged 9-12 years old at baseline and again at a 36-month follow-up. Epigenetic clock software estimated two measures of epigenetic age acceleration: extrinsic epigenetic accelerated ageing (EEAA) and age acceleration difference (AAD) at both time points. At follow-up, each participant completed neuropsychological testing, structural magnetic resonance imaging, and diffusion tensor imaging. At follow-up, PHIV infection remains associated with increased EEAA and AAD. Accelerated epigenetic ageing remained positively associated with viral load and negatively associated with CD4 ratio. EEAA was positively associated with whole brain grey matter volume and alterations in whole brain white matter integrity. AAD and EEAA were not associated with cognitive function within the PHIV + group. Measures of epigenetic ageing, as detected in DNA methylation patterns, remain increased in PHIV + adolescents across a 36-month period. Associations between epigenetic ageing measures, viral biomarkers, and alterations in brain micro- and macrostructure also persist at 36-month follow-up. Further study should determine if epigenetic age acceleration is associated with cognitive functional changes due to brain alterations in later life.

Accelerated epigenetic aging in adolescents living with HIV is associated with altered development of brain structures.

We recently demonstrated that adolescents perinatally infected with HIV-1 (PHIV+) have accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock. However, whether epigenetic age acceleration in PHIV+ impacts brain development at the macro- and microstructural levels of brain anatomy has not been studied. We report on a cross-sectional study of PHIV+ enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC). The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 180 PHIV+ aged 9 to 12 years. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration (AgeAccelerationResidual) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent T1 structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). In order to investigate the associations of chronological age, sex, epigenetic age acceleration and treatment variables (CNS penetration effectiveness score (CPE)) of antiretroviral regimen on brain structure in PHIV+, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, cortical surface area and DTI measures of white matter microstructural integrity. The mean DNAm age (16.01 years) of the participants was higher than their mean chronological age (10.77 years). Epigenetic age acceleration contributed more to regional alterations of brain volumes, cortical thickness, cortical surface areas and neuronal microstructure than chronological age, in a range of regions. CPE positively contributed to volume of the brain stem. Understanding the drivers of epigenetic age acceleration could lead to valuable insights into structural brain alterations, and the persistence of neurocognitive disorders in seen in PHIV+ .

Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group.

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

HIV-Related Stigma and Psychological Adjustment Among Perinatally HIV-Infected Youth in Cape Town, South Africa.

The effect of chronic HIV-infection on psychological adjustment, including the impact of HIV-related stigma in perinatally HIV-infected (PHIV+) youth across Africa is largely unknown. This study examined psychological adjustment and HIV-related stigma using the Strengths and Difficulties Questionnaire (SDQ) and a 10-item stigma questionnaire in a cohort of PHIV+ youth in Cape Town, South Africa. The relationships between SDQ scores, elevated viral load, and suboptimal antiretroviral therapy (ART) adherence were also explored. Among 473 PHIV+ youth (aged 9-14 years, on ART > 6 months at enrollment), higher perceived HIV-related stigma was associated with higher scores across all adolescent and caregiver-reported SDQ difficulty subscales. Higher socioeconomic status (SES) was associated with lower scores on adolescent self- and caregiver-reported hyperactivity subscales. Higher adolescent-reported prosocial scores were associated with lower odds of self-reported suboptimal ART adherence, and higher caregiver-reported conduct scores were associated with higher odds of elevated viral load. No associations were observed between perceived HIV-related stigma and treatment outcomes. These findings highlight the potentially detrimental impact of perceived stigma on psychological adjustment in PHIV+ youth. The use of psychosocial metrics and interventions aimed at reducing illness related stigma in PHIV+ youth is also considered.

The association between mental health and metabolic outcomes in youth living with perinatally acquired HIV in the Cape Town Adolescent Antiretroviral Cohort.

Youth living with perinatally acquired HIV (YLPHIV) have been found to have a range of mental disorders. Some adult HIV studies have linked mental health to adverse metabolic outcomes due to dysregulation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, but this association has not previously been explored in YLPHIV.We investigated the association of mental health measures with metabolic outcomes in YLPHIV and HIV-uninfected youth (HIV-U) and linear regression was used to assess the adjusted associations.Overall, 203 YLPHIV (median age = 10.7years; 52% female; mean duration on ART 8 years, 12% CD4 count <500 cells/µL, 18% viral load >50 copies/mL) and 44 HIV-U (median age = 10.3 years; 55% female) were enrolled. YLPHIV had higher median total cholesterol (4.2 vs 3.9 mmol/L, p = 0.049) and triglyceride (0.9 vs 0.7 mmol/L, p < 0.001) compared to HIV-U. We found higher percentage of poor functional competence (40% vs 25%, p = 0.02) and self-concept (23% vs 9%, p = 0.03) and higher depression (6% vs 2%, p < 0.01), anger (6% vs 2%, p = 0.04) and disruptive behaviour (4% vs 0%, p < 0.01) in YLPHIV as compared to HIV-U. Among YLPHIV, higher scores of anger were associated with higher total cholesterol and higher low-density lipoprotein (ß = 0.010, p = 0.041 and ß = 0.012, p = 0.048 respectively) and disruptive behaviour with higher low-density lipoprotein (ß = 0.010, p = 0.043) after adjusting for age, sex and BMIZ.This is the one of first study to investigate the association of mental health with metabolic outcomes among YLPHIV. The association of increased anger and disruptive behaviour with increased lipid concentration is a novel finding. Further longitudinal studies are needed to evaluate the causal relationships between mental health and metabolic outcomes.

Youth perinatal HIV-associated neurocognitive disorders: association with functional impairment.

HIV-associated functional impairment may cause cognitive impairment secondary to the viral infection, hence, associations between cognitive impairment and functional impairment in youth living with HIV are important to assess. We sought to determine whether cognitive impairment is associated with functional impairment and if it carries higher risk for also having functional impairment. We collected parent-rated information regarding youth functional impairment on four different measures and administered a cognitive battery to youth to determine cognitive impairment, 203 HIV-infected youth and 44 HIV-uninfected controls. Degree of cognitive impairment correlated strongly with decreased function: CBCL, r = -.17, p = .01; VABS2, r = -.28, p < .001; repeated-grades, r = .26, p < .001. Presence of cognitive impairment was associated with increased risk of functional impairment: 3.47 (CIS); 1.71 (CBCL); 2.17 (VABS2); 2.97 (repeated-grades). Repeated-grades strongly associated with cognitive impairment and functional impairment. We found strong associations between HIV-infected youth functional impairment on CBCL, VABS2 and repeated-grades with degree of cognitive impairment; and that when cognitive impairment was present youth had higher risk of experiencing functional impairment as well. Asking whether youth have repeated a grade at school could be a helpful screening question for assessing potential functional impairment and provide clinicians with an indication as to whether a further in-depth assessment is required.

Global Systematic Review of Common Mental Health Disorders in Adults Living with HIV.

PURPOSE OF THE REVIEW: By reviewing the most recent common mental health disorders (CMHD) studies in people living with HIV (PLWH) (2018-2020), this review discusses the prevalence of CMHD, factors associated with CMHD in PLWH, mental health in PLWH from vulnerable groups, the impact of CMHD on HIV disease progression and adherence to antiretroviral therapy and the efficacy of different treatment approaches. RECENT FINDINGS: After screening for eligibility 142 studies were included in the final systematic review. Only 27% of studies were conducted in Sub-Saharan Africa, which carries the highest burn of HIV disease globally. Despite the well-established increased risk of CMHD in PLWH, the current prevalence remains high, with studies reporting 28%-62% of PLWH having mental health symptoms. CONCLUSION: Despite the significant challenges that CMHDs present to successful HIV treatment, there are many mental health treatments and interventions which can improve outcomes in PLWH and opportunities to task-shift and integrate mental health care with HIV care.

Adolescent-Centered HIV Prevention: Perspectives on Acceptability of Oral Antiretroviral Pre-exposure Prophylaxis for Adolescents in a Global Priority Setting.

With oral antiretroviral pre-exposure prophylaxis (PrEP) rollout expanding to include adolescents in South Africa, research is needed to better understand perceptions of PrEP acceptability among adolescents and clinical service providers. We conducted an exploratory mixed-methods study among 57 adolescents, 16-17 years of age, living with and without HIV, and 25 clinical service providers in Cape Town, South Africa from 2015 to 2016. Cross-sectional survey and semi-structured qualitative interview data were used to explore (1) willingness to use PrEP and support partner PrEP use among adolescents living with and without HIV, (2) willingness to prescribe or support prescription of PrEP among service providers, and (3) perceptions of barriers and facilitators to PrEP implementation and interpretations of PrEP efficacy messaging for adolescent HIV prevention among all participants. Acceptability of PrEP among participants was high. Support for PrEP uptake was linked to messages that positively framed PrEP's protection potential (i.e., success- versus failure-framed messaging) among both adolescents and providers. Adolescents living without HIV endorsed high willingness to use PrEP and adolescents living with HIV endorsed high support for partner PrEP use. However, both groups noted that potential side effects, stigma, and PrEP's partial efficacy may hinder uptake. Clinical service providers endorsed PrEP for sexually active adolescents and shared stigma and efficacy concerns. Further, service providers expressed desire for adolescent-tailored training and integration of PrEP delivery into primary care and family planning services. Efforts to educate adolescents and service providers about PrEP should consider how message framing may influence acceptability. Community PrEP education and adolescent-friendly delivery should be prioritized to alleviate predicted PrEP stigma and facilitate uptake.

Neural correlates of maintenance working memory, as well as relevant structural qualities, are associated with earlier antiretroviral treatment initiation in vertically transmitted HIV.

There is evidence of HIV affecting cognitive functioning across age groups, with adult studies showing related deficits in frontostriatal and hippocampal regional activity. Additionally, delayed initiation of antiretroviral treatment (ART) has been associated with poorer cognitive outcomes in HIV-infected youth. Little is known, however, of the neural correlates underlying such cognitive deficits in youth populations. We investigated maintenance working memory-related brain activity in South African HIV-infected youth and controls, and the effect of ART initiation age on underlying structures. Sixty-four perinatally infected youth (ages 9-12) and 20 controls (ages 9-13) underwent functional magnetic resonance imaging (fMRI) while completing 1-back and 0-back blocks of the N-back task. At an uncorrected p value threshold of 0.001, the HIV-infected group showed decreased activation in the left superior temporal gyrus, pre- and postcentral gyri, insula, and putamen as well as bilateral hippocampus, and mid cingulum. The HIV patients with delayed ART initiation showed less activation during processing conditions in the mid cingulum; left inferior parietal gyrus; and right inferior frontal, bilateral thalamic, and superior temporal regions. When these regions were tested for structural differences, the mid cingulum and right inferior frontal gyrus, insula, and thalamus were found to have less cortical thickness, surface area, or volume in the group with delayed ART initiation. Regional differences between HIV-infected youth and controls noted in the N-back task are consistent with impairments in structures involved in maintenance working memory. These data support earlier ART initiation in perinatally infected individuals.

Accelerated epigenetic aging in adolescents from low-income households is associated with altered development of brain structures.

The relationship between cognitive performance, macro and microstructural brain anatomy and accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock in healthy adolescents has not been studied. Healthy adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study were studied cross sectionally. The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 44 adolescents aged 9 to 12 years old. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration residual (AAR) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent neurocognitive testing, T1 structural magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI). Correlation tests were run between the two epigenetic aging measures and 10 cognitive functioning domains, to assess for differences in cognitive performance as epigenetic aging increases. In order to investigate the associations of epigenetic age acceleration on brain structure, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, and cortical surface area, as well as DTI measures of white matter microstructural integrity. In addition to negatively affecting two cognitive domains, visual memory (p = .026) and visual spatial acuity (p = .02), epigenetic age acceleration was associated with alterations of brain volumes, cortical thickness, cortical surface areas and abnormalities in neuronal microstructure in a range of regions. Stress was a significant predictor (p = .029) of AAR. Understanding the drivers of epigenetic age acceleration in adolescents could lead to valuable insights into the development of neurocognitive impairment in adolescents.

Methods of deliberate self-harm in a tertiary hospital in South Africa.

BACKGROUND: Little is known about the methods of deliberate self-harm (DSH) in South Africa (SA), despite the importance of means restriction as a public health strategy to reduce the morbidity and mortality associated with self-harm. AIM: The aim of this study was to investigate the range of methods used in DSH and identify the socio-demographic and clinical factors associated with violent and non-violent methods of DSH among patients treated at a tertiary hospital in SA. SETTING: The study was conducted at an urban, tertiary level emergency department at Groote Schuur hospital in Cape Town, South Africa. METHOD: Data were collected from 238 consecutive DSH patients who presented for emergency department treatment at the hospital. Logistic regression models were used to explore the factors associated with violent and non-violent methods of DSH. RESULTS: Self-poisoning was the most common method of self-harm (80.3%). Prescription medication was the most common form of self-poison (57.6%), while a large number of patients used non-prescription paracetamol (40.9%). In the regression analysis, male gender, stating that the reason for DSH was to escape a situation and history of substance use were associated with violent method of DSH. CONCLUSION: Improved monitoring of prescription medications commonly used in DSH is integral to public health suicide prevention strategies in SA. This study underscores the need for substance use interventions in the healthcare setting.

Initiation of antiretroviral therapy after the critical neuronal developmental period of the second postnatal year affects white matter microstructure in adolescents living with HIV.

Rapid maturation of major white matter pathways occurs in the first 2 years of life, indicating a critical neuronal developmental period. The impact of initiating antiretroviral therapy (ART) in children perinatally infected with HIV-1, after the age of 2 years on neurocognitive functioning and white matter development in adolescence has not been studied. Forty-six adolescents who initiated ART during the first 2 years of life (< 2 years) and 79 adolescents who initiated ART after 2 years of age (> 2 years), with perinatally acquired HIV were enrolled in the Cape Town Adolescent Antiretroviral Cohort. Adolescents completed a comprehensive neurocognitive battery testing a number of cognitive domains. Diffusion tensor imaging (DTI) was done to determine fractional anisotropy (FA), mean diffusivity (MD), axial diffusion (AD), and radial diffusion (RD) in a region of interest analysis. Neurocognitive performance was similar between adolescents who initiated ART < 2 years or > 2 years. There was a trend towards attention (p = .07) and working memory (p = .05) being poorer in the group who initiated ART > 2 years. FA was lower in the > 2-year group in the superior corona radiata (p = .03), and the external capsule (p = .04). MD was higher in the > 2-year group in the cerebral peduncle (p = .02), the superior corona radiata (p = .01), and the superior fronto-occipital fasciculus (p = .03). RD was higher in the > 2-year group in the superior corona radiata (p = .02), the cerebral peduncle (p = .01), and the superior fronto-occipital fasciculus (p = .01). However, the higher AD in the > 2-year group in the superior corona radiata was not in the expected direction (p = .01). Initiation of ART after the neuronal development period of the second postnatal year is associated with white matter alterations on neuroimaging.

Efavirenz is associated with altered fronto-striatal function in HIV+ adolescents.

Neurotoxicity associated with the antiretroviral efavirenz (EFV) has been documented in HIV-infected adults, but there are no data on the impact of EFV on brain function in adolescents. We investigated potential alterations in fronto-striatal function associated with EFV use in adolescents. A total of 86 adolescents underwent a Stop Signal Anticipation Task (SSAT) during functional MRI (fMRI), 39 HIV+ adolescents receiving EFV, 27 HIV+ adolescents on antiretroviral therapy without EFV (matched on age, gender, education, CD4 cell count and HIV viral load) and 20 HIV- matched controls (matched on age and gender). The task required participants to give timed GO responses with occasional STOP signals at fixed probabilities. Reactive inhibition was modelled as a correct STOP response and proactive inhibition was modelled after response slowing as the STOP probability increases. A priori mask-based regions associated with reactive and proactive inhibition were entered into two respective multivariate ANOVAs. The EFV treatment group showed significantly blunted proactive inhibitory behavioural responses compared to HIV+ adolescents not receiving EFV. There was no difference in reactive inhibition between treatment groups. We also demonstrated a significant effect of EFV treatment on BOLD signal in proactive inhibition regions. There was no difference in regions involved in reactive inhibition. We found no differences between adolescents not receiving EFV and HIV- controls, showing that functional and behavioural differences were unique to the EFV group. Here, we demonstrate for the first time a potential adverse impact of EFV on higher cortical function in young HIV+ adolescents.

Behavioural health risks during early adolescence among perinatally HIV-infected South African adolescents and same-age, HIV-uninfected peers.

Behavioural health risks, including substance use, early sexual debut, bullying and suicidality, are common during adolescence, but may be complicated among perinatally HIV-infected adolescents. However, there are few data exploring these behaviours in sub-Saharan Africa. We compared behavioural health risks (any self-report of substance use, sexual activity, bullying others or suicidality, or a positive urine toxicology screen) among perinatally-infected adolescents ages 9-14 years to that of an HIV-uninfected comparator group; and explored the effect of behavioural health risks on adolescent and caregiver report of adolescent suboptimal adherence (missed antiretroviral therapy dose(s) on ≥1 day during the preceding 30 days) and elevated HIV viral load (≥50 and ≥1000 copies/mL in sensitivity analyses) in multivariable logistic regression models. Among 506 HIV-infected and 110 HIV-uninfected adolescents (median age overall: 12 years), 15% and 25% reported any behavioural health risk (p = 0.018), respectively. Tobacco and other drug use was uncommon, while alcohol use was reported by 8% of HIV-infected versus 12% of HIV-uninfected adolescents (p = 0.185). One HIV-infected (0.2%) and 3 HIV-uninfected adolescents (3%) reported any sexual activity (p = 0.019). Among HIV-infected adolescents, report of any behavioural health risk was more common among male adolescents [adjusted odds ratio (aOR): 1.78; 95% confidence interval (CI): 1.08-2.95] and was associated with adolescent report of suboptimal adherence (aOR: 1.66; 95% CI: 0.99-2.78) but not with caregiver report of suboptimal adherence or with elevated viral load. In this group of perinatally-infected youth entering early adolescence, the prevalence of behavioural health risks was lower than that among same-age, HIV-uninfected peers. Longitudinal data are needed to explore the reasons underlying these differences, for example the possibility of more protective caregiving and supportive family environments, or of emotional and physical immaturity, as well as the emergence of risk behaviours over time in this population.

Association of Adolescent- and Caregiver-Reported Antiretroviral Therapy Adherence with HIV Viral Load Among Perinatally-infected South African Adolescents.

Accurate measurement of antiretroviral therapy (ART) adherence remains challenging and there are few data assessing the validity of self-reported adherence among perinatally HIV-infected adolescents. We examined adolescent and caregiver reports of adolescent adherence among perinatally-infected adolescents aged 9-14 years in Cape Town, South Africa, and explored factors that may modify associations between reported adherence and elevated viral load (VL). Among 474 adolescents (median age 12.0 years; median duration of ART use 7.5 years), elevated VL and caregiver- and adolescent-report of missed ART doses were common. Elevated VL was particularly prevalent among older, male adolescents. Low-moderate concordance was observed between caregiver and adolescent report. Among adolescents aged ≥ 12 years, caregiver- and adolescent-reported adherence was associated with elevated VL across most items assessed, but few significant associations were observed among adolescents < 12 years of age. Refined adherence measures and tools to identify adolescents who require adherence interventions are needed in this context.

HIV-associated cognitive disorders in perinatally infected children and adolescents: a novel composite cognitive domains score.

Accurate assessment of HIV-associated cognitive disorders in perinatally infected children and adolescents is challenging. Assessments of general intellectual functioning, or global cognition, may not provide information regarding domain-specific strengths and weaknesses, and may therefore fail to detect, impaired trajectories of development within particular cognitive domains. We compare the efficacy of global cognitive scores to that of composite cognitive domain scores in detecting cognitive disorders in a sample of perinatally HIV-infected children, and a demographically matched HIV negative control group, drawn from the Cape Town Adolescent Antiretroviral Cohort (CTAAC) study. All children were administered a comprehensive neuropsychological test battery. Using data from that test battery, we created ten separate composite cognitive domains: general intellectual functioning, attention, working memory, visual memory, verbal memory, language, visual spatial ability, motor coordination, processing speed and executive function. Within each domain, each test bore a high level of association with each of the other tests in that domain (Cronbach's α ≥ .70 for all domains). We found that composite domain scores calculated on whole-sample data were significantly higher than those calculated using control-sample data. Our comparison of a global cognitive score to composite domain scores suggested that the latter provided more detailed information (regarding strengths, weaknesses, areas of impairment), and when compared to global scores, were more sensitive in detecting HIV-associated cognitive disorders, and were able to distinguish HIV-infected patients from uninfected controls. Hence, we recommend using this method of composite cognitive domains scores, rather than global aggregate scores, when assessing cognitive function in paediatric HIV. This method provides a convenient and relatively accurate assessment that might help with cross-cultural and cross-region comparisons as researchers try to detect cognitive impairment patterns in HIV-infected children and adolescents globally.

Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity.

Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV- controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV- controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.

Mental health predictors of breastfeeding initiation and continuation among HIV infected and uninfected women in a South African birth cohort study.

Breastfeeding is a cost-effective, yet underutilized strategy to promote maternal and infant health in low and middle income countries (LMICs). Breastfeeding remains challenging for mothers living with HIV in LMICs, yet few studies have examined mental health predictors of breastfeeding initiation and continuation. We investigated breastfeeding among mothers by HIV status in South Africa, evaluating predictors of breastfeeding initiation and continuation to identify intervention-targets. Breastfeeding patterns were investigated in a subsample of 899 breastfeeding mothers from the Drakenstein Child Health Study; a prospective birth cohort of 1225 pregnant women, between March 2012 and March 2015 in a peri-urban area. Breastfeeding was assessed at 5 time-points between 6weeks and 24months' infant age. Cox proportional hazard models evaluated breastfeeding initiation and duration. Logistic regression models with breastfeeding non-initiation as the outcome parameter were performed to determine associations with maternal sociodemographic, psychosocial factors and gestational outcomes. More HIV-uninfected mothers initiated breastfeeding (n=685, 97%) than HIV-infected mothers (n=87, 45%). Median duration of exclusive breastfeeding was short (2months), but HIV-infected mothers engaged in exclusive breastfeeding for longer duration than uninfected mothers (3 vs 2months). Despite concerning high rates, mental disorders were not significant predictors of breastfeeding behaviour. Employment and HIV diagnosis during pregnancy predicted a lower likelihood of breastfeeding initiation among HIV-infected mothers, while employment was associated with earlier breastfeeding-discontinuation in HIV-uninfected mothers. Findings indicate that future interventions should target sub-populations such as HIV-infected women because of distinct needs. Workplace interventions appear particularly key for mothers in our study.

Correlates of emotional and behavioural problems in children with perinatally acquired HIV in Cape Town, South Africa.

In the antiretroviral era, youth perinatally infected with HIV (PHIV+) are surviving into adulthood and are at risk for emotional and behavioural problems. Few studies of these problems have been conducted in low- and middle-income countries and even fewer in sub-Saharan Africa. The aims of this study were to provide a quantitative description of emotional and behavioural problems in a group of PHIV+ youth (n = 78) in South Africa compared with a group of demographically matched HIV-negative controls (n = 30) and to identify correlates of emotional and behavioural problems. A cross-sectional study was conducted employing participants from community and hospital-based clinics. Emotional and behavioural problems were assessed using the Child Behaviour Checklist (CBCL). Several measures were used to assess demographic, biological, cognitive and contextual correlates of problem behaviours. Youth were compared by HIV status on demographic, cognitive and contextual variables as well as the Total Problems and subscale scores of the CBCL. Multivariate comparisons of the influence of contextual and cognitive variables on CBCL Total Problems scores were performed using a stepwise linear regression analytic procedure. In this study, there were no significant differences in between-group comparisons for the prevalence of Internalizing, Externalizing and Total Problems in the PHIV+ youth and control group at the clinical and borderline cut-off ranges of the CBCL. Caregiver depression was the only significant predictor of greater Total Problems scores in the full model, after controlling for age and gender (F = 8.57, df = 5.102, P < .01). An interaction between HIV status and caregiver depression was observed (t = -2.20, P = .03), with follow-up within-group analyses confirming that caregiver depression predicted greater Total Problems scores both in HIV-negative youth (ß = 0.61, P < .001), and to a lesser extent, in HIV-positive youth (ß = 0.25, P < .001). This study highlights the need for adequate screening of depression in the caregivers of HIV-infected youth.