Early Antiretroviral Therapy in HIV-Infected Children Is Associated with Diffuse White Matter Structural Abnormality and Corpus Callosum Sparing

BACKGROUND, PURPOSE: Fractional anisotropy in the frontal white matter, corpus callosum and internal capsule are abnormal in HIV+ adults. We describe the distribution, nature of white matter abnormalities in a cohort of children who started ART within the first year of life - and benefit of early treatment using DTI measures (fractional anisotropy, mean, axial and radial diffusion). MATERIALS, METHODS: DTI was performed on children in a neurodevelopmental sub study from the Children with HIV Early Antiretroviral (CHER) trial. Voxel-based group comparisons were performed to determine regions where fractional anisotropy and mean diffusion differed between HIV+ and uninfected children. Associations of DTI parameters with timing of ART initiation were examined. RESULTS: 39 HIV+ children (15 male, mean age 5.4 years) and 13 controls (5 male, mean age 5.7 years) were imaged. 2 Clusters with lower fractional anisotropy and 7 clusters with increased mean diffusion were identified in the HIV+ group with symmetrical distribution predominantly due to increased radial diffusion, suggestive of decreased myelination. Corticospinal tracts rather than the corpus callosum were predominantly involved. Children on early interrupted ART had lower fractional anisotropy compared to those receiving continuous treatment. CONCLUSION: HIV+ children at 5 years have white matter abnormalities measured by fractional anisotropy, despite early ART, suggesting that early ART does not fully protect the white matter either from peripartum or in utero infection. In contrast to adults, the corticospinal tracts are predominantly involved rather than the corpus callosum, possibly due to early ART. Continuous early ART can limit white matter damage

An Exercise Intervention to Unravel the Mechanisms Underlying Insulin Resistance in a Cohort of Black South African Women : Protocol for a Randomized Controlled Trial and Baseline Characteristics of Participants

Background: The pathogenesis of type 2 diabetes (T2D) in black African women is complex and differs from that in their white counterparts. However, earlier studies have been cross-sectional and provide little insight into the causal pathways. Exercise training is consistently used as a model to examine the mechanisms underlying insulin resistance and risk for T2D. Objective: The objective of the study was to examine the mechanisms underlying the changes in insulin sensitivity and secretion in response to a 12-week exercise intervention in obese black South African (SA) women. Methods: A total of 45 obese (body mass index, BMI: 30-40 kg/m2) black SA women were randomized into a control (n=22) or experimental (exercise; n=23) group. The exercise group completed 12 weeks of supervised combined aerobic and resistance training (40-60 min, 4 days/week), while the control group maintained their typical physical activity patterns, and both groups were requested not to change their dietary patterns. Before and following the 12-week intervention period, insulin sensitivity and secretion (frequently sampled intravenous glucose tolerance test) and its primary and secondary determinants were measured. Dietary intake, sleep quality and quantity, physical activity, and sedentary behaviors were measured every 4 weeks. Results: The final sample included 20 exercise and 15 control participants. Baseline sociodemographics, cardiorespiratory fitness, anthropometry, cardiometabolic risk factors, physical activity, and diet did not differ between the groups (P>.05). Conclusions: The study describes a research protocol for an exercise intervention to understand the mechanisms underlying insulin sensitivity and secretion in obese black SA women and aims to identify causal pathways underlying the high prevalence of insulin resistance and risk for T2D in black SA women, targeting specific areas for therapeutic intervention