Micronutrients, Metabolic Complications, and Inflammation in Ugandan Children With HIV.

BACKGROUND: Selenium, zinc, and chromium are essential micronutrients. Their alterations have been associated with HIV disease progression, metabolic complications, and mortality. METHODS: This is a cross-sectional study in children with perinatally acquired HIV (PHIV, n = 57), HIV-exposed uninfected (HEU, n = 59), and HIV-unexposed uninfected (HIV-, n = 56) children aged 2 to 10 years old, age- and sex-matched, enrolled in Uganda. PHIV were on stable antiretroviral therapy (ART) with undetectable viral load. We measured plasma concentrations of selenium, zinc, and chromium as well as markers of systemic inflammation, monocyte activation, and gut integrity. RESULTS: Among PHIV children, 93% had viral load ≤20 copies/mL, median CD4 was 37%, and 77% were receiving a nonnucleotide reserve transcriptase regimen. Median age of all participants was 8 years and 55% were girls. Median selenium concentrations were higher in PHIV compared with the HEU and HIV groups (P < 0.001), 46% of children overall had low zinc status (P = 0.18 between groups). Higher selenium, but not chromium or zinc, was associated with lower IL6, sTNFRI and II, and higher beta d glucan, a marker of fungal translocation, zonulin, a marker of gut permeability, oxidized LDL and insulin resistance (P ≤ 0.01). CONCLUSION: In this cohort of PHIV on ART in Uganda, there is a high prevalence of low zinc status overall. Higher plasma selenium concentrations were associated with lower systemic inflammation and higher gut integrity markers. Although our findings do not support the use of micronutrient supplementation broadly for PHIV in Uganda, further studies are warranted to assess the role of selenium supplements in attenuating heightened inflammation.

Brief Report: Zinc Supplementation and Inflammation in Treated HIV.

OBJECTIVE: In this study, we explored the effect of zinc supplementation on markers of inflammation and monocyte activation in antiretroviral therapy-treated HIV infection. METHODS: This is a phase I open-labeled randomized double-arm study, exploring the efficacy and safety of zinc supplementation on inflammation in ≥18-year-old people living with HIV in the US, on stable antiretroviral therapy and with zinc levels ≤75 µg/dL in the last 60 days. Patients were randomized 1:1 to zinc gluconate capsules at a dose of 45 mg (low-dose), or 90 mg (high-dose) elemental zinc daily for 16 weeks. We assessed inflammatory and gut integrity biomarkers at baseline and 16 weeks. RESULTS: Overall, a total of 52 participants were enrolled (25 participants in the low-dose arm and 27 participants in the high-dose arm). Median (Interquartile range) age was 49 (38, 60) years, 77% were men and 73% were African Americans. At baseline, median zinc levels were 73 (64, 86) µg/dL. Median circulating zinc levels increased to 91 µg/dL in the low-dose arm and to 100 µg/dL in the high-dose arm. Overall, 48%-60% of participants experienced a reduction in biomarkers levels. The margin of reduction ranged between 8% and 21%. This change was meaningful with large effect size (Cohen D ranging from 5 to 19). CONCLUSIONS: In this pilot study, we found that zinc supplementation is effective at increasing circulating zinc levels. In addition, our findings provide novel data suggesting that zinc can affect a biological signature in people living with HIV and modulate biomarkers associated with clinical comorbidities.

Baseline Vitamin D Deficiency Decreases the Effectiveness of Statins in HIV-Infected Adults on Antiretroviral Therapy.

OBJECTIVE: Vitamin D deficiency is common in HIV. Statins may increase vitamin D, and it is unknown whether vitamin D modifies the effect of statins on cardiovascular disease. DESIGN: SATURN-HIV was a 96-week, randomized, placebo-controlled trial designed to evaluate the effect of rosuvastatin on immune activation and subclinical vascular disease in HIV-infected adults on antiretroviral therapy. This analysis focuses on the prespecified secondary endpoint 25-hydroxyvitamin D [25(OH)D] concentrations. METHODS: Mixed effects linear modeling and analysis of variance were used to assess the rosuvastatin effect on plasma 25(OH)D concentrations over time and to determine whether baseline vitamin D modifies the rosuvastatin effect on changes in outcomes over the trial. RESULTS: Hundred forty-seven adults were randomized (72 to rosuvastatin and 75 to placebo); 78% were men, 68% African American, with a mean age of 45 years. Baseline 25(OH)D concentrations were similar (overall mean 18 ng/mL) with 65% of participants below 20 ng/mL. Changes in 25(OH)D at 96 weeks were small and not significant within- or between-rosuvastatin and placebo groups. There were significant group by vitamin D status interactions for changes in low-density lipoprotein-cholesterol, proportion of patrolling monocytes expressing tissue factor (CD14dimCD16+TF+), lipoprotein-associated phospholipase A2, and common carotid artery intima media thickness at most time points. For each of these outcomes, the beneficial effects of rosuvastatin were either not apparent or attenuated in participants with 25(OH)D <20 ng/mL. CONCLUSIONS: Although 25(OH)D did not change with rosuvastatin, baseline vitamin D deficiency decreased the effectiveness of rosuvastatin. Vitamin D supplementation may be warranted for deficient patients initiating statin therapy.

The effect of physical activity on cardiometabolic health and inflammation in treated HIV infection.

BACKGROUND: In HIV-uninfected populations, physical activity decreases mortality and inflammation. Inflammation is a potential cause of comorbidities in HIV+ adults, the evidence examining the effect of physical activity on cardiometabolic health is limited. This analysis examines the relationship between physical activity, cardiometabolic health and inflammation. METHODS: We conducted a nested study within the SATURN-HIV trial in which 147 HIV+ adults were randomized to 10 mg daily rosuvastatin or placebo. Measures of physical activity, cardiometabolic health, inflammation and vascular disease (carotid artery intima media thickness and computed tomography-acquired measures pericardial fat volume) were assessed at baseline and through 96 weeks. Spearman correlations and multivariable analyses were used to explore relationships between physical activity, cardiometabolic health and inflammation. RESULTS: Median age (Q1, Q3) was 46 (40.4, 52.7) years, 80% were male, 69% were African American and 46% were on protease inhibitors. Baseline median physical activity was 44 min per week (0, 150), 24% of participants performed greater than 150 min per week. At baseline, physical activity correlated with several markers of cardiometabolic health and inflammation (all P≤0.05). Over all time points median physical activity was independently associated with carotid distensibility (ß=2.53; P=0.008), pericardial fat volume (ß=-6.13; P=0.001) and interleukin-6 (ß=-0.468; P<0.001). CONCLUSIONS: Physical activity is associated with vascular disease, endothelial function, and may be an adjuvant to decreasing comorbidities in HIV+ adults. Further studies should examine long-term effects of physical activity on cardiometabolic health and inflammation in this population. Clinicaltrials.gov NCT01218802.

The increasing impact of food production on nutrient export by rivers to the Bay of Bengal 1970-2050.

The objective of this study is to assess the impact of food production on river export of nutrients to the coastal waters of the Bay of Bengal in the past (1970 and 2000) and the future (2030 and 2050), and the associated potential for coastal eutrophication. We model nutrient export from land to sea, using the Global NEWS (Nutrient Export from WaterSheds) approach. We calculate increases in river export of N and P over time. Agricultural sources account for about 70-80% of the N and P in rivers. The coastal eutrophication potential is high in the Bay. In 2000, nutrient discharge from about 85% of the basin area of the Bay drains into coastal seas contributes to the risk of coastal eutrophication. By 2050, this may be 96%. We also present an alternative scenario in which N and P inputs to the Bay are 20-35% lower than in the baseline.