Influence of vitamin D supplementation on growth, body composition, pubertal development and spirometry in South African schoolchildren: a randomised controlled trial (ViDiKids).

OBJECTIVE: To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. DESIGN: Phase 3 double-blind randomised placebo-controlled trial. SETTING: Socioeconomically disadvantaged peri-urban district of Cape Town, South Africa. PARTICIPANTS: 1682 children of black African ancestry attending government primary schools and aged 6-11 years at baseline. INTERVENTIONS: Oral vitamin D3 (10 000 IU/week) versus placebo for 3 years. MAIN OUTCOME MEASURES: Height-for-age and body mass index-for-age, measured in all participants; Tanner scores for pubertal development, spirometric lung volumes and body composition, measured in a subset of 450 children who additionally took part in a nested substudy. RESULTS: Mean serum 25-hydroxyvitamin D3 concentration at 3-year follow-up was higher among children randomised to receive vitamin D versus placebo (104.3 vs 64.7 nmol/L, respectively; mean difference (MD) 39.7 nmol/L, 95% CI 37.6 to 41.9 nmol/L). No statistically significant differences in height-for-age z-score (adjusted MD (aMD) -0.08, 95% CI -0.19 to 0.03) or body mass index-for-age z-score (aMD -0.04, 95% CI -0.16 to 0.07) were seen between vitamin D versus placebo groups at follow-up. Among substudy participants, allocation to vitamin D versus placebo did not influence pubertal development scores, % predicted forced expiratory volume in 1 s (FEV1), % predicted forced vital capacity (FVC), % predicted FEV1/FVC, fat mass or fat-free mass. CONCLUSIONS: Weekly oral administration of 10 000 IU vitamin D3 boosted vitamin D status but did not influence growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02880982, South African National Clinical Trials Register DOH-27-0916-5527.

Influence of vitamin D supplementation on bone mineral content, bone turnover markers, and fracture risk in South African schoolchildren: multicenter double-blind randomized placebo-controlled trial (ViDiKids).

Randomized controlled trials (RCTs) to determine the influence of vitamin D on BMC and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n = 450) nested within a phase 3 RCT of weekly oral supplementation with 10 000 IU vitamin D3 vs placebo for 3 yr in HIV-uninfected Cape Town schoolchildren aged 6-11 yr. Outcomes were BMC at the whole body less head (WBLH) and LS and serum 25-hydroxyvitamin D3 (25(OH)D3), PTH, alkaline phosphatase, C-terminal telopeptide, and PINP. Incidence of fractures was a secondary outcome of the main trial (n = 1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (SD 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI, 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI, -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI, -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI, -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomized to vitamin D vs placebo (7/755 vs 10/758 attending at least 1 follow-up; adjusted odds ratio 0.70, 95% CI, 0.27 to 1.85). In conclusion, a 3-yr course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.

Vitamin D­the "sunshine vitamin"­is essential for helping the body to absorb calcium from the diet, which is laid down in bone to improve its strength. There is a lack of clinical trials testing whether vitamin D supplements can improve bone content of calcium and other minerals, or reduce risk of bone fractures (broken bones) in children of Black African ancestry. We therefore conducted such a study, recruiting 1682 schoolchildren aged 6­11 yr living in Cape Town, South Africa. We found that a weekly dose of 10 000 international units (250 micrograms) of vitamin D3, given by mouth for 3 yr, was effective in boosting vitamin D levels in trial participants who received it. However, this did not have any effect on bone content of calcium and other minerals. Relatively few children experienced a broken bone during the study, so we were unable to say with confidence whether or not vitamin D supplements might affect this outcome.

Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicenter phase 3 double-blind randomized placebo-controlled trial (ViDiKids).

OBJECTIVES: To determine whether weekly oral supplementation with 10,000 IU vitamin D3 for 3 years reduces the risk of sensitization to M. tuberculosis in South African schoolchildren aged 6-11 years with negative QuantiFERON-tuberculosis (TB) Gold Plus (QFT-Plus) assay results at baseline. METHODS: We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town. The primary outcome was a positive end-trial QFT-Plus result, analyzed using a mixed effects logistic regression model with the school of attendance included as a random effect. RESULTS: 829 vs. 853 QFT-Plus-negative children were randomized to receive vitamin D3 vs. placebo, respectively. Mean end-study 25(OH)D concentrations in participants randomized to vitamin D vs. placebo were 104.3 vs 64.7 nmol/l, respectively (95% confidence interval for difference, 37.6 to 41.9 nmol/l). A total of 76/667 (11.4%) participants allocated to vitamin D vs. 89/687 (13.0%) participants allocated to placebo tested QFT-Plus positive at 3-year follow-up (adjusted odds ratio 0.86, 95% confidence interval 0.62-1.19, P = 0.35). CONCLUSION: Weekly oral supplementation with 10,000 IU vitamin D3 for 3 years elevated serum 25(OH)D concentrations among QFT-Plus-negative Cape Town schoolchildren but did not reduce their risk of QFT-Plus conversion.

Reaching underserved South Africans with integrated chronic disease screening and mobile HIV counselling and testing: A retrospective, longitudinal study conducted in Cape Town.

BACKGROUND: Community-based, mobile HIV counselling and testing (HCT) and screening for non-communicable diseases (NCDs) may improve early diagnosis and referral for care in underserved populations. We evaluated HCT/NCD data and described population characteristics of those visiting a mobile clinic in high HIV disease burden settings in Cape Town, South Africa, between 2008 and 2016. METHODS: Trained counsellors registered patients ≥12 years old at a mobile clinic, which offered HCT and blood pressure, diabetes (glucose testing) and obesity (body mass index) screening. A nurse referred patients who required HIV treatment or NCD care. Using multivariable logistic regression, we estimated correlates of new HIV diagnoses adjusting for gender, age and year. RESULTS: Overall, 43,938 individuals (50% male; 29% <25 years; median age = 31 years) tested for HIV at the mobile clinic, where 27% of patients (66% of males, 34% of females) reported being debut HIV testers. Males not previously tested for HIV had higher rates of HIV positivity (11%) than females (7%). Over half (55%, n = 1,343) of those previously diagnosed HIV-positive had not initiated ART. More than one-quarter (26%) of patients screened positive for hypertension (males 28%, females 24%, p<0.001). Females were more likely overweight (25% vs 20%) or obese (43% vs 9%) and presented with more diabetes symptoms than males (8% vs 4%). Females (3%) reported more symptoms of STIs than males (1%). Reporting symptoms of sexually transmitted infections (aOR = 3.45, 95% CI = 2.84, 4.20), diabetes symptoms (aOR = 1.61, 95% 1.35, 1.92), and TB symptoms (aOR = 4.40, 95% CI = 3.85, 5.01) were associated with higher odds of a new HIV diagnosis after adjusting for covariates. CONCLUSION: Findings demonstrate that mobile clinics providing integrated HCT and NCD screening may offer the opportunity of early diagnosis and referral for care for those who delay screening, including men living with HIV not previously tested.

Global PrEP roll-out: recommendations for programmatic success.

Pre-exposure prophylaxis (PrEP) is being adopted and rolled out in diverse regions, communities, and groups. Although it has been shown to be effective, in some settings PrEP roll-out has lagged, in part due to flawed messaging. Lessons can be learned and principles applied from marketing to highlight the potential pitfalls of current roll-out strategies focused on selective and siloed service provision. After exploration of the way PrEP is promoted in awareness messaging (the sell), marketed to select and often stigmatised groups (the brand), and offered as a special or non-integrated service (product placement), we propose that current strategies can ultimately slow roll-out and contribute to stigma surrounding PrEP use. We propose alternatives for programmes and ministries to consider as they develop long-term plans for HIV prevention. We propose that the sell should focus on protection or wellness framing, the branding should convey PrEP as appropriate for anyone in need, and the provision of PrEP should be placed in the context of other relevant and valued health services. As has been shown in some PrEP programmes, it is possible for programmes to adopt modern marketing strategies that are attractive to healthy clients and might promote an inclusive and holistic vision of biomedical prevention.

Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis.

OBJECTIVE: Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons. DESIGN AND METHODS: The Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft-Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy. RESULTS: There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: -2.4 vs. -1.1 ml/min; P=0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8 ml/min; P=0.02), and resolved after stopping pre-exposure prophylaxis (mean change: -0.1 vs. 0.0 ml/min; P=0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy. CONCLUSIONS: In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.

Resistance in pediatric patients experiencing virologic failure with first-line and second-line antiretroviral therapy.

We examined HIV-1 resistance in children failing first-line and second-line antiretroviral therapy in South Africa, all with clade C virus. Those exposed to full-dose ritonavir had multiple protease resistance mutations. Nineteen percent had wild-type virus. Appropriate antiretroviral therapy sequencing in sub-Saharan African children is essential for prolong treatment options.

Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay: a prospective study.

BACKGROUND: The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown. METHODS AND FINDINGS: Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms. They were clinically characterised and invited to provide two sputum samples at a single visit. The accuracy of the Xpert MTB/RIF assay for diagnosing TB and drug resistance was assessed in comparison with other tests, including fluorescence smear microscopy and automated liquid culture (gold standard) and drug susceptibility testing. Of 515 patients enrolled, 468 patients (median CD4 cell count, 171 cells/µl; interquartile range, 102-236) produced at least one sputum sample, yielding complete sets of results from 839 samples. Mycobacterium tuberculosis was cultured from 81 patients (TB prevalence, 17.3%). The overall sensitivity of the Xpert MTB/RIF assay for culture-positive TB was 73.3% (specificity, 99.2%) compared to 28.0% (specificity, 100%) using smear microscopy. All smear-positive, culture-positive disease was detected by Xpert MTB/RIF from a single sample (sensitivity, 100%), whereas the sensitivity for smear-negative, culture-positive TB was 43.4% from one sputum sample and 62.3% from two samples. Xpert correctly identified rifampicin resistance in all four cases of multidrug-resistant TB but incorrectly identified resistance in three other patients whose disease was confirmed to be drug sensitive by gene sequencing (specificity, 94.1%; positive predictive value, 57%). CONCLUSIONS: In this population of individuals at high risk of TB, intensive screening using the Xpert MTB/RIF assay increased case detection by 45% compared with smear microscopy, strongly supporting replacement of microscopy for this indication. However, despite the ability of the assay to rapidly detect rifampicin-resistant disease, the specificity for drug-resistant TB was sub-optimal.