Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial.

BACKGROUND: In sub-Saharan Africa, severely immunocompromised HIV-infected individuals have a high risk of mortality during the first few months after starting antiretroviral therapy (ART). We hypothesise that universally providing ready-to-use supplementary food (RUSF) would increase early weight gain, thereby reducing early mortality compared with current guidelines recommending ready-to-use therapeutic food (RUTF) for severely malnourished individuals only. METHODS: We did a 2 × 2 × 2 factorial, open-label, parallel-group trial at inpatient and outpatient facilities in eight urban or periurban regional hospitals in Kenya, Malawi, Uganda, and Zimbabwe. Eligible participants were ART-naive adults and children aged at least 5 years with confirmed HIV infection and a CD4 cell count of fewer than 100 cells per μL, who were initiating ART at the facilities. We randomly assigned participants (1:1) to initiate ART either with (RUSF) or without (no-RUSF) 12 weeks' of peanut-based RUSF containing 1000 kcal per day and micronutrients, given as two 92 g packets per day for adults and one packet (500 kcal per day) for children aged 5-12 years, regardless of nutritional status. In both groups, individuals received supplementation with RUTF only when severely malnourished (ie, body-mass index [BMI] 0·7). Through 48 weeks, adults and adolescents aged 13 years and older in the RUSF group had significantly greater gains in weight, BMI, and MUAC than the no-RUSF group (p=0·004, 0·004, and 0·03, respectively). The most common type of serious adverse event was specific infections, occurring in 90 (10%) of 897 participants assigned RUSF and 87 (10%) of 908 assigned no-RUSF. By week 48, 205 participants had serious adverse events in both groups (p=0·81), and 181 had grade 4 adverse events in the RUSF group compared with 172 in the non-RUSF group (p=0·45). INTERPRETATION: In severely immunocompromised HIV-infected individuals, providing RUSF universally at ART initiation, compared with providing RUTF to severely malnourished individuals only, improved short-term weight gain but not mortality. A change in policy to provide nutritional supplementation to all severely immunocompromised HIV-infected individuals starting ART is therefore not warranted at present. FUNDING: Joint Global Health Trials Scheme (UK Medical Research Council, UK Department for International Development, and Wellcome Trust).This study was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development (DFID), the Wellcome Trust, and the UK Medical Research Council (MRC; G1100693). Additional funding support was provided by the PENTA foundation and core support to the MRC Clinical Trials Unit at University College London (London, UK; MC_UU_12023/23, MC_UU_12023/26). Cipla, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for the study and ready-to-use supplementary food was purchased from Valid International. The MRC Clinical Trials Unit has received other funding from Tibotec and Gilead Sciences for data safety monitoring board membership and lectures. The Malawi–Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (101113/Z/13/Z), and the KEMRI/Wellcome Trust Research Programme, Kilifi (203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust (UK)

Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.

This article has been accepted for publication in Clinical Infectious Diseases Published by Oxford University PressBackground: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts .1). Results: Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/µL), but low symptom burden and maintained fat mass. The remaining groups had 4%-6% mortality. Conclusions: Clinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up. Clinical Trials Registration: ISRCTN43622374.REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation

Improving iron and folic acid supplementation among pregnant women : an implementation science approach in east-central Uganda

Introduction: To address maternal iron-deficiency anemia and low uptake of iron and folic acid supplementation (IFAS) among antenatal care (ANC) clinic attendees in East-Central Uganda, the Anemia Implementation Science Initiative embedded enhanced quality improvement (QI) activities into an integrated health project utilizing QI methodologies. Methods: To address 2 bottlenecks of stock-outs and inadequate health education for pregnant women during ANC, an enhanced QI intervention was implemented from July 2019 to September 2020 in 2 districts. We conducted a mixed-methods effectiveness quasi-experimental study to assess whether the intervention increased the availability of IFAS in the intervention districts. We used longitudinal facility-level data from 2 treatment districts and 1 comparison district for the quantitative results. Difference-in-difference estimation was used to measure the impact of the intervention on IFAS health education and IFA availability at the health facility. We used logistic regression modeling to control for factors associated with IFAS uptake and potential differences in baseline values. Researchers conducted exit interviews with ANC clients and in-depth interviews with providers and district managers for greater insights into the implementation process. Results: The intervention increased the probability, at a statistically significant level, of pregnant women both receiving IFAS and receiving health education on IFAS during ANC. According to interviewees, the intervention approach improved stakeholder engagement and buy-in, which brought about change at all levels of the health system. Discussion: The intervention successfully addressed the 2 main bottlenecks to availability of IFAS for pregnant women attending ANC-inadequate provision of IFAS education and a weak drug quantification process. Even without additional funds to purchase commodities, this approach improved district capacity to advocate for and manage IFAS commodities. It could also be used to strengthen overall ANC quality