SummaryBackgroundChild stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe.MethodsWe did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940.FindingsBetween Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08–0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28–2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported.InterpretationHousehold-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not r...

Background Late initiation of HIV antiretroviral therapy (ART) in pregnancy is associated with not achieving viral suppression before giving birth and increased mother-to-child transmission of HIV. We aimed to investigate virological suppression before giving birth with dolutegravir compared with efavirenz, when initiated during the third trimester. MethodsIn this randomised, open-label trial, DolPHIN-2, we recruited pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating ART in third trimester. Participants were randomly assigned (1:1) to dolutegravir-based or efavirenz-based therapy. HIV viral load was measured 7 days and 28 days after antiretroviral initiation, at 36 weeks' gestation, and at the post-partum visit (0-14 days post partum). The primary efficacy outcome was a viral load of less than 50 copies per mL at the first post-partum visit, and the primary safety outcome was the occurrence of drug-related adverse events in mothers and infants until the post-partum visit. Longer-term follow-up of mothers and infants continues. This study is registered with ClinicalTrials.gov, NCT03249181.Findings Between Jan 23, and Aug 15, 2018, we randomly assigned 268 mothers to dolutegravir (135) or efavirenz (133). All mothers and their infants were included in the safety analysis, and 250 mothers (125 in the dolutegravir group, 125 in the efavirenz group) and their infants in efficacy analyses, by intention-to-treat analyses. The median duration of maternal therapy at birth was 55 days (IQR 33-77). 89 (74%) of 120 in the dolutegravir group had viral loads less than 50 copies per mL, compared with 50 (43%) of 117 in the efavirenz group (risk ratio 1•64, 95% CI 1•31-2•06). 30 (22%) of 137 mothers in the dolutegravir group reported serious adverse events compared with 14 (11%) of 131 in the efavirenz group (p=0•013), particularly surrounding pregnancy and puerperium. We found no differences in births less than 37 weeks and less than 34 weeks gestation (16•4% vs 3•3%, across both groups). Three stillbirths in the dolutegravir group and one in the efavirenz group were considered unrelated to treatment. Three infant HIV infections were detected, all in the dolutegravir group, and were considered likely to be in-utero transmissions.Interpretation Our data support the revision to WHO guidelines recommending the transition to dolutegravir in first-line ART for all adults, regardless of pregnancy or child-bearing potential.Funding Unitaid.

Child stunting and anemia are intractable public health problems in developing countries and have profound short- and long-term consequences. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial is motivated by the premise that environmental enteric dysfunction (EED) is a major underlying cause of both stunting and anemia, that chronic inflammation is the central characteristic of EED mediating these adverse effects, and that EED is primarily caused by high fecal ingestion due to living in conditions of poor water, sanitation, and hygiene (WASH). SHINE is a proof-of-concept, 2 × 2 factorial, cluster-randomized, community-based trial in 2 rural districts of Zimbabwe that will test the independent and combined effects of protecting babies from fecal ingestion (factor 1, operationalized through a WASH intervention) and optimizing nutritional adequacy of infant diet (factor 2, operationalized through an infant and young child feeding [IYCF] intervention) on length and hemoglobin at 18 months of age. Within SHINE we will measure 2 causal pathways. The program impact pathway comprises the series of processes and behaviors linking implementation of the interventions with the 2 child health primary outcomes; it will be modeled using measures of fidelity of intervention delivery and household uptake of promoted behaviors and practices. We will also measure a range of household and individual characteristics, social interactions, and maternal capabilities for childcare, which we hypothesize will explain heterogeneity along these pathways. The biomedical pathway comprises the infant biologic responses to the WASH and IYCF interventions that ultimately result in attained stature and hemoglobin concentration at 18 months of age; it will be elucidated by measuring biomarkers of intestinal structure and function (inflammation, regeneration, absorption, and permeability); microbial translocation; systemic inflammation; and hormonal determinants of growth and anemia among a subgroup of infants enrolled in an EED substudy. This article describes the rationale, design, and methods underlying the SHINE trial.Clinical Trials Registration. NCT01824940.

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