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The BED assay overestimates HIV incidence because a proportion, epsilon (epsilon), of chronically infected people test "false-recent." In the ZVITAMBO trial, 2796 postpartum women tested HIV positive at baseline and 5.1% tested "false-recent" by BED 12 months later, providing a population-based estimate of epsilon. At baseline, 7.2% (95% CI: 5.3-9.4) of positive women >30 years and 5.1% (95% CI: 3.5-7.2) of positive women with CD4 <200 cells/microl tested "recent" by BED. Thus, the proportions of BED-positive women in either of these subgroups (data that would be available in surveys measuring HIV and BED status) provided a reasonably tight upper bound fo epsilon, which can be used to provide a lower bound for HIV incidence.

A number of risk factors for HIV transmission during breastfeeding have been identified. The experience counseling HIV-infected women on infant feeding options has expanded to consider these risk factors. Programmatic evidence is limited, but the review presented here strongly argues for an end to the polarized debate about whether HIV-infected women should breast or formula feed. In reality, neither alternative is risk-free for HIV-exposed infants, and the balance of risks varies in different settings and over time.

Background Globally, nearly 250 million children (43% of all children under 5 years of age) are at risk of compromised neurodevelopment due to poverty, stunting, and lack of stimulation. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH) and improved infant and young child feeding (IYCF) on early child development (ECD) among children enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. Methods and findings SHINE was a cluster-randomized community-based 2x2 factorial trial. A total of 5,280 pregnant women were enrolled from 211 clusters (defined as the catchment area of 1-4 village health workers [VHWs] employed by the Zimbabwean Ministry of Health and Child Care). Clusters were randomly allocated to standard of care, IYCF (20 g of small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counseling), WASH (ventilated improved pit latrine, handwashing stations, chlorine, liquid soap, and play yard), and WASH + IYCF. Primary outcomes were child length-for-age Z-score and hemoglobin concentration at 18 months of age. Children who completed the 18-month visit and turned 2 years (102-112 weeks) between March 1, 2016, and April 30, 2017, were eligible for the ECD substudy. We prespecified that primary inferences would be drawn from findings of children born to HIV-negative mothers; these results are presented in this paper. A total of 1,655 HIV-unexposed children (64% of those eligible) were recruited into the ECD substudy from 206 clusters and evaluated for ECD at 2 years of age using the Malawi Developmental Assessment Tool (MDAT) to assess gross motor, fine motor, language, and social skills; the MacArthur-Bates Communicative Development Inventories (CDI) to assess vocabulary and grammar; the A-not-B test to assess object permanence; and a self-control task. Outcomes were analyzed in the intention-to-treat population. For all ECD outcomes, there was not a statistical interaction between the IYCF and WASH interventions, so we estimated the effects of the interventions by comparing the 2 IYCF groups with the 2 non-IYCF groups and the 2 WASH groups with the 2 non-WASH groups. The mean (95% CI) total MDAT score was modestly higher in the IYCF groups compared to the non-IYCF groups in unadjusted analysis: 1.35 (0.24, 2.46; p = 0.017); this difference did not persist in adjusted analysis: 0.79 (-0.22, 1.68; p = 0.057). There was no evidence of impact of the IYCF intervention on the CDI, A-not-B, or self-control tests. Among children in the WASH groups compared to those in the non-WASH groups, mean scores were not different for the MDAT, A-not-B, or self-control tests; mean CDI score was not different in unadjusted analysis (0.99 [95% CI -1.18, 3.17]) but was higher in children in the WASH groups in adjusted analysis (1.81 [0.01, 3.61]). The main limitation of the study was the specific time window for substudy recruitment, meaning not all children from the main trial were enrolled. Conclusions We found little evidence that the IYCF and WASH interventions implemented in SHINE caused clinically important improvements in child development at 2 years of age. Interventions that directly target neurodevelopment (e.g., early stimulation) or that more comprehensively address the multifactorial nature of neurodevelopment may be required to support healthy development of vulnerable children. Trial registration ClinicalTrials.gov NCT01824940, Author(s): Melissa J. Gladstone 1,*, Jaya Chandna 1,2, Gwendoline Kandawasvika 3, Robert Ntozini 2, Florence D. Majo 2, Naume V. Tavengwa 2, Mduduzi N. N. Mbuya 2,4, Goldberg T. Mangwadu [...]

Background Clinical outcomes of children who are human immunodeficiency virus (HIV)–exposed in sub-Saharan Africa remain uncertain. Methods The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial evaluated improved infant and young child feeding (IYCF) and/or improved water, sanitation, and hygiene in 2 rural Zimbabwean districts with 15% antenatal HIV prevalence and > 80% prevention of mother-to-child transmission (PMTCT) coverage. Children born between February 2013 and December 2015 had longitudinal HIV testing and anthropometry. We compared mortality and growth between children who were HIV-exposed and HIV-unexposed through 18 months. Children receiving IYCF were excluded from growth analyses. Results Fifty-one of 738 (7%) children who were HIV-exposed and 198 of 3989 (5%) children who were HIV-unexposed (CHU) died (hazard ratio, 1.41 [95% confidence interval {CI}, 1.02–1.93]). Twenty-five (3%) children who were HIV-exposed tested HIV positive, 596 (81%) were HIV-exposed uninfected (CHEU), and 117 (16%) had unknown HIV status by 18 months; overall transmission estimates were 4.3%–7.7%. Mean length-for-age z score at 18 months was 0.38 (95% CI,.24–.51) standard deviations lower among CHEU compared to CHU. Among 367 children exposed to HIV in non-IYCF arms, 147 (40%) were alive, HIV-free, and nonstunted at 18 months, compared to 1169 of 1956 (60%) CHU (absolute difference, 20% [95% CI, 15%–26%]). Conclusions In rural Zimbabwe, mortality remains 40% higher among children exposed to HIV, vertical transmission exceeds elimination targets, and half of CHEU are stunted. We propose the composite outcome of "alive, HIV free, and thriving" as the long-term goal of PMTCT programs. Clinical Trials Registration NCT01824940. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) acquisition and inflammation were evaluated in 231 human immunodeficiency virus (HIV)-exposed uninfected (HEU) and 100 HIV-unexposed Zimbabwean infants aged 6 weeks. The HEU and HIV-unexposed infants had a similarly high prevalence of CMV (81.4% vs 74.0%, respectively; P = .14), but HEU infants had higher CMV loads (P = .005) and >2-fold higher C-reactive protein (CRP) concentrations (P < .0001). The CMV-positive HEU infants had higher CRP than the CMV-negative HEU infants; this association disappeared after adjusting for maternal HIV load. Overall, CMV acquisition is high in early life, but HEU infants have higher CMV loads and a proinflammatory milieu, which may be driven partly by maternal HIV viremia. [ABSTRACT FROM AUTHOR]

Background: In sub-Saharan Africa, one-third of all births are small for gestational age (SGA), and 4.4 million children are stunted; both conditions increase the risk of child mortality. SGA has also been shown to increase the risk of stunting.Objective: We tested whether the association between SGA and postneonatal mortality is mediated by stunting.Methods: We used longitudinal data from children aged 6 wk to 24 mo (n = 12,155) enrolled in the ZVITAMBO (Zimbabwe Vitamin A for Mothers and Babies) trial. HIV exposure was defined based on maternal HIV status at baseline. SGA was defined as birthweight <10th percentile of the INTERGROWTH-21st (International Fetal and Newborn Growth Consortium for the 21st Century) standards. We used a standard mediation approach by comparing the attenuation of the risk when the mediator was added to the model. We used Cox proportional hazards models first to regress SGA on postneonatal mortality, controlling for age. Stunting (length-for-age z score <-2) was then included in the model to test mediation.Results: Approximately 20% of children were term SGA, and 23% were stunted before their last follow-up visit. In this cohort, 31% of children were exposed to HIV; the HIV-exposed group represented a pooled group of HIV-infected and HIV-exposed but uninfected children. Postneonatal mortality was significantly higher among children born SGA (HR: 1.5; 95% CI: 1.3, 1.7). This association was attenuated and not statistically significant when stunting was included in the model, suggesting a mediation effect (HR: 1.1; 95% CI: 0.91, 1.3). When stratified by HIV exposure status, we observed a significant attenuation of the risk, suggesting mediation, only among HIV-exposed children (model 1, HR: 1.3; 95% CI: 1.1, 1.6; model 2, HR: 1.1; 95% CI: 0.88, 1.3).Conclusions: This analysis aids in investigating pathways that underlie an observed SGA-mortality relation and may inform survival interventions in undernourished settings. [ABSTRACT FROM AUTHOR]

Laboratory assays that identify recent HIV infections are important for assessing impacts of interventions aimed at reducing HIV incidence. Kinetics of HIV humoral responses can vary with inherent assay properties, and between HIV subtypes, populations, and physiological states. They are important in determining mean duration of recent infection (MDRI) for antibody-based assays for detecting recent HIV infections. We determined MDRIs for multi-subtype peptide representing subtypes B, E and D (BED)-capture enzyme immunoassay, limiting antigen (LAg), and Bio-Rad Avidity Incidence (BRAI) assays for 101 seroconverting postpartum women, recruited in Harare from 1997 to 2000 during the Zimbabwe Vitamin A for Mothers and Babies trial, comparing them against published MDRIs estimated from seroconverting cases in the general population. We also compared MDRIs for women who seroconverted either during the first 9 months, or at later stages, postpartum. At cutoffs ( C) of 0.8 for BED, 1.5 for LAg, and 40% for BRAI, estimated MDRIs for postpartum mothers were 192, 104, and 144 days, 33%, 32%, and 52% lower than published estimates of 287, 152 and 298 days, respectively, for clade C samples from general populations. Point estimates of MDRI values were 7%-19% shorter for women who seroconverted in the first 9 months postpartum than for those seroconverting later. MDRI values for three HIV incidence biomarkers are longer in the general population than among postpartum women, particularly those who recently gave birth, consistent with heightened immunological activation soon after birth. Our results provide a caution that MDRI may vary significantly between subjects in different physiological states. [ABSTRACT FROM AUTHOR]

Objective: The BED assay was developed to estimate the proportion of recent HIV infections in a population. We used the BED assay as a proxy for acute infection to quantify the associated risk of mother-to-child-transmission (MTCT) during pregnancy and delivery. Design A total of 3773 HIV-1 sero-positive women were tested within 96 h of delivery using the BED assay, and CD4 cell count measurements were taken. Mothers were classified according to their likelihood of having recently seroconverted.Methods: The risk of MTCT in utero and intra-partum was assessed comparing different groups defined by BED and CD4 cell count, adjusting for background factors using multinomial logistic models.Results: Compared with women with BED ≥ 0.8/CD4 ≥ 350 (typical of HIV-1 chronic patients) there was insufficient evidence to conclude that women presenting with BED < 0.8/CD4 ≥ 350 (typical of recent infections) were more likely to transmit in utero [adjusted odds ratio (aOR) = 1.37, 96% confidence interval (CI) 0.90-2.08, P = 0.14], whereas women with BED < 0.8/CD4 200-349 (possibly recently infected patients) had a 2.57 (95% CI 1.39-4.77, P-value < 0.01) odds of transmitting in utero. Women who had BED < 0.8/CD4 < 200 were most likely to transmit in utero (aOR 3.73, 95% CI 1.27-10.96, P = 0.02). BED and CD4 cell count were not predictive of intra-partum infections.Conclusions: These data provide evidence that in utero transmission of HIV might be higher among women who seroconvert during pregnancy. [ABSTRACT FROM AUTHOR]

Little is known about mothers' perspectives and experiences of early breast-feeding cessation as a strategy to reduce postnatal HIV transmission in rural, resource-constrained settings. We conducted in-depth interviews (IDI) with 15 HIV-positive breast-feeding mothers of infants aged 3-5 mo about their plans for feeding their infants after age 6 mo. We also conducted IDI with 12 HIV-positive mothers who intended to stop breast-feeding after receiving their infant's HIV-PCR negative test result at age 6 mo. Twenty-four-hour dietary recalls were conducted with the same 12 mothers and 16 HIV-negative or status unknown mothers who were breast-feeding their 6- to 9-mo-old infants. Of the 12 mothers who intended to stop breast-feeding, 11 did so by 9 mo. Median energy intake (percent requirement) was 1382 kJ (54%) among weaned infants compared with 2234 kJ (87%) among breast-feeding infants. Median intakes were <67% of the recommended levels for 9 and 7 of the 12 micronutrients assessed for weaned and breast-feeding infants, respectively. Factors facilitating early breast-feeding cessation were mothers' knowledge about HIV transmission, family support, and disclosure of their HIV status; food unavailability was the primary barrier. HIV-positive mothers in resource-constrained settings may be so motivated to protect their child from HIV that they stop breast-feeding early even when they cannot provide an adequate replacement diet. As reflected in the new World Health Organization guidance, HIV-positive mothers should continue breastfeeding their infants beyond 6 mo if replacement feeding is still not acceptable, feasible, affordable, sustainable, and safe. [ABSTRACT FROM AUTHOR]

Background: Anemia is prevalent in infants in developing countries. Its etiology is multifactorial and includes vitamin A deficiency. Objective: Our primary aim was to measure the effect of maternal or neonatal vitamin A supplementation (or both) on hemoglobin and anemia in Zimbabwean infants. Our secondary aim was to identify the underlying causes of postnatal anemia. Design: A randomized, placebo-controlled trial was conducted in 14 110 mothers and their infants; 2854 infants were randomly selected for the anemia substudy, of whom 1592 were successfully observed for 8-14 mo and formed the study sample. Infants were randomly assigned within 96 h of delivery to 1 of 4 treatment groups: mothers and infants received vitamin A; mothers received vitamin A and infants received placebo; mothers received placebo and infants received vitamin A; and mothers and infants received placebo. The vitamin A doses were 400 000 and 50 000 IU in the mothers and infants, respectively. Results: Vitamin A supplementation had no effect on hemoglobin or anemia (hemoglobin <105 g/L) in unadjusted or adjusted analyses. Infant HIV infection independently increased anemia risk >6-fold. Additional predictors of anemia in HIV-negative and -positive infants were male sex and lower total body iron at birth. In addition, in HIV-positive infants, the risk of anemia increased with early infection, low maternal CD4+ lymphocyte count at recruitment, and frequent morbidity. Six-month plasma ferritin concentrations <12 μg/L were a risk factor in HIV-negative but not in HIV-positive infants. Maternal HIV infection alone did not cause anemia. Conclusion: Prevention of infantile anemia should include efforts to increase the birth endowment of iron and prevent HIV infection. [ABSTRACT FROM AUTHOR]

Background. Low maternal serum retinol level is a risk factor for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality. The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency, neonatal dosing is under consideration. We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT, HIV-free survival, and mortality in HIV-exposed infants. Methods. A total of 14,110 mother-infant pairs were enrolled ⩽96 h after delivery, and both mother and infant, mother only, infant only, or neither received vitamin A supplementation in a randomized, placebo-controlled trial with a 2 × 2 factorial design. All but 4 mothers initiated breast-feeding. A total of 4495 infants born to HIV-positive women were included in the present analysis. Results. Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall mortality between baseline and 24 months. However, the timing of infant HIV infection modified the effect that supplementation had on mortality. Vitamin A supplementation had no effect in infants who were polymerase chain reaction (PCR) negative for HIV at baseline. In infants who were PCR negative at baseline and PCR positive at 6 weeks, neonatal supplementation reduced mortality by 28% (P = .01), but maternal supplementation had no effect. In infants who were PCR negative at 6 weeks, all 3 vitamin A regimens were associated with ∼2-fold higher mortality (P ⩽ .05). Conclusions. Targeted vitamin A supplementation of HIV-positive children prolongs their survival. However, postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed children who are PCR negative at 6 weeks. These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA)-E and HLA-G molecules act as powerful modulators of the innate immune response. The present study shows that the HLA-EG genetic variant (the HLA-E* 0103 allele) alone is significantly (P = .001) associated with a 4.0-fold decreased risk of human immunodeficiency virus 1 (HIV-1) infection in Zimbabwean women. Furthermore, women carrying the combination of the protective HLA-EG homozygote and HLA-G*0105N heterozygote genotypes had a 12.5-fold decreased risk of HIV-1 infection (P = .03), compared with women carrying neither genotype. These associations remained significant after adjustment was made for other significant sociodemographic risk factors for HIV prevalence in this population. In conclusion, HLA-E and HLA-G polymorphisms can independently and synergistically influence susceptibility to heterosexual acquisition of HIV-1. [ABSTRACT FROM AUTHOR]

International guidance on HIV and infant feeding has evolved over the last decade. In response to these changes, we designed, implemented, and evaluated an education and counseling program for new mothers in Harare, Zimbabwe. The program was implemented within the ZVITAMBO trial, in which 14,110 mother-baby pairs were enrolled within 96 h of delivery and were followed at 6 wk, 3 mo, and 3-mo intervals. Mothers were tested for HIV at delivery but were not required to learn their test results. Infant feeding patterns were determined using data provided up to 3 mo. Formative research was undertaken to guide the design of the program that included group education, individual counseling, videos, and brochures. The program was introduced over a 2-mo period: 11,362, 1311, and 1437 women were enrolled into the trial before, during, and after this period. Exclusive breast-feeding was recommended for mothers of unknown or negative HIV status, and for HIV-positive mothers who chose to breast-feed. A questionnaire assessing HIV knowledge and exposure to the program was administered to 1996 mothers enrolling after the program was initiated. HIV knowledge improved with increasing exposure to the program. Mothers who enrolled when the program was being fully implemented were 70% more likely to learn their HIV status early (<3 mo) and 8.4 times more likely to exclusively breast-feed than mothers who enrolled before the program began. Formative research aided in the design of a culturally sensitive intervention, The intervention increased relevant knowledge and improved feeding practices among women who primarily did not know their HIV status. [ABSTRACT FROM AUTHOR]

The article focuses on the morbidity and mortality among the postpartum HIV-positive and HIV-negative women in Zimbabwe in relation to vitamin A supplementation. It mentions that the single-dose postpartum supplementation of vitamin A had no effect on the maternal mortality. Moreover, vitamin A status was sufficient in the HIV-negative women while unresponsive to supplementation in the HIV-positive women.