Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Contribution of Maternal Antiretroviral Therapy and Breastfeeding to 24-Month Survival in Human Immunodeficiency Virus-Exposed Uninfected Children: An Individual Pooled Analysis of African and Asian Studies

Background: Increasing numbers of HIV-infected pregnant women receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggested that HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but evidence mostly relates to the pre-ART era, breastfeeding of limited duration and considerable maternal mortality. Maternal ART and prolonged breastfeeding under cover of ART may improve survival, although this has not been reliably quantified. Methods: Individual data on 19,219 HEU children from 21 PMTCT trials/cohorts undertaken 1995-2015 in Africa and Asia were pooled and the association between 24-month mortality and maternal/infant factors quantified using random-effects Cox proportional hazards models accounting for between-study heterogeneity. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" estimate the relative contribution of risk factors to overall mortality in HEU children. Results: Cumulative incidence of death was 5.5% (95%CI: 5.1-5.9) by age 24 months. Low birth weight (LBW<2500g, adjusted Hazard Ratio (aHR: 2.9), no breastfeeding (aHR: 2.5) and maternal death (aHR: 11.1) were significantly associated with increased mortality. Maternal ART (aHR: 0.5) was significantly associated with lower mortality. At population level, LBW accounted for 16.2% of child deaths by 24 months, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; these factors combined explained 63.6% of deaths by age 24 months. Conclusion: Survival of HEU children could be substantially improved if public health strategies provided all mothers living with HIV with ART and supported optimal infant feeding and care for LBW neonates

Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy and risk of malaria in early childhood: A randomized controlled trial

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with dihydroartemisinin-piperaquine (IPTp-DP) has been shown to reduce the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (IPTp-SP). However, limited data exist on how IPTp regimens impact malaria risk during infancy. We conducted a double-blinded randomized controlled trial (RCT) to test the hypothesis that children born to mothers given IPTp-DP would have a lower incidence of malaria during infancy compared to children born to mothers who received IPTp-SP. METHODS AND FINDINGS: We compared malaria metrics among children in Tororo, Uganda, born to women randomized to IPTp-SP given every 8 weeks (SP8w, n = 100), IPTp-DP every 8 weeks (DP8w, n = 44), or IPTp-DP every 4 weeks (DP4w, n = 47). After birth, children were given chemoprevention with DP every 12 weeks from 8 weeks to 2 years of age. The primary outcome was incidence of malaria during the first 2 years of life. Secondary outcomes included time to malaria from birth and time to parasitemia following each dose of DP given during infancy. Results are reported after adjustment for clustering (twin gestation) and potential confounders (maternal age, gravidity, and maternal parasitemia status at enrolment).The study took place between June 2014 and May 2017. Compared to children whose mothers were randomized to IPTp-SP8w (0.24 episodes per person year [PPY]), the incidence of malaria was higher in children born to mothers who received IPTp-DP4w (0.42 episodes PPY, adjusted incidence rate ratio [aIRR] 1.92; 95% CI 1.00-3.65, p = 0.049) and nonsignificantly higher in children born to mothers who received IPT-DP8w (0.30 episodes PPY, aIRR 1.44; 95% CI 0.68-3.05, p = 0.34). However, these associations were modified by infant sex. Female children whose mothers were randomized to IPTp-DP4w had an apparently 4-fold higher incidence of malaria compared to female children whose mothers were randomized to IPTp-SP8w (0.65 versus 0.20 episodes PPY, aIRR 4.39, 95% CI 1.87-10.3, p = 0.001), but no significant association was observed in male children (0.20 versus 0.28 episodes PPY, aIRR 0.66, 95% CI 0.25-1.75, p = 0.42). Nonsignificant increases in malaria incidence were observed among female, but not male, children born to mothers who received DP8w versus SP8w. In exploratory analyses, levels of malaria-specific antibodies in cord blood were similar between IPTp groups and sex. However, female children whose mothers were randomized to IPTp-DP4w had lower mean piperaquine (PQ) levels during infancy compared to female children whose mothers received IPTp-SP8w (coef 0.81, 95% CI 0.65-1.00, p = 0.048) and male children whose mothers received IPTp-DP4w (coef 0.72, 95% CI 0.57-0.91, p = 0.006). There were no significant sex-specific differences in PQ levels among children whose mothers were randomized to IPTp-SP8w or IPTp-DP8w. The main limitations were small sample size and childhood provision of DP every 12 weeks in infancy. CONCLUSIONS: Contrary to our hypothesis, preventing malaria in pregnancy with IPTp-DP in the context of chemoprevention with DP during infancy does not lead to a reduced incidence of malaria in childhood; in this setting, it may be associated with an increased incidence of malaria in females. Future studies are needed to better understand the biological mechanisms of in utero drug exposure on drug metabolism and how this may affect the dosing of antimalarial drugs for treatment and prevention during infancy. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02163447

“I Have Remained Strong Because of That Food”: Acceptability and Use of Lipid-Based Nutrient Supplements Among Pregnant HIV-Infected Ugandan Women Receiving Combination Antiretroviral Therapy

We evaluated the acceptability and use of macronutrient supplementation among HIV-infected pregnant Ugandan women receiving antiretroviral therapy in a clinical study (NCT 00993031). We first conducted formative research among 56 pregnant and lactating women to select a supplement regimen. Acceptability and use of the supplementation regimen [35 sachets of lipid-based nutrient supplements (LNS) and 4 or 6 kg of instant soy porridge for the household provided monthly] were evaluated among 87 pregnant women. Organoleptic assessments of LNS were favorable. Participants reported consuming LNS a mean of 6.1 days per week, and adherence to recommended consumption behaviors (e.g. frequency, quantity, not sharing) was >80%. Few women reported negative social consequences of supplementation. The majority of participants also consumed most of the porridge intended for the household. In sum, LNS was acceptable and used regularly. Larger studies to evaluate physical and psychosocial consequences of LNS during pregnancy among HIV-infected women are warranted