Formula-Feeding of HIV-Exposed Uninfected African Children Is Associated with Faster Growth in Length during the First 6 Months of Life in the Kesho Bora Study.

Background: Early feeding patterns may affect the growth of HIV-exposed children and thus their subsequent health and cognition.Objective: We assessed the association of infant feeding (IF) mode with length-for-age z score (LAZ) and stunting from age 2 d to 18 mo in HIV-exposed African children within a controlled randomized trial, which evaluated triple antiretrovirals initiated during pregnancy and continued for 6 mo postpartum to prevent HIV transmission.Methods: HIV-infected pregnant women with CD4+ counts of 200-500 cells/mm3 from Burkina Faso, Kenya, and South Africa were advised to exclusively breastfeed for up to 6 mo or to formula-feed from birth. Factors associated with LAZ were investigated in all uninfected children by using mixed-effects linear models; those associated with stunting (LAZ <-2) at 6 or 12 mo were assessed in multiple logistic regression after exclusion of children stunted at age 2 d. Independent variables were IF mode: formula feeding (FF), exclusive breastfeeding (EBF) <3 mo, or EBF ≥3 mo (reference); sex; trial arm; maternal characteristics; and site.Results: Among 728 children, FF was associated with a greater increase in LAZ from 2 d to 6 mo (+0.07 z score/mo, P < 0.001). Between 6 and 18 mo, FF and EBF <3 mo were both associated with greater mean LAZ than was EBF ≥3 mo (+0.52 z scores and +0.43 z scores, respectively, P < 0.001). Among children not stunted at 2 d, FF was independently associated with a reduced risk of stunting at 6 mo (OR: 0.24; 95% CI: 0.07, 0.81; P = 0.021), whereas EBF <3 mo was not (OR: 0.49; 95% CI: 0.22, 1.10; P = 0.09).Conclusions: In this observational study of HIV-exposed uninfected infants, growth in length in the first 6 mo of life was faster in formula-fed infants than in exclusively breastfed infants. The plausibility of residual confounding and reverse causality is discussed. This trial was registered at www.controlled-trials.com as ISRCTN71468401.

Evaluation of a Systems Analysis and Improvement Approach to Optimize Prevention of Mother-To-Child Transmission of HIV Using the Consolidated Framework for Implementation Research.

BACKGROUND: Despite large investments to prevent mother-to-child-transmission (PMTCT), pediatric HIV elimination goals are not on track in many countries. The Systems Analysis and Improvement Approach (SAIA) study was a cluster randomized trial to test whether a package of systems engineering tools could strengthen PMTCT programs. We sought to (1) define core and adaptable components of the SAIA intervention, and (2) explain the heterogeneity in SAIA's success between facilities. METHODS: The Consolidated Framework for Implementation Research (CFIR) guided all data collection efforts. CFIR constructs were assessed in focus group discussions and interviews with study and facility staff in 6 health facilities (1 high-performing and 1 low-performing site per country, identified by study staff) in December 2014 at the end of the intervention period. SAIA staff identified the intervention's core and adaptable components at an end-of-study meeting in August 2015. Two independent analysts used CFIR constructs to code transcripts before reaching consensus. RESULTS: Flow mapping and continuous quality improvement were the core to the SAIA in all settings, whereas the PMTCT cascade analysis tool was the core in high HIV prevalence settings. Five CFIR constructs distinguished strongly between high and low performers: 2 in inner setting (networks and communication, available resources) and 3 in process (external change agents, executing, reflecting and evaluating). DISCUSSION: The CFIR is a valuable tool to categorize elements of an intervention as core versus adaptable, and to understand heterogeneity in study implementation. Future intervention studies should apply evidence-based implementation science frameworks, like the CFIR, to provide salient data to expand implementation to other settings.

Morbidity in relation to feeding mode in African HIV-exposed, uninfected infants during the first 6 mo of life: the Kesho Bora study.

BACKGROUND: Refraining from breastfeeding to prevent HIV transmission has been associated with increased morbidity and mortality in HIV-exposed African infants. OBJECTIVE: The objective was to assess risks of common and serious infectious morbidity by feeding mode in HIV-exposed, uninfected infants ≤6 mo of age with special attention to the issue of reverse causality. DESIGN: HIV-infected pregnant women from 5 sites in Burkina Faso, Kenya, and South Africa were enrolled in the prevention of mother-to-child transmission Kesho Bora trial and counseled to either breastfeed exclusively and cease by 6 mo postpartum or formula feed exclusively. Maternal-reported morbidity (fever, diarrhea, and vomiting) and serious infectious events (SIEs) (gastroenteritis and lower respiratory tract infections) were investigated for 751 infants for 2 age periods (0-2.9 and 3-6 mo) by using generalized linear mixed models with breastfeeding as a time-dependent variable and adjustment for study site, maternal education, economic level, and cotrimoxazole prophylaxis. RESULTS: Reported morbidity was not significantly higher in nonbreastfed compared with breastfed infants [OR: 1.31 (95% CI: 0.97, 1.75) and 1.21 (0.90, 1.62) at 0-2.9 and 3-6 mo of age, respectively]. Between 0 and 2.9 mo of age, never-breastfed infants had increased risks of morbidity compared with those of infants who were exclusively breastfed (OR: 1.49; 95% CI: 1.01, 2.2; P = 0.042). The adjusted excess risk of SIEs in nonbreastfed infants was large between 0 and 2.9 mo (OR: 6.0; 95% CI: 2.2, 16.4; P = 0.001). Between 3 and 6 mo, the OR for SIEs was sensitive to the timing of breastfeeding status, i.e., 4.3 (95% CI: 1.2, 15.3; P = 0.02) when defined at end of monthly intervals and 2.0 (95% CI: 0.8, 5.0; P = 0.13) when defined at the beginning of intervals. Of 52 SIEs, 3 mothers reported changes in feeding mode during the SIE although none of the mothers ceased breastfeeding completely. CONCLUSIONS: Not breastfeeding was associated with increased risk of serious infections especially between 0 and 2.9 mo of age. The randomized controlled trial component of the Kesho Bora study was registered at Current Controlled Trials (www.controlled-trials.com) as ISRCTN71468401.