Health outcomes of HIV-exposed uninfected African infants

To evaluate severe (grade 3/4) morbidity and mortality in HIV-exposed, uninfected infants

Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

ABSTRACT Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections

Stopping the control arm in response to the DSMB: Mother's choice of HIV prophylaxis during breastfeeding in the BAN Study

The Data and Safety Monitoring Board (DSMB) for the Breastfeeding, Antiretrovirals, and Nutrition study, a clinical trial aimed to prevent postnatal HIV transmission, recommended halting randomization to the enhanced standard-of-care (control) arm. The 67 mother-infant pairs on the control arm and less than 21 weeks postpartum at the time of the DSMB recommendation were read a script informing them of the DSMB decision and offering them the the maternal or infant antiretroviral interventions for the remainder of the 28-week breastfeeding period. This paper describes the BAN study response to the DSMB decision and what the women on the control arm chose, when given a choice to start the maternal or infant antiretroviral interventions

Use of Lipid-Based Nutrient Supplements by HIV-Infected Malawian Women during Lactation Has No Effect on Infant Growth from 0 to 24 Weeks

The Breastfeeding, Antiretrovirals, and Nutrition Study evaluated the effect of daily consumption of lipid-based nutrient supplements (LNS) by 2121 lactating, HIV-infected mothers on the growth of their exclusively breast-fed, HIV-uninfected infants from 0 to 24 wk. The study had a 2 × 3 factorial design. Malawian mothers with CD4+ ≥250 cells/mm3, hemoglobin ≥70 g/L, and BMI ≥17 kg/m2 were randomized within 36 h of delivery to receive either no LNS or 140 g/d of LNS to meet lactation energy and protein needs, and mother-infant pairs were assigned to maternal antiretroviral drugs (ARV), infant ARV, or no ARV. Sex-stratified, longitudinal, random effects models were used to estimate the effect of the 6 study arms on infant weight, length, and BMI. Logistic regression models were used to calculate the odds of growth faltering [decline in weight-for-age Z-score (WAZ) or length-for-age Z-score (LAZ) >0.67] using the control arm as the reference. Although some differences between study arms emerged with increasing infant age in boys, there were no consistent effects of the maternal supplement across the 3 growth outcomes in longitudinal models. At the ages where differences were observed, the effects on weight and BMI were quite small (≤200 g and ≤0.4 kg/m2) and unlikely to be of clinical importance. Overall, 21 and 34% of infants faltered in WAZ and LAZ, respectively. Maternal supplementation did not reduce the odds of infant weight or length faltering from 0 to 24 wk in any arm. These results indicate that blanket supplementation of HIV-infected lactating women may have little impact on infant growth

Maternal Mid–Upper Arm Circumference Is Associated With Birth Weight Among HIV-Infected Malawians

We examined the relationship of maternal anthropometry to fetal growth and birth weight among 1005 HIV-infected women in Lilongwe, Malawi, who consented to enrollment in the Breastfeeding, Antiretrovirals, and Nutrition (BAN) Study (www.thebanstudy.org). Anthropometric assessments of mid-upper arm circumference (MUAC), arm muscle area (AMA), and arm fat area (AFA) were collected at the baseline visit between 12 and 30 weeks gestation and in up to 4 follow-up prenatal visits. In longitudinal analysis, fundal height increased monotonically at an estimated rate of 0.92 cm/week and was positively and negatively associated with AMA and AFA, respectively. These latter relationships varied over weeks of follow-up. Baseline MUAC, AMA, and AFA were positively associated with birth weight [MUAC: 31.84 grams per cm increment, 95% CI: 22.18, 41.49 (p2, 95% CI: 2.51, 11.26 (p2, 95% CI: 3.53, 10.41 (

Reducing lost to follow-up in a large clinical trial of prevention of mother-to-child transmission of HIV: The Breastfeeding, Antiretrovirals and Nutrition study experience

Retaining patients in prevention of mother-to-child transmission of HIV studies can be challenging in resource limited settings, where high lost to follow-up (LTFU) rates have been reported. In this paper, we describe the effectiveness of methods used to encourage retention in the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study and analyze factors associated with LTFU in the study

Effects of Cotrimoxazole Prophylactic Treatment on Adverse Health Outcomes Among HIV-exposed, Uninfected Infants

The World Health Organization guidelines recommend cotrimoxazole prophylactic treatment (CPT) for all HIV-exposed infants from age 6 weeks to the cessation of breastfeeding and the exclusion of HIV infection. There are limited data about the effects of CPT among this population of infants. We examined the effects of CPT on adverse health outcomes among HIV-exposed infants during the first 36 weeks of life by using data from the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study, a large clinical trial of antiretroviral drugs given to the mother or infant for prevention of HIV transmission during breastfeeding

Patterns of Body Composition Among HIV-Infected, Pregnant Malawians and the Effects of Famine Season

We describe change in weight, midupper arm circumference (MUAC), arm muscle area (AMA) and arm fat area (AFA) in 1130 pregnant HIV-infected women with CD4 counts > 200 as part of the BAN Study (www.thebanstudy.org), a randomized, controlled clinical trialto evaluate antiretroviral and nutrition interventions to reducemother-to-child transmission of HIV during breast feeding. In a longitudinal analysis, we found a linear increase in weight with a mean rate of weight gain of 0.27 kgs/wk, from baseline (12 to 30 wks gestation) until the last follow-up visit (32 to 38 wks). Analysis of weight gain showed that 17.1% of the intervals between visits resulted in a weight loss. In unadjusted models, MUAC and AMA increased and AFA declined during late pregnancy. Based on multivariable regression analysis, exposure to the famine season resulted in larger losses in AMA [−0.08, 95%CI: −0.14, −0.02; p=0.01] while AFA losses occurred irrespective of season [−0.55, 95%: −0.95, −0.14, p=0.01]. CD4 was associated with AFA [0.21, 95%CI: 0.01, 0.41, p=.04]. Age was positively associated with MUAC and AMA. Wealth index was positively associated with MUAC, AFA, and weight. While patterns of anthropometric measures among HIV-infected, pregnant women were found to be similar to those reported for uninfected women in sub-Saharan Africa, effects of the famine season among undernourished, Malawian women are of concern. Strategies to optimize nutrition during pregnancy for these women appear warranted

Lipid-Based Nutrient Supplements Are Feasible As a Breastmilk Replacement for HIV-Exposed Infants from 24 to 48 Weeks of Age

The Breastfeeding, Antiretrovirals, and Nutrition (BAN) Study randomized HIV-infected mothers and their infants to receive either maternal lipid-based nutrient supplements (LNS) during lactation or no LNS and then to 1 of 3 antiretroviral drug (ARV) arms (maternal, infant, or no drugs). Assigned interventions were provided from 0 to 28 wk and all infants (n = 1619) were given LNS during (24–28 wk) and following (28–48 wk) weaning. This paper assesses the feasibility of infant LNS as a breastmilk replacement and uses longitudinal random effects models to examine associations of interventions, morbidity, and season with weight-for-age (WAZ), length-for-age (LAZ), and BMI-for-age (BMIZ) Z-scores from 24 to 48 wk. Infant LNS adherence was high (94.1% ate it daily). From 24 to 48 wk, mean WAZ (−0.42 to −0.76 SD; P 0 throughout. A higher LAZ was associated with assignment to the maternal LNS arm (β=0.19; P < 0.05). Lower WAZ and BMIZ were associated with seasonal food insecurity (β=−0.08 and −0.09, respectively; both P < 0.001), fever (β=−0.07 and −0.13; both P < 0.001), diarrhea (β=−0.19 and −0.23; both P < 0.001), and assignment to the infant ARV arm (β=−0.17 and −0.17; both P < 0.05). The magnitude of the season and morbidity effects was small and BAN infants had higher weights and lengths than their counterparts in the general population. High LNS adherence and the modest impact of morbidity on growth indicate that LNS is a feasible breastmilk replacement for HIV-exposed infants weaned early, but controlled trials are needed to quantify the effects of LNS on growth in this population

The Health of HIV-exposed Children after Early Weaning

There are potential health risks associated with the use of early weaning to prevent mother-to-child transmission of HIV in resource-poor settings. Our objective was to examine growth and nutrient inadequacies among a cohort of children weaned early. Children participating in the Breastfeeding Antiretrovirals and Nutrition (BAN) Study in Lilongwe, Malawi, had HIV-infected mothers, were weaned at 6 months and fed LNS until 12 months. 40 HIV-negative, BAN-exited children were compared to 40 HIV-negative, community children matched on age, gender and local health clinic. Nutrient intake was calculated from 24-hour dietary recalls collected from BAN-exited children. Anthropometric measurements were collected from BAN-exited and matched community children at 15-16 months, and 2 months later. Longitudinal random effects sex-stratified models were used to evaluate anthropometric differences between the 2 groups. BAN-exited children consumed adequate energy, protein, and carbohydrates but inadequate amounts of fat. The prevalence of inadequate micronutrient intakes were: 46% for vitamin A; 20% for vitamin B6; 69% for folate; 13% for vitamin C; 19% for iron; 23% for zinc. Regarding growth, BAN-exited girls gained weight at a significantly lower rate (0.02g/kg/day [95%CI: 0.01, 0.03] than their matched comparison (0.05g/kg/day [95%CI: 0.03, 0.07]); BAN girls grew significantly slower (0.73cm/month [95%CI: 0.40,1.06]) than their matched comparison (1.55cm/month [95%CI: 0.98, 2.12]). Among this sample of BAN-exited children, early weaning was associated with dietary deficiencies and girls experienced reduced growth velocity. In resource-poor settings, HIV prevention programs must ensure that breastfeeding stop only once a nutritionally adequate and safe diet without breastmilk can be provided