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BACKGROUND Control of the pediatric HIV epidemic is hampered by gaps in diagnosis and linkage to effective treatment. The 2015-2016 Malawi Population-based HIV impact assessment data were analyzed to identify gaps in pediatric HIV diagnosis, treatment, and viral load suppression. METHODS In half of the surveyed households, children ages ≥18 months to

Transitions between services for continued antiretroviral treatment (ART) during and after pregnancy are a commonly overlooked aspect of the HIV care cascade, but ineffective transitions can lead to poor health outcomes for women and their children. In this qualitative study, we conducted interviews with 15 key stakeholders from Ministries of Health along with PEPFAR-supported and other in-country non-governmental organizations actively engaged in national programming for adult HIV care and prevention of mother-to-child-transmission of HIV (PMTCT) services in Côte d’Ivoire, Lesotho and Malawi. We aimed to understand perspectives regarding transitions into and out of PMTCT services for continued ART. Thematic analysis revealed that, although transitions of care are necessary and a potential point of loss from ART care in all three countries, there is a lack of clear guidance on transition approach and no formal way of monitoring transition between services. Several opportunities were identified to monitor and strengthen transitions of care for continued ART along the PMTCT cascade.

Background Malawi spearheaded the development and implementation of Option B+ for prevention of mother-to-child transmission of HIV (PMTCT), providing life-long ART for all HIV-positive pregnant and breastfeeding women. We used data from the 2015–2016 Malawi Population-based HIV Impact Assessment (MPHIA) to estimate progress toward 90-90-90 targets (90% of those with HIV know their HIV-positive status; of these, 90% are receiving ART; and of these, 90% have viral load suppression [VLS]) for HIV-positive women reporting a live birth in the previous 3 years. Methods MPHIA was a nationally representative household survey; consenting eligible women aged 15–64 years were interviewed on pregnancies and outcomes, including HIV status during their most recent pregnancy, PMTCT uptake, and early infant diagnosis (EID) testing. Descriptive analyses were weighted to account for the complex survey design. Viral load (VL) results were categorized by VLS ( Results Of the 3,153 women included in our analysis, 371 (10.1%, 95% confidence interval [CI]: 8.8%–11.3%) tested HIV positive in the survey. Most HIV-positive women (84.2%, 95% CI: 79.9%–88.6%) reported knowing their HIV-positive status; of these, 94.9% (95% CI: 91.7%–98.2%) were receiving ART; and of these, 91.2% (95% CI: 87.4%–95.0%) had VLS. Among the 371 HIV-positive women, 76.0% (95% CI: 70.4%–81.7%) had VLS and 66.5% (95% CI: 59.8%–73.2%) had undetectable VL. Among 262 HIV-exposed children, 50.8% (95% CI: 42.8%–58.8%) received EID testing within 2 months of birth, whereas 17.9% (95% CI: 11.9%–23.8%) did not receive EID testing. Of 190 HIV-exposed children with a reported HIV test result, 2.1% (95% CI: 0.0%–4.6%) had positive results. Conclusions MPHIA data demonstrate high PMTCT uptake at a population level. However, our results identify some gaps in VLS in postpartum women and EID testing.

Cotrimoxazole preventive therapy may lead to fewer prescriptions., Antimicrobial drug resistance is a serious health hazard driven by overuse. Administration of antimicrobial drugs to HIV-exposed, uninfected infants, a population that is growing and at high risk for infection, is poorly studied. We therefore analyzed factors associated with antibacterial drug administration to HIV-exposed, uninfected infants during their first year of life. Our study population was 2,152 HIV-exposed, uninfected infants enrolled in the Breastfeeding, Antiretrovirals and Nutrition study in Lilongwe, Malawi, during 2004–2010. All infants were breastfed through 28 weeks of age. Antibacterial drugs were prescribed frequently (to 80% of infants), and most (67%) of the 5,329 prescriptions were for respiratory indications. Most commonly prescribed were penicillins (43%) and sulfonamides (23%). Factors associated with lower hazard for antibacterial drug prescription included receipt of cotrimoxazole preventive therapy, receipt of antiretroviral drugs, and increased age. Thus, cotrimoxazole preventive therapy may lead to fewer prescriptions for antibacterial drugs for these infants.

OBJECTIVE: To describe maternal and neonatal morbidity and mortality among women with HIV infection and their infants. METHODS: A secondary analysis was undertaken of data obtained in the BAN Study a trial of postnatal antiretrovirals among pregnant women with HIV infection enrolled in 2004-2010. Mothers and infants had 13 scheduled visits through 48 weeks of follow-up. Serious maternal morbidity and mortality were examined at delivery (n=2791) from delivery to 6 weeks later (n=2369) and from 7 to 48 weeks (n=1980). Neonatal morbidity and mortality were examined (n=2685). RESULTS: Of 2791 deliveries 169 (6.1%) were by cesarean (153 emergency). Compared with women with vaginal delivery those with cesarean delivery had lower prenatal HIV viral loads (P=0.016) and increased odds of pre-eclampsia/eclampsia (odds ratio [OR] 10.8 95% CI 4.4-26.8). Women with cesarean delivery also had increased odds of serious infection with 14 days of delivery (OR 3.0 95% CI 1.3-7.4) and severe anemia (grade 3 or 4) by 6 weeks (OR 6.7 95% CI 2.3-19.1). Infants born by cesarean had increased odds of a low 5-minute Apgar score (OR 8.1 95% CI 3.5-18.6) and admission to an intensive care unit (OR 5.4 95% CI 3.7-7.8). CONCLUSION: Odds of serious maternal and neonatal morbidity were higher after cesarean than vaginal delivery despite lower maternal viral loads. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

BACKGROUND Antiretroviral (ARV) interventions are used to reduce HIV viral replication and prevent mother-to-child transmission. Viral suppression relies on adherence to ARVs. METHODS A 2-phase study was conducted using data from the Breastfeeding, Antiretrovirals, and Nutrition study. We included mothers randomized to 28 weeks of postpartum ARVs with ≥1 plasma or breastmilk specimen. All mothers who transmitted HIV to their infants from 2-28 weeks (n = 31) and 15% of mothers who did not (n = 232) were included. Adherence was measured by pill count [categorized as poor (0%-80%), partial (81%-98%), and near perfect (>98%)]. Associations between adherence and breastmilk RNA were assessed using mixed-effects models. Cox models were used to estimate associations between breastmilk RNA and HIV transmission. Using Monte Carlo simulation, we estimated the number of transmissions that would occur had everyone randomized to maternal ARVs been 90% and 100% adherent. RESULTS Partial or near perfect ARV adherence significantly reduced the odds of having detectable (≥40 copies/mL) breastmilk RNA, compared with poor adherence (Odds Ratio (OR) 0.23, 95% CI: 0.08 to 0.67; OR 0.36, 95% CI: 0.16 to 0.81, respectively). Detectable breastmilk RNA was associated with increased breastmilk transmission compared with undetectable breastmilk RNA (hazard ratio 3.8, 95% CI: 1.2 to 12.1). All transmitting mothers had ≥1 plasma viral load specimen >100 copies per milliliter. An estimated similar number of transmissions would occur with 90% adherence compared with 100%. CONCLUSIONS Helping patients adhere to ARVs throughout breastfeeding is important for realizing the full potential of recommended ARV interventions to prevent mother-to-child HIV transmission. Maintaining plasma viral load

The World Health Organization (WHO) recommends that all human immunodeficiency virus (HIV)–exposed infants begin cotrimoxazole preventive therapy (CPT) between 4 and 6 weeks of age, and continue CPT until at least 6 weeks after cessation of breastfeeding and until HIV infection has been ruled out [1]. CPT is used to avoid often-fatal opportunistic infections among children born to HIV-infected women, and in turn reduces hospital admissions. CPT use among HIV-infected adults and children has been associated with reductions in malaria incidence, as cotrimoxazole has antimalarial activity [2–4]. Similarly, CPT has been associated with reduced incidence of clinical malaria among HIV-exposed but uninfected (HEU) infants, with some suggestion that protective benefits may wane over time [5–7]. As early infant HIV diagnosis services are becoming more widely available in Africa, and as more efficacious drug regimens for the prevention of mother-to-child HIV transmission are being adopted and extended throughout the breastfeeding period, the population of HEU infants is growing. A better understanding of the impact of CPT on malaria among HEU infants is needed. To date, only clinical or symptomatic malaria has been examined in studies of CPT use and malaria incidence. However, clinical malaria represents only a portion of all malaria infections, as many malaria infections are asymptomatic. Although asymptomatic infections are more common in older children, they do occur in infants. We assessed the association between CPT and a composite outcome of clinical or asymptomatic infection. Additionally, we evaluated the association between CPT and both clinical and asymptomatic infections separately. Including asymptomatic infection adds valuable information concerning the routine use of CPT among the growing population of HEU infants, as the role of asymptomatic parasitemia in malaria transmission has garnered increasing attention. Although density of parasitemia and gametocytemia affects transmission efficiency [8], transmission may occur from asymptomatic patients and patients with submicroscopic parasitemia [9]. In addition to assessing the impact of CPT on malaria infection, we also compared characteristics of the asymptomatic infections by CPT status. Specifically, we assessed (1) parasitemia levels; (2) complexity of individual infections, as in high-transmission areas such as Malawi infections are often polyclonal; and (3) frequency of single-nucleotide polymorphisms in dhfr and dhps, the genes associated with resistance to antifolate antimalarials. Because resistance to antifolate antimalarials is common in Africa, understanding how CPT affects parasite characteristics and works in the presence of high levels of antifolate resistance is important.

Objective:Estimate association between postpartum antiretroviral adherence and breast milk HIV-1 transmission.Design:Prospective cohort study.Methods:Mother–infant pairs were randomized after delivery to immediately begin receiving 28 weeks of either triple maternal antiretrovirals (zidovudine, lami

Background: Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants. Objective: We tested the effects of lipid-based nutrient supplements (LNS) that contained 1.3 times the Recommended Dietary Allowance of sodium selenite and antiretroviral drugs (ARV) on maternal plasma and breast-milk selenium concentrations. Design: HIV-infected Malawian mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomly assigned at delivery to receive: LNS, ARV, LNS and ARV, or a control. In a subsample of 526 mothers and their uninfected infants, we measured plasma and breast-milk selenium concentrations at 2 or 6 (depending on the availability of infant samples) and 24 wk postpartum. Results: Overall, mean (6SD) maternal (range: 81.2 6 20.4 to 86.2 6 19.9 mg/L) and infant (55.6 6 16.3 to 61.0 6 15.4 mg/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 6 11.5 to 9.8 6 7.3 mg/L) from 2 or 6 to 24 wk postpartum (all P , 0.001). Compared with the highest baseline selenium tertile, low and middle tertiles were positively associated with a change in maternal plasma or breast-milk selenium from 2 or 6 to 24 wk postpartum (both P , 0.001). With the use of linear regression, we showed that LNS that contained selenium and ARV were not associated with changes in maternal plasma and breast-milk selenium, but maternal selenium concentrations were positively associated with infant plasma selenium at 2 or 6 and 24 wk postpartum (P , 0.001) regardless of the study arm. Conclusions: Selenite supplementation of HIV-infected Malawian women was not associated with a change in their plasma or breast-milk selenium concentrations. Future research should examine effects of more readily incorporated forms of selenium (ie, selenomethionine) in HIV-infected breastfeeding women. This trial was registered at clinicaltrials.gov as NCT00164736. Am J Clin Nutr 2014;99:950–6.

Background & Aims The extent of HBV infection to infants of HBV/HIV-coinfected pregnant women in sub-Saharan Africa is unknown. The aim of this study was to assess prevalence of HBV infection among antiretroviral-naive, HIV-infected pregnant women in Malawi and examine HBV transmission to their infants. Methods Plasma from 2048 HIV-infected, Malawian women and their infants were tested for markers of HBV infection. Study participants were provided standard-of-care health services, which included administration of pentavalent vaccine to infants at 6, 10, and 14weeks of age. Results One-hundred and three women (5%) were HBsAg-positive; 70 of these HBsAg-positive women were also HBV-DNA-positive. Sixteen women (0.8%) were HBV-DNA-positive but HBsAg-negative. Five of 51 infants (9.8%) born to HBsAg-positive and/or HBV-DNA-positive women were HBV-DNA-positive by 48weeks of age.HBV DNA concentrations of two infants of mothers who received extended lamivudine-containing anti-HIV prophylaxis were 10 IU/ml compared to ⩾8 log 10 IU/ml in three infants of mothers who did not. Conclusions HBV DNA was detected in nearly 10% of infants born to HBV/HIV-coinfected women. Antenatal testing for HIV and HBV, if instituted, can facilitate implementation of prophylactic measures against infant infection by both viruses.

Maternal weight loss during exclusive breastfeeding may influence the growth of exclusively breast-fed infants through impaired quality or quantity of breast milk. This study evaluated how maternal weight loss from 2 to 24 wk postpartum was related to infant weight and length gain in 1309 lactating HIV-infected mothers and their exclusively breast-fed infants. Malawian mother-infant pairs in the Breastfeeding, Antiretrovirals, and Nutrition Study were randomized with a 2 × 3 factorial design to a 2-arm nutritional intervention with a lipid-based nutrient supplement (LNS), meeting nutritional needs of lactation, or no LNS and a 3-arm antiretroviral (ARV) intervention (maternal, infant, or no ARV regimen). Linear regression models were used to relate maternal weight loss (weight loss vs. no weight loss) to infant weight and length gain from birth to 24 mo, stratifying by gender and controlling for maternal BMI at 2 wk (mean ± SD: 23.2 ± 3.0 kg/m(2)) and interacting maternal BMI with weight loss. In adjusted models, compared with daughters of women who did not lose weight, length and weight gain were lower in daughters whose mothers had a lower BMI at 2 wk postpartum coupled with the weight loss. For example, among mothers with an initial BMI of 18 kg/m(2), daughters of those who lost weight gained less weight [β = -0.29 kg (95% CI: -0.53, -0.06)] and length [β = -0.88 cm (95% CI: -1.52, -0.23)] from birth to 24 wk than daughters of those who gained weight. Though effects were only observed in girls, suggesting possible gender differences in suckling and feeding behavior, these findings indicate that maternal weight loss with low energy reserves represents a risk factor for poor infant growth outcomes.

The majority of breast-fed infants of mothers infected with human immunodeficiency virus type 1 (HIV) remain uninfected despite ingesting liters of HIV-containing breast milk over several months [1]. The mechanisms of protection from infection and transmission are incompletely understood. In particular, much remains to be learned about the role of mucosal barriers and the innate and adaptive immune responses that defend infants against mucosal HIV transmission. Increased intestinal permeability may be one of the mechanisms facilitating HIV transmission through breast-feeding. In young infants, as the intestinal barrier matures, the tight junctions between enterocytes close and intestinal permeability decreases [2]. Gastrointestinal infections and malnutrition disrupt this maturational process and increase intestinal permeability, as does artificial (ie, formula) feeding [3]. This mechanism may account for the higher risk of HIV infection with mixed feeding, compared with exclusive breast-feeding [4]. A study showed that African infants displayed increasing intestinal permeability after 3 months of life, contrary to European infants, and by 12 months of life intestinal permeability was 5 times as high in African infants, compared with European infants [5]. Traditionally, assays to evaluate intestinal permeability have been based on differential absorption of carbohydrates (such as the lactulose-mannitol assay) [3, 5]. Such assays are cumbersome and time intensive, particularly for infants. The intestinal epithelium acts as a barrier to luminal contents, including bacteria and endotoxins. Injuries to the intestinal barrier result in bacterial or endotoxin translocation from the intestinal lumen to the systemic circulation through the intestinal mucosa, in the absence of overt bacteremia [6]. This process is termed microbial translocation, and it can be quantified by measuring plasma levels of lipopolysaccharide (LPS), an endotoxin and component of gram-negative bacteria [6–8]. Intestinal permeability, measured by the lactulose-mannitol test, and systemic endotoxemia, measured by detection of LPS by the Limulus amebocyte lysate assay, showed a significant positive correlation in one study [6]. Elevated plasma LPS levels are indicative of disrupted intestinal mucosal integrity and can occur after invasive gastrointestinal surgery, in graft-versus-host disease, and in inflammatory bowel disease, as well as in HIV infection [6, 9–11]. LPS is a potent stimulator of macrophages, monocytes, and neutrophils and causes release of cytokines that are inflammatory mediators [11, 12]. We postulated that microbial translocation through the gut, a marker of disrupted intestinal mucosal integrity, may correlate with increased risk of acquisition of HIV infection through breast-feeding. We tested this hypothesis with samples from the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study, a large prospectively followed cohort of breast-fed infants born to HIV-infected mothers. We studied plasma LPS levels and cellular and soluble markers of immune activation at various times during infants’ first year of life to determine the dynamics of microbial translocation through the gut and examine its relationship with feeding pattern (ie, breast-feeding vs weaned status), receipt of antibiotic prophylaxis, and infants' nutritional status; to explore the correlation of microbial translocation with cellular and soluble markers of immune activation; and to determine the role of microbial translocation in acquisition of HIV infection through breast-feeding.

Background Human immunodeficiency virus (HIV)-exposed infants are disproportionately at risk of morbidity and mortality compared with their HIV-unexposed counterparts. The role of co-trimoxazole preventive therapy (CPT) in reducing leading causes of infectious morbidity is unclear. Methods We used data from the Breastfeeding, Antiretrovirals and Nutrition (BAN) clinical trial (conducted 2004-2010, Malawi) to assess the association of (1) CPT and (2) asymptomatic malaria parasitemia with respiratory and diarrheal morbidity in infants. In June 2006, all HIV-exposed infants in BAN began receiving CPT (240 mg) from 6 to 36 weeks of age, or until weaning occurred and HIV infection was ruled out. All HIV-exposed, uninfected infants (HEIs) at 8 weeks of age (n = 1984) were included when CPT was the exposure. A subset of HEIs (n = 471) were tested for malarial parasitemia using dried blood spots from 12, 24, and 36 weeks of age. Cox proportional hazards models for recurrent gap-time data were used to examine the association of time-varying exposures on morbidity. Results CPT was associated with a 36% reduction in respiratory morbidity (hazard ratio [HR], 0.64 [95% confidence interval {CI}, .60-.69]) and a 41% reduction in diarrheal morbidity (HR, 0.59 [95% CI, .54-.65]). Having asymptomatic malaria parasitemia was associated with a 40% increase in respiratory morbidity (HR, 1.40 [95% CI, 1.13-1.74]) and a 50% increase in diarrheal morbidity (HR, 1.50 [95% CI, 1.09-2.06]), after adjusting for CPT. Conclusions CPT may have an important role to play in reducing the leading global causes of morbidity and mortality in the growing population of HEIs in malaria-endemic resource-limited settings.

Background 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.

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/mm(3), hemoglobin ≥70 g/L, and BMI ≥17 kg/m(2) 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/m(2)) 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.

Background: Breastfeeding increases metabolic demands on the mother, and excessive postnatal weight loss increases maternal mortality. Objective: We evaluated the efficacy of a lipid-based nutrient supplement (LNS) for prevention of excess weight loss in breastfeeding, HIV-infected women. Design: The BAN (Breastfeeding, Antiretrovirals, and Nutrition) Study was a randomized controlled trial in Lilongwe, Malawi. At delivery, HIV-infected mothers and their infants were randomly assigned according to a 2-arm (with and without LNS) by 3-arm (maternal triple-antiretroviral prophylaxis, infant-nevirapine prophylaxis, or neither) factorial design. The 28-wk LNS intervention provided daily energy (700 kcal), protein (20 g), and micronutrients (except for vitamin A) to meet lactation needs. Women were counseled to breastfeed exclusively for 24 wk and to wean by 28 wk. Weight change (0‐28 wk) was tested in an intent-to-treat analysis by using 2-factor ANOVA and with longitudinal mixed-effects models. Results: At delivery, the LNS (n = 1184) and control (n = 1185) groups had similar mean weights and BMIs. Women receiving the LNS had less 0‐28-wk weight loss (21.97 compared with 22.56 kg, P = 0.003). This difference remained significant after adjustment for maternal antiretroviral drug therapy and baseline BMI. Women receiving antiretroviral drugs had more weight loss than did those not receiving antiretroviral drugs (22.93 compared with 21.90 kg, P , 0.001). The benefit of the LNS for reducing weight loss was observed both in those receiving antiretroviral drugs (22.56 compared with 23.32 kg, P = 0.019) and in those not receiving antiretroviral drugs (21.63 compared with 22.16 kg, P = 0.034). Conclusions: The LNS reduced weight loss among HIV-infected, breastfeeding women, both in those taking maternal antiretroviral prophylaxis to prevent postnatal HIV transmission and in those not receiving antiretroviral prophylaxis. Provision of an LNS may benefit HIV-infected, breastfeeding women in resource-limited settings. This trial was registered at clinicaltrials.gov as NCT00164762. Am J Clin Nutr 2012;95:759‐65.

There are potential health risks associated with the use of early weaning to prevent mother-to-child transmission of human immunodeficiency virus (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 with 40 HIV-negative, community children matched on age, gender and local health clinic. Nutrient intake was calculated from 24-h 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 two 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 {0.02 g kg−1 per day [95% confidence interval (CI): 0.01, 0.03]} than their matched comparison [0.05 g kg−1 per day (95% CI: 0.03, 0.07)]; BAN girls grew significantly slower [0.73 cm month−1 (95% CI: 0.40,1.06)] than their matched comparison (1.55 cm month−1[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 programmes must ensure that breastfeeding stop only once a nutritionally adequate and safe diet without breast milk can be provided.

International guidelines recommend exclusive breastfeeding to 6 months among HIV-infected mothers choosing to breastfeed and cessation thereafter if replacement feeding is acceptable, feasible, affordable, sustainable and safe. When mothers wean they are challenged to provide an adequate replacement diet. This study investigates the use and acceptability of a lipid-based nutrient supplement (LNS) as a breastmilk substitute when provided to infants (6-12mo) of HIV-positive mothers, as part of the Breastfeeding, Antiretroviral, and Nutrition (BAN) Study. A sub-sample of mothers (n=45) participated in interviews that explored exclusive breastfeeding, weaning, and strategies to feed LNS. Mothers reported several weaning strategies, including gradual reduction of breastfeeding, expressing breastmilk into a cup, and separation of mother and child. LNS, a peanut-based micronutrient fortified paste, was highly accepted and incorporated into the traditional diet. Weaning is a feasible HIV prevention method among this population in Malawi when supported by the provision of LNS as a breastmilk substitute.

Background Antibiotic resistance is a serious health hazard driven by overuse. Antibiotic usage in low-income countries is poorly studied. HIV-exposed, uninfected (HEU) infants are a growing population at high risk for infection and resulting antibiotic use. Methods We described antibiotic usage among 2,152 HEU infants in the Breastfeeding, Antiretrovirals and Nutrition (BAN) Study in Lilongwe, Malawi, 2004–2010. Factors were tested for associations with antibiotic prescription using a repeated-measures Cox proportional hazards model and included cotrimoxazole preventive therapy (CPT) exposure, malaria season, antiretroviral (ARV) treatment, receipt of maternal nutritional supplement, maternal CD4+ T-cell count, HIV viral load, maternal age, infant sex and birthweight. Results Overall, 80% of HEU infants in the BAN study received an antibiotic prescription during follow-up (median length: 336 days). The majority (67%) of the 5,107 antibiotic prescriptions were for respiratory indications. Penicillins (43%) were the most commonly prescribed type of antibiotics, followed by sulfonamides (23%). The median number of prescriptions received per infant-month was 0.2 (interquartile range (IQR): 0.1, 0.3). Factors associated with lower hazard of antibiotic prescription included CPT exposure (hazard ratio (HR): 0.57 [95% confidence interval (CI): 0.52, 0.61]), maternal ARV (HR: 0.85, 95% CI: [0.78, 0.93]), and infant ARV (HR: 0.90, 95% CI: [0.82, 0.98]). Hazard of antibiotic prescription also decreased as participants aged (HR for ages 6–12 months vs. 0–1 month: 0.48, 95% CI: [0.40, 0.58]). Male sex (HR: 1.09, 95% CI: [1.02, 1.17]) and log maternal viral load (copies/mL) (HR: 1.02, 95% CI: 1.003, 1.04) were associated with increased hazard of antibiotic prescription. Conclusion This study provides an estimate of antibiotic use by HEU infants in a low-income country and evidence that CPT may lead to reduced antibiotic use. Disclosures All authors: No reported disclosures.

A process evaluation of nurses’ implementation of an infant-feeding counseling protocol was conducted for the Breastfeeding, Antiretroviral and Nutrition (BAN) Study, a prevention of mother-to-child transmission of HIV clinical trial in Lilongwe, Malawi. Six trained nurses counseled HIV-infected mothers to exclusively breastfeed for 24 weeks postpartum and to stop breastfeeding within an additional four weeks. Implementation data were collected via direct observations of 123 infant feeding counseling sessions (30 antenatal and 93 postnatal) and interviews with each nurse. Analysis included calculating a percent adherence to checklists and conducting a content analysis for the observation and interview data. Nurses were implementing the protocol at an average adherence level of 90% or above. Although not detailed in the protocol, nurses appropriately counseled mothers on their actual or intended formula milk usage after weaning. Results indicate that nurses implemented the protocol as designed. Results will help to interpret the BAN Study’s outcomes.

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.

BACKGROUND: Cytomegalovirus (CMV) infection can be acquired in utero or postnatally through horizontal transmission and breastfeeding. The effect of postnatal CMV infection on postnatal HIV transmission is unknown. METHODS: The Breastfeeding Antiretrovirals and Nutrition study conducted in Malawi randomized 2369 mothers and their infants to three antiretroviral prophylaxis arms - mother (triple regimen) infant (nevirapine) or neither - for 28 weeks of breastfeeding followed by weaning. Stored plasma and peripheral blood mononuclear cell specimens were available for 492 infants at 24 weeks and were tested with CMV PCR. Available samples from infants who were CMV PCR-positive at 24 weeks were also tested at birth (N = 242) and from infants PCR-negative at 24 weeks were tested at 48 weeks (N = 96). Cox proportional-hazards models were used to determine if CMV infection was associated with infant morbidity mortality or postnatal HIV acquisition. RESULTS: At 24 weeks of age CMV DNA was detected in 345/492 infants (70.1%); the estimated congenital CMV infection rate was 2.3% and the estimated rate of CMV infection at 48 weeks was 78.5%. CMV infection at 24 weeks was associated with subsequent HIV acquisition through breastfeeding or infant death between 24 and 48 weeks of age (hazard ratio 4.27 P = 0.05). CONCLUSION: Most breastfed infants of HIV-infected mothers in this resource-limited setting are infected with CMV by 24 weeks of age. Early CMV infection may be a risk factor for subsequent infant HIV infection through breastfeeding pointing to the need for comprehensive approaches in order to achieve elimination of breastfeeding transmission of HIV.

In Sub-Saharan Africa, prevalence estimates of hepatitis C virus (HCV) vary widely.To assess the prevalence of HCV infection among HIV-infected, pregnant women screened for a large clinical trial in Lilongwe, Malawi.Plasma from 2041 HIV-infected, pregnant women was screened for anti-HCV IgG using a chemiluminiscent immunometric assay (CIA). Specimens with a signal-cut-off ratio≥1.00 were considered reactive and those with S/Co ratio1.00 non-reactive. All CIA-reactive specimens were tested by a recombinant immunoblot assay (RIBA) for anti-HCV and by PCR for HCV RNA.Of 2041 specimens, 110 (5.3%, 95% CI: 4.5-6.5%) were CIA reactive. Of the 109 CIA reactive specimens available for RIBA testing, 2 (1.8%) were positive, 28 (25.7%) were indeterminate, and 79 (72.5%) were negative. All CIA-reactive specimens were HCV RNA negative (n=110). The estimated HCV prevalence based on the screening assay alone was 5.3%; based on supplemental RIBA testing, the status of HCV infection remained indeterminate in 1.4% (28/2040, 95% CI: 0.1-2.0) and the prevalence of confirmed HCV infections was 0.1% (2/2040, 95% CI: 0-0.4%).HCV seroprevalence among HIV-infected, pregnant women in Malawi confirmed by supplemental RIBA HCV 3.0 is low (0.1%); CIA showed a high false-reactivity rate in this population.

In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their infants (through fetal iron accretion) may be at risk of iron deficiency. We assessed the effects of maternal micronutrient-fortified lipid-based nutrient supplements (LNS) and maternal ARV treatment or infant ARV prophylaxis on maternal and infant iron status during exclusive breastfeeding from birth to 24 weeks.The Breastfeeding, Antiretrovirals, and Nutrition study was a randomized controlled trial conducted in Lilongwe, Malawi, from 2004 to 2010. HIV-infected mothers (CD4200 cells/μL) and their infants were randomly assigned to 28-week interventions: maternal LNS/maternal ARV (n = 424), maternal LNS/infant ARV (n = 426), maternal LNS (n = 334), maternal ARV (n = 425), infant ARV (n = 426), or control (n = 334). Longitudinal models tested intervention effects on hemoglobin (Hb). In a subsample (n = 537) with multiple iron indicators, intervention effects on Hb, transferrin receptors (TfR), and ferritin were tested with linear and Poisson regression.In longitudinal models, LNS effects on maternal and infant Hb were minimal. In subsample mothers, maternal ARVs were associated with tissue iron depletion (TfR8.3 mg/L) (risk ratio: 3.1, P0.01), but not in ARV-treated mothers receiving LNS (P = 0.17). LNS without ARVs was not associated with iron deficiency or anemia (P0.1). In subsample infants, interventions were not associated with impaired iron status (all P0.1).Maternal ARV treatment with protease inhibitors is associated with maternal tissue iron depletion; but LNS mitigates adverse effects. ARVs do not seem to influence infant iron status; however, extended use needs to be evaluated.

OBJECTIVE The objective of this study is to assess nevirapine (NVP) resistance in infants who became infected in the three arms of the Breastfeeding, Antiretrovirals and Nutrition (BAN) study: daily infant NVP prophylaxis, triple maternal antiretrovirals or no extra intervention for 28 weeks of breastfeeding. DESIGN A prospective cohort study. METHODS The latest available plasma or dried blood spot specimen was tested from infants who became HIV-positive between 3 and 48 weeks of age. Population sequencing was used to detect mutations associated with reverse transcriptase inhibitor resistance. Sequences were obtained from 22 out of 25 transmissions in the infant-NVP arm, 23 out of 30 transmissions in the maternal-antiretroviral arm and 33 out of 38 transmissions in the control arm. RESULTS HIV-infected infants in the infant-NVP arm were significantly more likely to have NVP resistance than infected infants in the other two arms of the trial, especially during breastfeeding through 28 weeks of age (56% in infant-NVP arm vs. 6% in maternal-antiretroviral arm and 11% in control arm, P¼0.004). There was a nonsignificant trend, suggesting that infants with NVP resistance tended to be infected earlier and exposed to NVP while infected for a greater duration than infants without resistance. CONCLUSION Infants on NVP prophylaxis during breastfeeding are at a reduced risk of acquiring HIV, but are at an increased risk of NVP resistance if they do become infected. These findings point to the need for frequent HIV testing of infants while on NVP prophylaxis, and for the availability of antiretroviral regimens excluding NVP for treating infants who become infected while on such a prophylactic regimen.

Background/Aims 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 rates have been reported. In this article, we describe the effectiveness of methods used to encourage retention in the Breastfeeding, Antiretrovirals, and Nutrition study and analyze factors associated with lost to follow-up in the study. Methods The Breastfeeding, Antiretrovirals, and Nutrition clinical trial was designed to evaluate the efficacy of three different mother-to-child HIV transmission prevention strategies. Lower than expected participant retention prompted enhanced efforts to reduce lost to follow-up during the conduct of the trial. Following study completion, we employed regression modeling to determine predictors of perfect attendance and variables associated with being lost to follow-up. Results During the study, intensive tracing efforts were initiated after the first 1686 mother–infant pairs had been enrolled, and 327 pairs were missing. Of these pairs, 60 were located and had complete data obtained. Among the 683 participants enrolling after initiation of intensive tracing efforts, the lost to follow-up rate was 3.4%. At study’s end, 290 (12.2%) of the 2369 mother–infant pairs were lost to follow-up. Among successfully traced missing pairs, relocation was common and three were deceased. Log-binomial regression modeling revealed higher maternal hemoglobin and older maternal age to be significant predictors of perfect attendance. These factors and the presence of food insecurity were also significantly associated with lower rates of lost to follow-up. Conclusion In this large HIV prevention trial, intensive tracing efforts centered on reaching study participants at their homes succeeded in finding a substantial proportion of lost to follow-up participants and were very effective in preventing further lost to follow-up during the remainder of the trial. The association between food insecurity and lower rates of lost to follow-up is likely related to the study’s provision of nutritional support, including a family maize supplement, which may have contributed to patient retention.

We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 (HIV-1) in Malawi.We randomly assigned 2369 HIV-1-positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the Kaplan-Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1-negative 2 weeks after birth. Rates were compared with the use of the log-rank test.Among mother-infant pairs, 5.0% of infants were HIV-1-positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P=0.009) or the infant-regimen group (1.7%, P0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P=0.02), and 2.6% in the infant-regimen group (P0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction.The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736.)

Infant iron status at birth is influenced by maternal iron status during pregnancy; however, there are limited data on the extent to which maternal iron status is associated with infant iron status during exclusive breastfeeding. We evaluated how maternal and infant hemoglobin and iron status [soluble transferrin receptors (TfR) and ferritin] were related during exclusive breastfeeding in HIV-infected women and their infants. The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial in Lilongwe, Malawi, in which HIV-infected women were assigned with a 2 × 3 factorial design to a lipid-based nutrient supplement (LNS), or no LNS, and maternal, infant, or no antiretroviral drug, and followed for 24 wk. Longitudinal models were used to relate postpartum maternal hemoglobin (n = 1926) to concurrently measured infant hemoglobin, adjusting for initial infant hemoglobin values. In a subsample, change in infant iron status (hemoglobin, log ferritin, log TfR) between 2 (n = 352) or 6 wk (n = 167) and 24 wk (n = 519) was regressed on corresponding change in the maternal indicator, adjusting for 2 or 6 wk values. A 1 g/L higher maternal hemoglobin at 12, 18, and 24 wk was associated with a 0.06 g/L (P = 0.01), 0.10 g/L (P < 0.001), and 0.06 g/L (P = 0.01), respectively, higher infant hemoglobin. In the subsample, a reduction in maternal log TfR and an increase in hemoglobin from initial measurement to 24 wk were associated with the same pattern in infant values (log TfR β = −0.18 mg/L, P < 0.001; hemoglobin β = 0.13 g/L, P = 0.01). Given the observed influence of maternal and initial infant values, optimizing maternal iron status in pregnancy and postpartum is important to protect infant iron status. This trial was registered at clinicaltrials.gov as NCT00164736.

Background An intensive, prospective, open-label pharmacokinetic (PK) study in a subset of HIV-infected mothers and their uninfected infants enrolled in the Breastfeeding, Antiretroviral and Nutrition (BAN) Study was performed to describe drug exposure and antiviral response. Methods Women using Combivir® (zidovudine [ZDV] + lamivudine [3TC]) + Aluvia® (lopinavir/ritonavir [LPV/ RTV]) were enrolled. Breast milk (BM), mother plasma (MP) and infant plasma (IP) samples were obtained over 6 h after observed dosing at 6, 12 or 24 weeks post-partum for drug concentrations and HIV RNA. Results A total of 30 mother/infant pairs (10 each at 6, 12 and 24 weeks post-partum) were enrolled. Relative to MP, BM concentrations of ZDV and 3TC were 35% and 21% higher, respectively, whereas LPV and RTV were 80% lower. Only 3TC was detected in IP with concentrations 96% and 98% lower than MP and BM, respectively. Concentrations in all matrices were similar at 6–24 weeks. The majority (98.3%) of BM concentrations were >HIVwt IC50, with one having detectable virus. There was no association between PK parameters and MP or BM HIV RNA. Conclusions ZDV and 3TC concentrated in BM whereas LPV and RTV did not, possibly due to protein binding and drug transporter affinity. Undetectable to low antiretroviral concentrations in IP suggest prevention of transmission while breastfeeding may be due to antiretroviral effects on systemic or BM HIV RNA in the mother. Low IP 3TC exposure may predispose an infected infant to HIV resistance, necessitating testing and treating infants early.

OBJECTIVES: To evaluate severe (grade 3/4) morbidity and mortality in HIV-exposed uninfected infants. DESIGN: : Secondary data analysis of The Breastfeeding Antiretrovirals and Nutrition (BAN) clinical trial. METHODS: BAN randomized 2369 mother-infant pairs to maternal infant or no extended antiretroviral prophylaxis during breastfeeding. Morbidity outcomes examined were pneumonia/serious febrile illness diarrhea/growth faltering and malaria. Infant death was defined as neonatal (

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 < 0.001) and LAZ (−0.93 to −1.56 SD; P < 0.001) steadily declined, whereas BMIZ remained >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.

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 trial to evaluate antiretroviral and nutrition interventions to reduce mother-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/week, from baseline (12 to 30 weeks gestation) until the last follow-up visit (32–38 weeks). 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 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.

Naturally occurring low white-cell counts may be associated with an increased risk of mother-to-child transmission of HIV.