Ellen G. Piwoz

Early exclusive breastfeeding reduces the risk of postnatal Hiv-1 transmission and increases Hiv-free survival

Objectives:The promotion of exclusive breastfeeding (EBF) to reduce the postnatal transmission (PNT) of HIV is based on limited data. In the context of a trial of postpartum vitamin A supplementation, we provided education and counseling about infant feeding and HIV, prospectively collected information on infant feeding practices, and measured associated infant infections and deaths. Design and methods:A total of 14 110 mother–newborn pairs were enrolled, randomly assigned to vitamin A treatment group after delivery, and followed for 2 years. At baseline, 6 weeks and 3 months, mothers were asked whether they were still breastfeeding, and whether any of 22 liquids or foods had been given to the infant. Breastfed infants were classified as exclusive, predominant, or mixed breastfed. Results:A total of 4495 mothers tested HIV positive at baseline; 2060 of their babies were alive, polymerase chain reaction negative at 6 weeks, and provided complete feeding information. All infants initiated breastfeeding. Overall PNT (defined by a positive HIV test after the 6-week negative test) was 12.1%, 68.2% of which occurred after 6 months. Compared with EBF, early mixed breastfeeding was associated with a 4.03 (95% CI 0.98, 16.61), 3.79 (95% CI 1.40–10.29), and 2.60 (95% CI 1.21–5.55) greater risk of PNT at 6, 12, and 18 months, respectively. Predominant breastfeeding was associated with a 2.63 (95% CI 0.59–11.67), 2.69 (95% CI 0.95–7.63) and 1.61 (95% CI 0.72–3.64) trend towards greater PNT risk at 6, 12, and 18 months, compared with EBF. Conclusion:EBF may substantially reduce breastfeeding-associated HIV transmission.

Child mortality according to maternal and infant HIV status in Zimbabwe

Background: HIV causes substantial mortality among African children but there is limited data on how this is influenced by maternal or infant infection status and timing. Methods: Children enrolled in the ZVITAMBO trial were divided into 5 groups: those born to HIV-negative mothers (NE, n = 9510), those born to HIV-positive mothers but noninfected (NI, n = 3135), those infected in utero (IU, n = 381), those infected intrapartum (IP, n = 508), and those infected postnatally (PN, n = 258). Their mortality was estimated. Results: Two-year mortality was 2.9% (NE infants), 9.2% (NI), 67.5% (IU), 65.1% (IP), and 33.2% (PN). Between 8 weeks and 6 months, mortality in IU infants quintupled (from 309 to 1686/1000 c-y). The median time from infection to death was 208, 380, and >500 days for IU, IP, and PN infants, respectively. Among NI children, advanced maternal disease was predictive of mortality. Acute respiratory infection was the major cause of death. Conclusions: Perinatally infected infants are at particular risk of death between 2 and 6 months: cotrimoxazole prophylaxis and early pediatric HAART should be scaled up. Uninfected infants of infected mothers have at least twice the mortality risk of infants born to uninfected mothers: all HIV-exposed infants should be targeted with child survival interventions. HIV-positive mothers with more advanced disease are not only more likely to infect their infants, but their infants are more likely to die, whether infected or not: provision of antiretroviral treatment to pregnant and lactating women is an urgent need for both mothers and their children.

Modifications of a large HIV prevention clinical trial to fit changing realities: a case study of the Breastfeeding, Antiretroviral, and Nutrition (BAN) protocol in Lilongwe, Malawi.

In order to evaluate strategies to reduce HIV transmission through breast milk and optimize both maternal and infant health among HIV-infected women and their infants, we designed and implemented a large, randomized clinical trial in Lilongwe, Malawi. The development of protocols for large, randomized clinical trials is a complicated and lengthy process often requiring alterations to the original research design. Many factors lead to delays and changes, including study site-specific priorities, new scientific information becoming available, the involvement of national and international human subject committees and monitoring boards, and alterations in medical practice and guidance at local, national, and international levels. When planning and implementing a clinical study in a resource-limited setting, additional factors must be taken into account, including local customs and program needs, language and socio-cultural barriers, high background rates of malnutrition and endemic diseases, extreme poverty, lack of personnel, and limited infrastructure. Investigators must be prepared to modify the protocol as necessary in order to ensure participant safety and successful implementation of study procedures. This paper describes the process of designing, implementing, and subsequently modifying the Breastfeeding, Antiretrovirals, and Nutrition, (BAN) Study, a large, on-going, randomized breastfeeding intervention trial of HIV-infected women and their infants conducted at a single-site in Lilongwe, Malawi. We highlight some of the successes, challenges, and lessons learned at different stages during the conduct of the trial.

Differences between international recommendations on breastfeeding in the presence of HIV and the attitudes and counselling messages of health workers in Lilongwe Malawi.

BackgroundTo prevent postnatal transmission of HIV in settings where safe alternatives to breastfeeding are unavailable, the World Health Organization (WHO) recommends exclusive breastfeeding followed by early, rapid cessation of breastfeeding. Only limited data are available on the attitudes of health workers toward this recommendation and the impact of these attitudes on infant feeding counselling messages given to mothers.MethodsAs part of the Breastfeeding, Antiretroviral, and Nutrition (BAN) clinical trial, we carried out an in-depth qualitative study of the attitudes, beliefs, and counselling messages of 19 health workers in Lilongwe, Malawi.ResultsAlthough none of the workers had received formal training, several reported having counseled HIV-positive mothers about infant feeding. Health workers with counselling experience believed that HIV-infected mothers should breastfeed exclusively, rather than infant formula feed, citing poverty as the primary reason. Because of high levels of malnutrition, all the workers had concerns about early cessation of breastfeeding.ConclusionImportant differences were observed between the WHO recommendations and the attitudes and practices of the health workers. Understanding these differences is important for designing effective interventions.

A lipid-based nutrient supplement mitigates weight loss among HIV-infected women in a factorial randomized trial to prevent mother-to-child transmission during exclusive breastfeeding

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 (-1.97 compared with -2.56 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 (-2.93 compared with -1.90 kg, P < 0.001). The benefit of the LNS for reducing weight loss was observed both in those receiving antiretroviral drugs (-2.56 compared with -3.32 kg, P = 0.019) and in those not receiving antiretroviral drugs (-1.63 compared with -2.16 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.

Uptake of HIV testing and outcomes within a Community-based Therapeutic Care (CTC) programme to treat Severe Acute Malnutrition in Malawi: a descriptive study

BackgroundIn Malawi and other high HIV prevalence countries, studies suggest that more than 30% of all severely malnourished children admitted to inpatient nutrition rehabilitation units are HIV-infected. However, clinical algorithms designed to diagnose paediatric HIV are neither sensitive nor specific in severely malnourished children. The present study was conducted to assess : i) whether HIV testing can be integrated into Community-based Therapeutic Care (CTC); ii) to determine if CTC can improve the identification of HIV infected children; and iii) to assess the impact of CTC programmes on the rehabilitation of HIV-infected children with Severe Acute Malnutrition (SAM).MethodsThis community-based cohort study was conducted in Dowa District, Central Malawi, a rural area 50 km from the capital, Lilongwe. Caregivers and children admitted in the Dowa CTC programme were prospectively (Prospective Cohort = PC) and retrospectively (Retrospective Cohort = RC) admitted into the study and offered HIV testing and counseling. Basic medical care and community nutrition rehabilitation was provided for children with SAM. The outcomes of interest were uptake of HIV testing, and recovery, relapse, and growth rates of HIV-positive and uninfected children in the CTC programme. Students t-test and analysis of variance were used to compare means and Kruskall Wallis tests were used to compare medians. Dichotomous variables were compared using Chi2 analyses and Fishers exact test. Stepwise logistic regression with backward elimination was used to identify predictors of HIV infection (α = 0.05).Results1273 and 735 children were enrolled in the RC and PC. For the RC, the average age (SD) at CTC admission was 30.0 (17.2) months. For the PC, the average age at admission was 26.5 (13.7) months. Overall uptake of HIV testing was 60.7% for parents and 94% for children. HIV prevalence in severely malnourished children was 3%, much lower than anticipated. 59% of HIV-positive and 83% of HIV-negative children achieved discharge Weight-For-Height (WFH) ≥ 80% of the NCHS reference median (p = 0.003). Clinical algorithms for diagnosing HIV in SAM children had poor sensitivity and specificity.ConclusionCTC is a potentially valuable entry point for providing HIV testing and care in the community to HIV infected children with SAM.

Adoption of Safer Infant Feeding and Postpartum Sexual Practices and Their Relationship to Maternal HIV Status and Risk of Acquiring HIV in Zimbabwe

Objective  To examine the relationships between maternal knowledge and concern about HIV status, adoption of preventive practices and risk of acquiring HIV in Zimbabwe.

Human Immunodeficiency Virus Transmission during Breastfeeding

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.

Effects of infant sex on mother-to-child transmission of HIV-1 according to timing of infection in Zimbabwe.

We examined the relationship between sex and the risk of intrauterine, intrapartum and postnatal HIV transmission among 4495 infants born to HIV-infected mothers in Harare, Zimbabwe. Intrauterine transmission was 8.6%, and consistent with other studies was higher among girl than boy infants (AOR 1.53; 95% CI 1.23–1.91). Unlike previous studies, we observed no independent effect of infant sex on intrapartum or breastfeeding-associated HIV transmission. Sex-specific postnatal prevention strategies are not warranted in this population.