Beth Carlton Tohill

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.

Vaginal flora morphotypic profiles and assessment of bacterial vaginosis in women at risk for HIV infection.

Specific morphotypic profiles of normal and abnormal vaginal flora, including bacterial vaginosis (BV), were characterized. A prospective study of 350 women yielded concurrent Gram-stain data and clinical assessment (n = 3455 visits). Microbiological profiles were constructed by Gram stain. Eight profile definitions were based on dichotomizing the levels of Lactobacillus, Gardnerella, and curved, Gram-negative bacillus (Mobiluncus) morphotypes. Of these, two were rare, and the other six demonstrated a graded association with the clinical components of BV. The proposed profiles from the Gram stain reflect the morphotypic categories describing vaginal flora that may enable clearer elucidation of gynecologic and obstetric outcomes in various populations.

Reductions in Dietary Energy Density as a Weight Management Strategy

Reducing caloric intake is the cornerstone of dietary therapy for long-term healthy weight management. Strategies individuals have typically used include limiting portion sizes, food groups, or certain macronutrients. Although such restrictive approaches can lead to weight loss in the short term, they can result in feelings of hunger or dissatisfaction, which can limit their acceptability, sustainability, and long-term effectiveness. An alternative positive strategy to manage energy intake is for individuals to eat more foods that are low in calories for a given measure of food—that is, they are low in energy density (kcal/g). Data have shown that people eat a fairly consistent amount of food on a day-to-day basis; therefore, the energy density of the foods an individual consumes influences energy intake. Encouraging patients to eat more foods low in energy density and to substitute these foods for those higher in energy density allows them to decrease their energy intake while eating sati sfying portions, thereby controlling hunger and lowering energy intake. This type of diet fi ts with the current Dietary Guidelines for Americans in that it incorporates high quantities of fruits, vegetables, and fiber, which are often suboptimal in typical low-calorie diets, and it provides ample intakes of numerous micronutrients. Moreover, studies have found that individuals who consume lower-energy-dense diets consume more food by weight and have lower body weights compared with individuals who consume higher-energy-dense diets. This chapter reviews the evidence supporting the use of diets rich in low-energy-dense foods for weight management and provides practical approaches to lowering the energy density of the diet.