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

Abstract

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, ongoing, randomized breastfeeding intervention trial of HIVinfected 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.

Antiretroviral therapy provided to HIV-infected Malawian women in a randomized trial diminishes the positive effects of lipid-based nutrient supplements on breast-milk B vitamins

“…The recruitment methods and flow of participants have been described in detail elsewhere (8,11,16,17). Mothers in this study were counseled to exclusively breastfeed for 24 wk and then to rapidly wean from 24 to 28 wk, in accordance with WHO recommendations at the time the study began (16,18).…”

“…They were excluded from the subsample if the infants became HIV-positive or were multiple births. The larger study's sample size calculations were previously described in detail (16). As with all food-based nutrition supplement trials, participants and physicians could not be blinded to the study arm.…”

Breastfeeding in HIV-Positive Women

“…[54] The study is expected to be completed in late 2009, with a total enrolment of approximately 1400 mothers and their infants. Pregnant women were enrolled if their CD4+ cell counts were >200 cells mL.…”

Preventing Mother-to-Child Transmission of Hiv in Resource-Limited Settings

“…Strategies need to be developed for making prolonged breastfeeding safer for HIV-infected women who do not have the option of early cessation; these include giving ARV drugs to breastfeeding women to reduce plasma HIV viral load [88][89][90] or to their children as post exposure prophylaxis during breastfeeding [91][92][93]. Challenges associated with these approaches include the costs of providing ARV drugs to women and/or children throughout the breastfeeding period, concerns of developing drug resistance and the prolonged exposure to ART for uninfected children.…”