Issues in the design of a clinical trial with a behavioral intervention—the Zambia exclusive breast-feeding study Donald M. Thea a, * , Cheswa Vwalika b , Prisca Kasonde c , Chipepo Kankasa c , Moses Sinkala c , Katherine Semrau a , Erin Shutes d , Christine Ayash a , Wei-Yann Tsai e , Grace Aldrovandi d , Louise Kuhn f a Center for International Health and Development, Boston University School of Public Health, 710 Albany Street, 715, Boston, MA 02118, USA b Lusaka District Health Management Team, Lusaka, Zambia, South Africa c University Teaching Hospital, University of Zambia, Lusaka, Zambia, South Africa d Rollins School of Public Health, Emory University, Atlanta, GA, USA e Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA f Gertrude H. Sergievsky Center, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA Received 15 January 2004; accepted 4 June 2004 Abstract Purpose: We present the rationale and design of the Zambian Exclusive Breast-feeding Study (ZEBS), a randomized trial evaluating the efficacy of short-duration exclusive breast-feeding (EBF) as a strategy to reduce postnatal human immunodeficiency virus (HIV) transmission while preserving the other health benefits of this important mode of infant feeding. Methods: One thousand two hundred HIV-positive pregnant women were recruited in Lusaka, Zambia, and followed with their infants for 24 months. In addition to Nevirapine (NVP), all women received intensive and frequent clinic- and home-based counseling to support exclusive breast-feeding. When the infant was 1 week of age, half of the women were randomly assigned to a group encouraged to abruptly ( < 24 h) cease all breast-feeding at 4 months. The primary outcome of the experimental (randomized) comparison is HIV-free survival at 24 months. The design is also observational and will compare HIV transmission rates between those who do and do not adhere to the counseling intervention promoting exclusive breast-feeding. Conclusion: Our study aims to quantify the benefit –risk ratio of early cessation of exclusive breast-feeding to interrupt mother-to-child transmission of HIV with an intensive behavioral intervention and has both observational and experimental analytic approaches. Our study design assesses efficacy and also has a 0197-2456/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.cct.2004.06.005 * Corresponding author. Tel.: +1-617-414-1271; fax: +1-617-414-1261. E-mail address: dthea@bu.edu (D.M. Thea). www.elsevier.com/locate/conclintrial Controlled Clinical Trials 25 (2004) 353 – 365