• HIV infection detected by 4 months among children with no evidence of HIV infection at birth.
• Survival to 2 years of age without HIV-infection.
• Magnitude of the reduction in mother-to-child HIV transmission and the magnitude of the increase in non-HIV-related under-2-year mortality, attributable to cessation of breastfeeding at 4 months.
• HIV infections detected by 2 years among children with no evidence of HIV infection at 4 months
• Mortality in children aged 4-24 months among uninfected children

The study is designed as a randomized, controlled trial with specific observational objectives. All HIV-seropositive pregnant subjects electing to breastfeed their child will be counselled to exclusively breastfeed through 4 months of age. All live-born children will be randomized (1:1) at birth to one of two counseling programs: A) to encourage abrupt weaning at 4 months of age, or B) to encourage exclusive breastfeeding through 6 months of age with the introduction of typical weaning foods ad lib.

It is well established that infants breast fed by their HIV-infected mothers are at risk of acquiring HIV infection through breast milk. However, in low resource settings, where the HIV epidemic now predominates, breast feeding cannot simply be replaced by breast milk substitutes since alternatives to breast milk are unavailable, unaffordable and unsafe. With this application we aim to test the safety and efficacy of short duration exclusive breast feeding to minimize risks of HIV transmission without increasing risks of non-HIV infant mortality. We propose a 5-year study of HIV-positive mothers and their children to be conducted in two urban primary health care clinics in Lusaka, Zambia. All HIV-positive women and their infants will be offered the two-dose nevirapine intervention and will be counseled about the risks and benefits of infant feeding options. Women who indicate their decision to breast feed will be eligible for enrollment into the study. A culturally appropriate, affordable and sustainable breast feeding education and support program to encourage exclusive breast feeding will be developed, and all women who elect to breast feed will be encouraged to exclusively breast feed to 4 months. Half of the women will be randomized to a counseling program which will encourage abrupt weaning to full replacement feeding at 4 months, and half will be randomized to a program to encourage continued breast feeding after 4 months with the usual introduction of weaning foods. Children will be followed for two years with regular medical histories, physical exams and clinical sampling. The primary objective of the study, based on the random assignment, is to compare HIV transmission rates and under-2 year mortality rates in children who abruptly wean at four months of age versus children who are weaned according to local practice. The second primary objective, based on observational comparisons, is to compare HIV transmission among infants whose mothers adhere to recommendations to exclusively breast feed with those who do not. Secondary objectives are to describe acute and chronic effects of abrupt weaning on child morbidity. The study proposes to test an inexpensive and potentially sustainable public health intervention to reduce HIV transmission through breast feeding while preserving benefits of breast feeding for other aspects of child health in a very low resource setting.

• Albrecht S, Semrau K, Kasonde P, Sinkala M, Kankasa C, Vwalika C, Aldrovandi GM, Thea DM, Kuhn L. Predictors of nonadherence to single-dose nevirapine therapy for the prevention of mother-to-child HIV transmission. J Acquir Immune Defic Syndr. 2006 Jan 1;41(1):114-8.
• Kuhn L, Kasonde P, Sinkala M, Kankasa C, Semrau K, Scott N, Tsai WY, Vermund SH, Aldrovandi GM, Thea DM. Does severity of HIV disease in HIV-infected mothers affect mortality and morbidity among their uninfected infants? Clin Infect Dis. 2005 Dec 1;41(11):1654-61. Epub 2005 Oct 27.
• Kuhn L, Kasonde P, Sinkala M, Kankasa C, Semrau K, Vwalika C, Tsai WY, Aldrovandi GM, Thea DM. Prolonged breast-feeding and mortality up to two years post-partum among HIV-positive women in Zambia. AIDS. 2005 Oct 14;19(15):1677-81.
• Kuhn L, Trabattoni D, Kankasa C, Semrau K, Kasonde P, Lissoni F, Sinkala M, Ghosh M, Vwalika C, Aldrovandi GM, Thea DM, Clerici M. Alpha-defensins in the prevention of HIV transmission among breastfed infants. J Acquir Immune Defic Syndr. 2005 Jun 1;39(2):138-42.
• Semrau K, Kuhn L, Vwalika C, Kasonde P, Sinkala M, Kankasa C, Shutes E, Aldrovandi G, Thea DM. Women in couples antenatal HIV counseling and testing are not more likely to report adverse social events. AIDS. 2005 Mar 24;19(6):603-9.
• Ghosh MK, Kuhn L, West J, Semrau K, Decker D, Thea DM, Aldrovandi GM. Quantitation of human immunodeficiency virus type 1 in breast milk. J Clin Microbiol. 2003 Jun;41(6):2465-70.
• Sabbaj S, Edwards BH, Ghosh MK, Semrau K, Cheelo S, Thea DM, Kuhn L, Ritter GD, Mulligan MJ, Goepfert PA, Aldrovandi GM. Human immunodeficiency virus-specific CD8(+) T cells in human breast milk. J Virol. 2002 Aug;76(15):7365-73.
• Thea DM, Vwalika C, Kasonde P, Kankasa C, Sinkala M, Semrau K, Shutes E, Ayash C, Tsai WY, Aldrovandi G, Kuhn L. Issues in the design of a clinical trial with a behavioral intervention--the Zambia exclusive breast-feeding study. Control Clin Trials. 2004 Aug;25(4):353-65.
• Kuhn L, Aldrovandi GM, Sinkala M, Kankasa C, Semrau K, Kasonde P, Mwiya M, Tsai WY, Thea DM; Zambia Exclusive Breastfeeding Study (ZEBS). Differential effects of early weaning for HIV-free survival of children born to HIV-infected mothers by severity of maternal disease. PLoS One. 2009 Jun 26;4(6):e6059.
• Arpadi S, Fawzy A, Aldrovandi GM, Kankasa C, Sinkala M, Mwiya M, Thea DM, Kuhn L. Growth faltering due to breastfeeding cessation in uninfected children born to HIV-infected mothers in Zambia. Am J Clin Nutr. 2009 Aug;90(2):344-53. Epub 2009 Jun 24.
• Kuhn L, Aldrovandi GM, Sinkala M, Kankasa C, Semrau K, Mwiya M, Kasonde P, Scott N, Vwalika C, Walter J, Bulterys M, Tsai WY, Thea DM; Zambia Exclusive Breastfeeding Study. Effects of early, abrupt weaning on HIV-free survival of children in Zambia. N Engl J Med. 2008 Jul 10;359(2):130-41. Epub 2008 Jun 4.
• Kuhn L, Sinkala M, Kankasa C, Semrau K, Kasonde P, Scott N, Mwiya M, Vwalika C, Walter J, Tsai WY, Aldrovandi GM, Thea DM. High uptake of exclusive breastfeeding and reduced early post-natal HIV transmission. PLoS ONE. 2007 Dec 26;2(12):e1363.

Inclusion Criteria:

• HIV-positive pregnant women identified through VCT
• After counseling about the risks and benefits of feeding alternatives report that it is their intended decision to breastfeed
• Live within the catchment area of George or Chawama clinic
• Are between 30 - 34 wks gestation. (To insure that opportunity exists to receive a minimum of 2 lactation counseling sessions prior to delivery)
• Do not have any significant presenting illness that requires hospitalization
• Agree to adhere to the requirements of study participation (including exclusive breastfeeding and randomization into one of two infant feeding groups at four months).
• Willing to inform a household member (preferably husband/father) of HIV-status.

Exclusion Criteria:

• Lives outside of catchment area;
• Have known major illnesses likely to influence pregnancy outcome including diabetes, severe renal or heart disease, or active tuberculosis, prior to randomization;
• Does not intend to breastfeed;
• Prior enrollment in this study or concurrent enrollment in another study

• US Agency for International Development
• National Institutes of Health (NIH)