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A comprehensive approach to preventing HIV infection in infants has been recommended, including: (a) preventing HIV in young women, (b) reducing unintended pregnancies among HIV-infected women, (c) preventing vertical transmission (PMTCT), and (d) providing care, treatment, and support to HIV-infected women and their families. Most attention has been given to preventing vertical transmission based on analysis showing nevirapine to be inexpensive and cost-effective.The following were determined using data from eight African countries: national program costs and impact on infant infections; reductions in adult HIV prevalence and unintended pregnancies among HIV-infected women that would have equivalent impact on infant HIV infections averted as the nevirapine intervention; and the cost threshold for drugs with greater efficacy than nevirapine yielding an equivalent cost per DALY saved.Average national annual program cost was $4.8 million. There was, per country, an average of 1898 averted infant HIV infections (US$2517 per HIV infection and US$84 per DALY averted). Lowering HIV prevalence among women by 1.25% or reducing unintended pregnancy among HIV-infected women by 16% yielded an equivalent reduction in infant cases. An antiretroviral drug with 70% efficacy could cost US$152 and have the same cost per DALY averted as nevirapine at 47% efficacy.Cost-effectiveness of nevirapine prophylaxis is influenced by health system costs, low client uptake, and poor effectiveness of nevirapine. Small reductions in maternal HIV prevalence or unintended pregnancy by HIV-infected women have equivalent impacts on infant HIV incidence and should be part of an overall strategy to lessen numbers of infant infections.