Objectives To determine the impact of time between initiating highly active antiretroviral therapy (HAART) and delivery – duration of antenatal HAART – on perinatal HIV infection. Design We conducted a retrospective cohort analysis of pregnant HIV-infected women in Lusaka, Zambia. Women in our cohort were receiving HAART and had an infant HIV polymerase chain reaction (PCR) test between 3 and 12 weeks of life. Methods We examined factors associated with infant HIV infection and performed a locally weighted regression analysis to examine the effect of duration of antenatal HAART on perinatal HIV infection. Results From January 2007 to March 2010, 1,813 HIV-infected pregnant women met inclusion criteria. Mean gestational age at first antenatal visit was 21 weeks (standard deviation (SD)+/−6), median CD4+ cell count was 231 cells/uL (interquartile range (IQR) 164 – 329), and median duration of antenatal HAART was 13 weeks (IQR 8 – 19). 59 (3.3%) infants were HIV-infected. Duration of antenatal HAART was the most important predictor of perinatal HIV transmission. Compared to women initiating HAART at least 13 weeks prior to delivery, women on HAART for ≤ 4 weeks had a 5.2-fold increased odds of HIV transmission (95% confidence interval (CI): 2.5 –11.0). Locally weighted regression analysis suggested limited additional prophylactic benefit beyond 13 weeks on antenatal HAART. Conclusions Low rates of mother-to-child HIV transmission can be achieved within programmatic settings in Africa. Maximal effectiveness of prevention of mother-to-child transmission (PMTCT) programs is achieved by initiating HAART at least 13 weeks prior to delivery.

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