In Lusaka, Zambia, where malaria prevalence is low, national guidelines continue to recommend that all pregnant women receive sulfadoxine–pyrimethamine (SP) for malaria prophylaxis monthly at every scheduled antenatal care visit after 16 weeks of gestation. Human immunodeficiency virus (HIV)–positive women should receive co-trimoxazole prophylaxis for HIV and not SP, but many still receive SP. We sought to determine whether increased dosage of SP is still associated with a reduced risk of low birth weight (LBW) in an area where malaria transmission is low. Our secondary objective was to determine whether any association between SP and LBW is modified by receipt of antiretroviral therapy (ART). We analyzed data routinely collected from a cohort of HIV-positive pregnant women with singleton births in Lusaka, Zambia, between February 2006 and December 2012. We used a log-Poisson model to estimate the risk of LBW by dosage of SP and to determine whether the association between SP and LBW varied by receipt of ART. Risk of LBW declined as the number of doses increased and appeared lowest among women who received three doses (adjusted risk ratio [ARR] = 0.78; 95% confidence interval [CI] = 0.64–0.95). In addition, women receiving combination ART had a higher risk of delivering an LBW infant compared with women receiving no treatment or prophylaxis (ARR = 1.18; 95% CI = 1.09–1.28), but this risk was attenuated among women who were receiving SP (risk ratio = 1.09; 95% CI = 0.99–1.21). SP was associated with a reduced risk of LBW in HIV-positive women, including those receiving ART, in a low malaria prevalence region
