The Effect of Intermittent Preventive Treatment during Pregnancy on Malarial Antibodies Depends on HIV Status and Is Not Associated with Poor Delivery Outcomes

Abstract

Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in sub-Saharan Africa. However, studies reporting the effect of IPTp on malaria-specific immunity are scarce and are based on findings in human immunodeficiency virus (HIV)-negative primigravidae. Plasma samples obtained from 302 pregnant women (177 who were HIV negative, 88 who were HIV positive, and 37 who were of unknown HIV status) participating in a placebo-controlled trial of IPTp with SP (IPTp-SP) were analyzed for the presence of antibodies against merozoite antigens, whole asexual parasites, and variant surface antigens from chondroitin sulfate A-binding and nonbinding lines. Antibody levels were compared between intervention groups, and their association with morbidity outcomes was assessed. HIV-positive mothers receiving SP had lower levels of peripheral antibodies against apical membrane antigen-1 and variant surface antigens, as well as lower levels of cord antibodies against erythrocyte-binding antigen-175 and parasite lysate, than did HIV-positive placebo recipients. No difference between intervention groups was observed among HIV-negative mothers. High antibody levels were associated with maternal infection and an increased risk of a first malaria episode in infants. Antibody responses were not consistently associated with reduced maternal anemia, prematurity, or low birth weight. The IPTp-associated reduction in antibodies in HIV-infected women, but not in HIV-uninfected women, may reflect a higher efficacy of the intervention in preventing malaria among HIV-positive mothers. This reduction did not translate into an enhanced risk of malaria-associated morbidity in mothers and infants. Trial registration. Clinicaltrials.gov identifier NCT00209781.