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Background: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Given that the C-type lectin receptor, dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/ lymph node-specific ICAM-grabbing non-integrin (L-SIGN)), can interact with pathogens including HIV-1 and is expressed at the maternal-fetal interface, we hypothesized that it could influence MTCT of HIV-1. Methods and Findings: To investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of 197 HIV-infected mothers and their infants recruited in Harare, Zimbabwe. Infants harbouring two copies of DC-SIGNR H1 and/or H3 haplotypes (H1-H1, H1-H3, H3-H3) had a 3.6-fold increased risk of in utero (IU) (P = 0.013) HIV-1 infection and a 5.7-fold increased risk of intrapartum (IP) (P = 0.025) HIV-1 infection after adjusting for a number of maternal factors. The implicated H1 and H3 haplotypes share two single nucleotide polymorphisms (SNPs) in promoter region (p-198A) and intron 2 (int2-180A) that were associated with increased risk of both IU (P = 0.045 and P = 0.003, respectively) and IP (P = 0.025, for int2-180A) HIV-1 infection. The promoter variant reduced transcriptional activity in vitro. In homozygous H1 infants bearing both the p-198A and int2-180A mutations, we observed a 4-fold decrease in the level of placental DC-SIGNR transcripts, disproportionately affecting the expression of membrane-bound isoforms compared to infant noncarriers (P = 0.011). Conclusion: These results suggest that DC-SIGNR plays a crucial role in MTCT of HIV-1 and that impaired placental DC-SIGNR expression increases risk of transmission. [ABSTRACT FROM AUTHOR]

International guidance on HIV and infant feeding has evolved over the last decade. In response to these changes, we designed, implemented, and evaluated an education and counseling program for new mothers in Harare, Zimbabwe. The program was implemented within the ZVITAMBO trial, in which 14,110 mother-baby pairs were enrolled within 96 h of delivery and were followed at 6 wk, 3 mo, and 3-mo intervals. Mothers were tested for HIV at delivery but were not required to learn their test results. Infant feeding patterns were determined using data provided up to 3 mo. Formative research was undertaken to guide the design of the program that included group education, individual counseling, videos, and brochures. The program was introduced over a 2-mo period: 11,362, 1311, and 1437 women were enrolled into the trial before, during, and after this period. Exclusive breast-feeding was recommended for mothers of unknown or negative HIV status, and for HIV-positive mothers who chose to breast-feed. A questionnaire assessing HIV knowledge and exposure to the program was administered to 1996 mothers enrolling after the program was initiated. HIV knowledge improved with increasing exposure to the program. Mothers who enrolled when the program was being fully implemented were 70% more likely to learn their HIV status early (<3 mo) and 8.4 times more likely to exclusively breast-feed than mothers who enrolled before the program began. Formative research aided in the design of a culturally sensitive intervention, The intervention increased relevant knowledge and improved feeding practices among women who primarily did not know their HIV status. [ABSTRACT FROM AUTHOR]