BACKGROUND:

Genital ulcer disease including that caused by Herpes simplex virus type 2 (HSV-2) and syphilis facilitates sexual transmission of HIV-1. The effect of these infections on intra-partum mother-to-child-transmission (MTCT) of HIV-1 is unknown.

METHODS:

A case-control study was conducted using archived sera from HIV-1 positive women enrolled in ZVITAMBO, an MTCT trial. Cases were 509 women who transmitted HIV-1 to their infants intra-partum; controls were 1018 women whose infants remained uninfected at 12 months. Maternal serum collected at delivery, were tested for HSV-2 antibody. The 6-week post-partum sample was also tested for syphilis by RPR and TPHA to identify women with incubating or active syphilis at delivery. Rates of prevalent and incident HSV-2 and recently acquired syphilis were compared between cases and controls.

FINDINGS:

Overall prevalence of maternal HSV-2 and active syphilis at delivery were 82.5% [95% confidence interval (CI), 80.6-84.5] and 4.0% (95% CI, 3.0-5.1), respectively. Prevalent HSV-2 was associated with increased intra-partum MTCT [adjusted odds ratio (OR), 1.50; 95% CI, 1.09-2.08]. The proportion of intra-partum transmissions potentially attributable to prevalent HSV-2 infection was 28.4% (95% CI, 7.3-44.7). Maternal infection with active syphilis at delivery was not associated with intra-partum MTCT (unadjusted OR, 0.89; 95%CI, 0.49-1.59; adjusted OR, 0.64; 95% CI, 0.34-1.20).

INTERPRETATION:

HSV-2 infection is common among HIV-1-positive women and is associated with an increased risk of intra-partum MTCT. More than 25% of intra-partum MTCT may be attributable to maternal HSV-2 co-infection. Active maternal syphilis at the time of delivery is not associated with intra-partum MTCT risk.