Genital tract VL will usually mirror the plasma VL [19], but there is increasing evidence of compartmentalization of HIV-1 between the plasma and genital tract. Genital tract HIV-1 has been detected in women with an undetectable plasma VL [20],[21] and genetic diversity of virus from the two compartments has been reported [22]. A number of factors may be responsible for this, including differential drug penetration into body compartments and the presence of genital tract infections. With increasing numbers of women in the UK aiming for and achieving a vaginal delivery an increasing number of fetuses are exposed to the cervicovaginal secretions of HIV-positive women. The clinical

significance of this is not clear. Data from the UK and Ireland [4] and France [23] showing no difference in MTCT associated with mode of delivery in women with an undetectable VL provide some reassurance that potential discordance may find more not be clinically relevant but further research is warranted. It has long been recognized that genital infections, in particular ulcerative diseases, are associated with an increased risk of sexual transmission of HIV [24],[25]. This may be a consequence of an increase in local HIV replication resulting in a higher VL in genital secretions, secondary to the presence of specific microorganisms, and/or ulceration and inflammation [26],[27].

Organisms associated with bacterial vaginosis (BV) have been shown to stimulate HIV expression Wnt inhibitor in vitro [28],[29]. A study from Kenya demonstrated a reduction in cervical mucosal shedding of HIV-1 RNA following treatment of both gonococcal and chlamydial cervicitis [30]. A study from Zimbabwe has shown a correlation between herpes simplex virus type 2 (HSV-2) antibody status and HIV-1 MTCT [31].

A study from Thailand of perinatal cervicovaginal lavages showed that HSV-2 shedding was associated with increased risk of intrapartum HIV transmission and that the effect was independent of perinatal cervicovaginal lavage and plasma HIV VL. However, this study was carried out in the context of either zidovudine monotherapy from 36 weeks or placebo [32]. That there may still be an increased risk associated with HSV shedding with patients on HAART is suggested by a randomized, double-blind, placebo-controlled trial of herpes-suppressive very therapy in HIV-1/HSV-2-infected women taking HAART in Burkina Faso, which demonstrated that valaciclovir 500 mg twice a day further reduced genital HIV replication in those women with residual HIV shedding despite HAART [33]. A study from the USA reported greater rates of HSV-2 shedding at delivery in HSV-2 seropositive women with HIV compared with HIV-negative women, 30.8% vs. 9.5% (RR 3.2, 95% CI 1.6–6.5) [34]. Future studies are needed to evaluate whether valaciclovir can reduce the risk of HIV MTCT during late pregnancy, the intrapartum period and breastfeeding.