Lactobacillus-depleted vaginal microbiota in HIV-infected pregnant women are associated with increased local inflammation and preterm birth

Background Pregnant women with HIV infection have an elevated risk of preterm birth of unknown aetiology, which remains after successful suppression of HIV. Women at high risk for HIV have a common bacterial profile which has been associated with poor birth outcomes. We set out to explore factors associated with gestational age at delivery of HIV-infected pregnant women in a UK population. Methods Prospective study of HIV-1 infected (n=53) and uninfected (n=22) pregnant women in whom the vaginal microbiota and cervicovaginal cytokine milieu were assessed using metataxonomics and multiplexed immunoassays, respectively. The relationships between bacterial composition, inflammatory response, HIV status and gestational age at delivery were explored. Findings here was a high rate of preterm birth (PTB) among HIV infected women (12%). In the second trimester the vaginal microbiota was more diverse in HIV-1 infected than in uninfected women (Inverse Simpson Index, p=0.0004 and Species Observed, p=0.009). Pregnant women with HIV-1 infection had a lower prevalence of L. crispatus dominant vaginal microbiota group (VMB I, 15% vs 54%) than uninfected women and higher prevalence of L. iners dominant (VMB III, 36% vs 9% and VMB IIIB, 15% vs 5%) and mixed anaerobes (VMB IV, 21% vs 0%). VMB III/IIIB and IV were associated with PTB and with increased local inflammation (cervicovaginal fluid (CVF) cytokine concentrations in upper quartile). High bacterial diversity and anaerobic bacterial abundance were also associated with CVF pro-inflammatory cytokines, most notably Th1: IL-1b. Interpretation There is an association between local inflammation, vaginal dysbiosis and PTB in HIV infection. Understanding the potential of specific ART to influence this cascade will be important to improve birth outcomes in this population.