The Vaginal Microbiota over an 8- to 10-Year Period in a Cohort of HIV-Infected and HIV-Uninfected Women

Abstract

BackgroundWe identified predominant vaginal microbiota communities, changes over time, and how this varied by HIV status and other factors in a cohort of 64 women.MethodsBacterial DNA was extracted from reposited cervicovaginal lavage samples collected annually over an 8–10 year period from Chicago Women’s Interagency HIV Study participants: 22 HIV-negative, 22 HIV-positive with stable infection, 20 HIV-positive with progressive infection. The vaginal microbiota was defined by pyrosequencing of the V1/V2 region of the 16S rRNA gene. Scheduled visits included Bacterial vaginsosis (BV) screening; clinically detected cases were referred for treatment. Hierarchical clustering identified bacterial community state types (CST). Multinomial mixed effects modeling determined trends over time in CST, by HIV status and other factors.ResultsThe median follow-up time was 8.1 years (range 5.5–15.3). Six CSTs were identified. The mean relative abundance (RA) of Lactobacillus spp. by CST (with median number of bacterial taxa) was: CST-1–25.7% (10), CST-2–27.1% (11), CST-3–34.6% (9), CST-4–46.8% (9), CST-5–57.9% (4), CST-6–69.4% (2). The two CSTs representing the highest RA of Lactobacillus and lowest diversity increased with each additional year of follow-up (CST-5, adjusted odds ratio (aOR) = 1.62 [95% CI: 1.34–1.94]; CST-6, aOR = 1.57 [95 CI: 1.31–1.89]), while the two CSTs representing lowest RA of Lactobacillus and higher diversity decreased with each additional year (CST-1, aOR = 0.89 [95% CI: 0.80–1.00]; CST-2, aOR = 0.86 [95% CI: 0.75–0.99]). There was no association between HIV status and CST at baseline or over time. CSTs representing lower RA of Lactobacillus were associated with current cigarette smoking.ConclusionsThe vaginal microbial community significantly improved over time in this cohort of women with HIV and at high risk for HIV who had regular detection and treatment referral for BV.

Associations of the vaginal microbiota with HIV infection, bacterial vaginosis, and demographic factors

“…Analysis of the vaginal microbiome showed notable associations between high diversity states, high pH, and BV as inferred from Nugent scores, paralleling previous studies [9, 11, 18, 39] . Previous studies have differed on associations between HIV status and BV [26–28, 30, 31] —here we found that HIV+ status was correlated with BV status.…”

“…DNA was purified from cervical or cervicovaginal mucus, then samples amplified with 16S rRNA gene primers targeting the V1V2 region [34–37] . This primer set has been used in previous studies of the vaginal microbiome [30] , and is generally effective at recovering 16S sequences from vaginal organisms. Sequence data was acquired using the Illumina MiSeq platform (paired end sequencing, average of 50,127 sequences per sample).…”

“…BV is known to be more common in African American women, motivating studies of associations with HIV infection [29] . In contrast, a study of the vaginal microbiome in 64 women in Chicago showed no differences associated with HIV infection [30] . Another study, comparing vaginal microbiota in women from Rwanda and the US together with HIV status, found modest differences for both geographic site and infection status [31] .…”

Gardnerella vaginalis Subgroups Defined by cpn60 Sequencing and Sialidase Activity in Isolates from Canada, Belgium and Kenya

“…vaginalis may actually consist of several species with distinct roles in BV pathogenesis has only recently been investigated [5, 7, 8]. Studies based on 16S rRNA variable-region targeted sequencing have known biases against detecting Gardnerella at all [24, 25], much less resolving subgroups, although one early deep sequencing study did distinguish four G . vaginalis subgroups based on a single nucleotide difference in variable region 6 of the 16S rRNA gene [26].…”

An overview of major metagenomic studies on human microbiomes in health and disease

“…The "community type" was also called "community state types (CSTs)" in some later studies. Some studies further investigated the associations between vagina CSTs and vaginal health in groups of particular ages [62,63], with the influence of HIV treatment [64,65], in pregnancy and birth [66][67][68], and so on.…”