Highly diverse anaerobe-predominant vaginal microbiota among HIV-infected pregnant women in Zambia

Abstract

Vaginal dysbiosis has been shown to increase the risk of some adverse birth outcomes. HIV infection may be associated with shifts in the vaginal microbiome. We characterized microbial communities in vaginal swabs collected between 16–20 gestational weeks in the Zambian Preterm Birth Prevention Study to investigate whether HIV and its treatment alter the microbiome in pregnancy. We quantified relative abundance and diversity of bacterial taxa by whole-genome shotgun sequencing and identified community state types (CST) by hierarchical clustering. Associations between exposures—HIV serostatus (HIV+ vs HIV-) and preconceptional ART (ART+ vs ART-)—and microbiome characteristics were tested with rank-sum, and by linear and logistic regression, accounting for sampling by inverse-probability weighting. Of 261 vaginal swabs, 256 (98%) had evaluable sequences; 98 (38%) were from HIV+ participants, 55 (56%) of whom had preconceptional ART exposure. Major CSTs were dominated by: L. crispatus (CST 1; 17%), L.] iners (CST 3; 32%), Gardnerella vaginalis (CST 4-I; 37%), G. vaginalis & Atopobium vaginae (CST 4-II; 5%), and other mixed anaerobes (CST 4-III; 9%). G. vaginalis was present in 95%; mean relative abundance was higher in HIV+ (0.46±0.29) compared to HIV- participants (0.35±0.33; rank-sum p = .01). Shannon diversity was higher in HIV+/ART+ (coeff 0.17; 95%CI (0.01,0.33), p = .04) and HIV+/ART- (coeff 0.37; 95%CI (0.19,0.55), p < .001) participants compared to HIV-. Anaerobe-dominant CSTs were more prevalent in HIV+/ART+ (63%, AOR 3.11; 95%CI: 1.48,6.55, p = .003) and HIV+/ART- (85%, AOR 7.59; 95%CI (2.80,20.6), p < .001) compared to HIV- (45%). Restricting the comparison to 111 women in either CST 3 (L. iners dominance) or CST 1 (L. crispatus dominance), CST 3 frequency was similar in HIV- (63%) and HIV+/ART- participants (67%, AOR 1.31; 95%CI: (0.25,6.90), p = .7), but higher in HIV+/ART+ (89%, AOR 6.44; 95%CI: (1.12,37.0), p = .04). Pregnant women in Zambia, particularly those with HIV, had diverse anaerobe-dominant vaginal microbiota.

The Role of the Cervicovaginal Microbiome on the Genesis and as a Biomarker of Premalignant Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer

“…Similarly, a report from HIV+ pregnant women in Zambia showed that they had higher microbiome diversity, greater abundance of G. vaginalis and A. vaginae and lack of L. crispatus when compared to HIV-pregnant participants. Also, L. iners enrichment was observed in HIV-individuals and in HIV+ subjects with preconceptional ART exposure [109]. These findings corroborate the association of specific bacteria with cervical premalignant lesions.…”

Lactobacillus-Depleted Vaginal Microbiota in Pregnant Women Living With HIV-1 Infection Are Associated With Increased Local Inflammation and Preterm Birth

“…These communities were typically enriched for G. vaginalis and deplete in Lactobacillus species, particularly L. crispatus , which has been reported to provide protection against adverse pregnancy outcomes including PTB in a number of patient cohorts ( Kindinger et al., 2017 ; Brown et al., 2018 ; Fettweis et al., 2019 ). In addition to our study of European-based PWLWH, increased vaginal bacterial diversity has been recently observed in PWLWH in Zimbabwe and Zambia ( Price et al., 2019 ; Gudza-Mugabe et al., 2020 ), suggesting it is characteristic of HIV infection in both non-pregnant and pregnant women.…”

The Association Between Vaginal Microbiota Dysbiosis, Bacterial Vaginosis, and Aerobic Vaginitis, and Adverse Pregnancy Outcomes of Women Living in Sub-Saharan Africa: A Systematic Review

“…Most studies had an observational design, and their analysis should be interpreted with caution since causality and confounding are two factors that can lead to the overestimation of an association (OR), and the latter were not always adjusted for. The decision to include intervention and cross-sectional studies and studies that did not adjust for potential confounders was due to the limited number of original studies available on the VMB, AV, and BV in pregnant women in the sub-Saharan region (134)(135)(136). Another factor contributing to the heterogeneity of included studies is the different measurements used for the same outcome and the annotation of the GA or trimester at sampling collection.…”