scholarly journals Beyond bacterial vaginosis: vaginal lactobacilli and HIV risk

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Eric Armstrong ◽  
Rupert Kaul
Keyword(s):  
Bacterial Vaginosis ◽  
Hiv Risk ◽  
Anaerobic Bacteria ◽  
Vaginal Microbiota ◽  
Bacterial Survival ◽  
Associated Bacteria ◽  
Eastern And Southern Africa ◽  
Hiv Acquisition ◽  
Risk Of Hiv Acquisition ◽  
Species Specific

AbstractHIV incidence continues to be unacceptably high in Eastern and Southern Africa, with women disproportionately affected. An increased per-contact risk of HIV acquisition among African, Caribbean, and other Black (ACB) women has been associated with the higher prevalence of bacterial vaginosis (BV) in these communities, wherein the vaginal microbiota is predominated by diverse pro-inflammatory anaerobic bacteria. However, while the vaginal microbiota in BV-free women is typically predominated by one of several different Lactobacillus spp., the degree of HIV protection afforded by a Lactobacillus-predominant vaginal microbiota also varies considerably. Specifically, L. crispatus is associated with an immunoregulatory genital immune environment, exclusion of BV-associated bacteria, and reduced HIV risk. In contrast, less HIV protection or exclusion of BV-associated bacteria and fewer immune benefits have been associated with L. iners—which is unfortunately the most common Lactobacillus species among ACB women. These species-specific clinical differences are underpinned by substantial genomic differences between Lactobacillus species: for instance, the much smaller genome of L. iners lacks the coding sequence for D-lactic acid dehydrogenase and cannot produce the D-lactate isomer that enhances HIV trapping in mucus but encodes for epithelial cell toxins and stress resistance proteins that may enhance bacterial survival in the context of microbiota and environmental fluctuations. While more studies are needed to elucidate whether differences in HIV protection between Lactobacillus species are due to direct genital immune effects or the exclusion of proinflammatory BV-associated bacteria, the current body of work suggests that for BV treatment to succeed as an HIV prevention strategy, it may be necessary to induce a vaginal microbiota that is predominated by specific (non-iners) Lactobacillus species.

scholarly journals Hormonal contraception and HIV acquisition among women: an updated systematic review

2020 ◽  
Vol 46 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Kathryn M Curtis ◽  
Philip C Hannaford ◽  
Maria Isabel Rodriguez ◽  
Tsungai Chipato ◽  
Petrus S Steyn ◽  
...  
Keyword(s):  
Systematic Review ◽  
Observational Study ◽  
Oral Contraceptives ◽  
Hiv Risk ◽  
Contraceptive Method ◽  
Hormonal Contraception ◽  
Hormonal Contraceptive ◽  
Contraception Use ◽  
Hiv Acquisition ◽  
Risk Of Hiv Acquisition

ObjectiveTo update a 2016 systematic review on hormonal contraception use and HIV acquisition.MethodsWe searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses.ResultsIn addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk.ConclusionsHigh-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition.

scholarly journals Effect of metronidazole on vaginal microbiota associated with asymptomatic bacterial vaginosis

2021 ◽  
Vol 3 (5) ◽  
Author(s):  
Daniel Ruiz-Perez ◽  
Makella S. Coudray ◽  
Brett Colbert ◽  
Karl Krupp ◽  
Hansi Kumari ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Anaerobic Bacteria ◽  
Vaginal Microbiota ◽  
Effective Treatment Option ◽  
Content Type ◽  
Sexually Transmitted ◽  
Link Type ◽  
Increased Risk ◽  
Oral Metronidazole

Vaginal dysbiosis-induced by an overgrowth of anaerobic bacteria is referred to as bacterial vaginosis (BV). The dysbiosis is associated with an increased risk for acquisition of sexually transmitted infections. Women with symptomatic BV are treated with oral metronidazole (MET), but its effectiveness remains to be elucidated. This study used whole-genome sequencing (WGS) to determine the changes in the microbiota among women treated with MET. WGS was conducted on DNA obtained from 20 vaginal swabs collected at four time points over 12 months from five randomly selected African American (AA) women. The baseline visit included all women who were diagnosed with asymptomatic BV and were untreated. All subjects were tested subsequently once every 2 months and received a course of MET for each BV episode during the 12 months. The BV status was classified according to Nugent scores (NSs) of vaginal smears. The microbial and resistome profiles were analysed along with the sociodemographic metadata. Despite treatment, none of the five participants reverted to normal vaginal flora — two were consistently positive for BV, and the rest experienced episodic cases of BV. WGS analyses showed Gardnerella spp. as the most abundant organism. After treatment with MET, there was an observed decline of Lactobacillus and Prevotella species. One participant had a healthy vaginal microbiota based on NS at one follow-up time point. Resistance genes including tetM and lscA were detected. Though limited in subjects, this study shows specific microbiota changes with treatment, presence of many resistant genes in their microbiota, and recurrence and persistence of BV despite MET treatment. Thus, MET may not be an effective treatment option for asymptomatic BV, and whole metagenome sequence would better inform the choice of antibiotics.

scholarly journals Dynamic Perceived HIV Risk and Sexual Behaviors Among Young Women Enrolled in a PrEP Trial in Kenya: A Qualitative Study

2021 ◽  
Vol 3 ◽  
Author(s):  
Kenneth Ngure ◽  
Nicholas Thuo ◽  
Vallery Ogello ◽  
Catherine Kiptinness ◽  
Kevin Kamolloh ◽  
...  
Keyword(s):  
Risk Perception ◽  
High Risk ◽  
Hiv Prevention ◽  
Qualitative Study ◽  
Young Women ◽  
Hiv Risk ◽  
Sexual Behaviors ◽  
Hiv Acquisition ◽  
Risk Of Hiv Acquisition ◽  
Over Time

Background: In Kenya and elsewhere in sub-Saharan Africa, young women are disproportionately affected by the HIV epidemic compared to young men. The extent to which young women's self-perceptions about risk of HIV acquisition influence their sexual behaviors and use of HIV prevention methods remains unclear. We therefore conducted a qualitative study to explore these issues among young women enrolled in a pre-exposure prophylaxis (PrEP) trial.Methods: From January 2017 to January 2020, we conducted serial semi-structured in-depth interviews 50 purposively selected young women (18–24 years old) who were participating in the MPYA (Monitoring PrEP for Young Adult women) study—a randomized controlled trial in Thika and Kisumu, Kenya, assessing the impact of SMS reminders on PrEP adherence. Interviews were conducted at three time points (~1 week, 3, and 12 months after initiating PrEP). We used an inductive, content analytic approach to identify key themes related to risk perceptions, sexual behavior, and use of HIV prevention tools.Results: Around the time of enrollment, most of the 50 women interviewed reported being at high risk of HIV because of their own sexual behaviors, such as inconsistent condom use, multiple sexual partners, and transactional sex. Additionally, high risk perception was based on the behavior of their partners, such as refusing to use condoms and being unsure of their partner's HIV status. Young women's perceived risk of HIV acquisition was a key motivator for PrEP initiation and continuation. During PrEP use, participants reported feeling protected and at less risk compared to peers who were not taking PrEP. Some reported no longer using condoms because they were confident that PrEP provided enough protection. Over time, many young women reported reducing risky sexual behaviors because of the regular counseling and HIV testing they received as part of their PrEP services. This lowered risk perception was in most cases accompanied by discontinuation of PrEP.Conclusions: HIV risk perception among young women in Kenya was dynamic and influenced their use of PrEP and condoms over time, suggesting an often-deliberate approach to HIV prevention and sexual health.

scholarly journals Copper intrauterine device use and HIV acquisition in women: a systematic review

2020 ◽  
Vol 46 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Philip C Hannaford ◽  
Angeline Ti ◽  
Tsungai Chipato ◽  
Kathryn M Curtis
Keyword(s):  
Observational Study ◽  
Hiv Risk ◽  
Intrauterine Device ◽  
Cochrane Library ◽  
Hiv Incidence ◽  
Increased Risk ◽  
Significant Difference ◽  
Hiv Acquisition ◽  
Risk Of Hiv Acquisition ◽  
Copper Intrauterine Device

ObjectivesTo review systematically copper intrauterine device (Cu-IUD) use and HIV acquisition in women.MethodsWe searched Pubmed, Embase and the Cochrane Library between database inception and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using an unspecified IUD or Cu-IUD compared with non-hormonal or no contraceptive users, or hormonal contraceptive users. We extracted information from included studies, assessed study quality, and summarised study findings.ResultsFrom 2494 publications identified, seven met our inclusion criteria. One randomised controlled trial (RCT), judged “informative with few limitations”, found no statistically significant differences in HIV risk between users of the Cu-IUD and either intramuscular depot medroxyprogesterone acetate (DMPA-IM) or levonorgestrel implant. One observational study, deemed “informative but with important limitations”, found no statistically significant difference in HIV incidence among IUD users compared with women who had tubal ligation or who were not using any contraception. Another “informative but with important limitations” observational study found no difference in HIV incidence between Cu-IUD users and DMPA or norethisterone enanthate injectable, or implant users. An RCT considered “unlikely to inform the primary question” also found no difference in HIV risk between Cu-IUD and progestogen-only injectable users. Findings from the other three “unlikely to inform the primary question” cohort studies were consistent with the more robust studies suggesting no increased risk of HIV acquisition among Cu-IUD users.ConclusionThe collective evidence, including that from a large high-quality RCT, does not indicate an increased risk of HIV acquisition among users of Cu-IUDs.

Characterisation of the Vaginal Microbiota Using Culturomics and Metagenomics Suggests Transplantation of Gut Microbiota Into the Vagina During Bacterial Vaginosis

2020 ◽  
Author(s):  
Khoudia Diop ◽  
Ndeye Safietou Fall ◽  
Anthony Levasseur ◽  
Nafissatou Diagne ◽  
Dipankar Bachar ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Bacterial Vaginosis ◽  
Bacterial Diversity ◽  
Bacterial Species ◽  
Anaerobic Bacteria ◽  
Common Species ◽  
Vaginal Microbiota ◽  
Normal Flora ◽  
Potential Development ◽  
Human Vagina

Abstract Background: Bacterial vaginosis is a very common vaginal disorder, with a gynaeco-obstetrical impact, but remains poorly understood. Current antibiotic treatment most often fails. Our objective was to exhaustively map the bacterial community present in bacterial vaginosis and normal flora, using not only a molecular approach but also a highly efficient culture approach, culturomics. Vaginal bacterial diversity was evaluated using both strategies for 24 Caucasian French women, including 7 cases of bacterial vaginosis, and 10 rural Senegalese women, including 5 cases of bacterial vaginosis. An additional 16 specimens (three cases of bacterial vaginosis and 13 normal flora) obtained during the follow-up visits of five French women with bacterial vaginosis were analysed using metagenomics.Results: The combination of culturomics and metagenomics reveals the richness and diversity of vaginal microbiota. Our data demonstrated that compared to healthy women, those with bacterial vaginosis present a shift in vaginal flora. The microbiota of the bacterial vaginosis group can be easily distinguished from that of healthy group by their increased bacterial diversity, abundance of Bacteroidales and Leptotrichiaeceae, and depletion of Proteobacteria and Lactobacillaceae species. In addition, a complex of 10 genera was associated with bacterial vaginosis: Gardnerella, Atopobium, Snethia, Aerococcus, Prevotella, Gemella, Facklamia, Porphyromonas, Mycoplasma, and Urinacoccus. Overall, the microbial population detected in bacterial vaginosis flora was largely similar to the bacterial communities found in gut microbiota. The two approaches showed a diverse vaginal microbiota that was largely non-overlapping, with only 146 common species. Furthermore, culturomics extends the repertoire of human-associated bacteria with the isolation of 27 new bacterial species.Conclusions: This study provides the most representative topology of the vaginal microbiota of normal flora and bacterial vaginosis and suggests the transplantation of gut microbiota into the vagina during bacterial vaginosis. Several sets of clinically relevant anaerobic bacteria and new species were also isolated from the human vagina, confirming that some previously “uncultivated” species may be cultivated using an appropriate strategy. Exhaustive characterisation of vaginal microbiota will enable a better understanding and management of bacterial vaginosis. Obtaining isolates will allow us to explore the bacterial interactions of the vaginal microbiota and will serve as a basis for the potential development of bacteriotherapy to prevent or treat vaginal dysbiosis.

Impact of Dapivirine and Placebo Vaginal Rings on the Microbiota of Adolescent, Lactating, and Postmenopausal Females

2021 ◽  
Author(s):  
Michele N Austin ◽  
Leslie A Meyn ◽  
Hilary A Avolia ◽  
Melinda A Petrina ◽  
Lisa A Cosentino ◽  
...  
Keyword(s):  
Group B Streptococcus ◽  
Secondary Analysis ◽  
Vaginal Microbiota ◽  
Vaginal Ring ◽  
Vaginal Fluid ◽  
Adult Women ◽  
Before And After ◽  
Group B ◽  
Hiv Acquisition ◽  
Risk Of Hiv Acquisition

Abstract Background A 25 mg dapivirine vaginal ring has been demonstrated to reduce risk of HIV acquisition in nonpregnant adult women. In this secondary analysis of studies conducted in US adolescent, lactating, and postmenopausal females, vaginal microbiota was assessed prior to and after ring use, and between dapivirine and placebo ring users. Methods Vaginal fluid swabs were collected before and after product use for the evaluation of microbiota using Nugent’s criteria, quantitative culture, and qPCR. Results Vaginal ring use did not impact bacterial vaginosis prevalence among the three populations and was associated with minimal shifts in microbiota. Adolescents in both arms demonstrated an increased prevalence of Lactobacillus crispatus and a decrease in quantity of Megasphaera lornae. Postmenopausal active and placebo ring users demonstrated an increased prevalence of lactobacilli and non-albicans yeast while dapivirine ring users demonstrated an increased prevalence of Candida albicans, and increased quantity of Group B Streptococcus (GBS) and non-albicans yeasts. Prevotella species were increased in lactating women while P. timonensis increased in prevalence and concentration among adolescent and postmenopausal women and P. bivia increased in prevalence among adolescent dapivirine ring users. Conclusions Dapivirine vaginal ring use was associated with minimal changes in the vaginal microbiota that are likely not clinically significant.

scholarly journals Diversity of Vaginal Microbiota Affects Epithelial Barrier Permeability Among African Pregnant Women

2021 ◽  
Author(s):  
Lois Bayigga BBLT ◽  
Rose Nabatanzi ◽  
Emilie Mausser ◽  
David P. Kateete ◽  
Musa Sekikubo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
Bacterial Cell ◽  
Vaginal Microbiota ◽  
Epithelial Barrier ◽  
Vaginal Epithelial Cells ◽  
Hiv Acquisition ◽  
Risk Of Hiv Acquisition ◽  
Pro Inflammatory Cytokines

Abstract BackgroundWomen with diverse genital anaerobic bacterial communities, are at over 4-fold higher risk of HIV acquisition than women with a Lactobacillus-rich vaginal microbiome. The mechanisms underlying this are poorly understood. We set out to examine how vaginal microbiota diversity affects epithelial integrity in HIV sero-negative pregnant women. We also investigated how HIV infection alters mucosal integrity within the prevalent genital microbiome diversity.MethodsWe assessed epithelial permeability by measuring the concentrations of tight junction proteins, claudin-1 and zonula occludens- (ZO)-1, in cervico-vaginal lavages (CVL) by enzyme-linked immunosorbent assay (ELISA). Cytokines in the vaginal fluids were measured by multiplex magnetic bead assay to establish the inflammatory state. Bacterial cell-free supernatants were used to treat vaginal epithelial cells and tissues, mimicking the in-vivo vaginal milieu. Gene and protein expression levels of tight junctions of vaginal epithelial cells and tissues in response to treatment were quantified by QuantiGene™ Plex Gene Expression Assay and by western blot respectively. The cytokine response of vaginal epithelial cells, VK2 (E6/E7, ATCC® CRL-2616™), to bacterial cell-free supernatants was measured by ELISA method.Results Among women with CT3 cervicotype, HIV sero-negative pregnant women had significantly higher claudin-1 in their CVL than the HIV-infected pregnant women (p=0.0011). IL-8 (p=0.0028), IL-1beta (p<0.0001) and TNF-alpha (p=0.0283) were significantly higher among HIV-negative pregnant women with a non-Lactobacillus dominant vaginal microbiota than those with a Lactobacillus-dominant vaginal microbiota. Bacterial cell-free supernatants from Lactobacillus elicited low levels of pro-inflammatory cytokines IL-1alpha, IL8, IL-6 and IL-1 beta in comparison to media and G. vaginalis. Treatment with G. vaginalis supernatant lowers claudin-1 and claudin-4 expression yet presence of either L. crispatus or L. iners mitigates this effect of G. vaginalis as observed by immuno-staining of treated vaginal cells.Conclusions Pregnant women with a non-Lactobacillus dominant microbiome had a disrupted epithelial barrier and elevated pro-inflammatory cytokines, making them at a higher risk of HIV acquisition than women with a Lactobacillus-dominant microbiome. Targeting vaginal microbiota and/or its effects on the vaginal epithelium and cervico-vaginal milieu can potentially lower rates of HIV acquisition and transmission.

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