Vaginal microbiome-hormonal contraceptive interactions associate with the mucosal proteome and HIV acquisition

Alterations to the mucosal environment of the female genital tract, such as genital inflammation, have been associated with increased HIV acquisition in women. As the microbiome and hormonal contraceptives can affect vaginal mucosal immunity, we hypothesized these components may interact in the context of HIV susceptibility. Using previously published microbiome data from 685 women in the CAPRISA-004 trial, we compared relative risk of HIV acquisition in this cohort who were using injectable depot medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN), and combined oral contraceptives (COC). In women who were Lactobacillus-dominant, HIV acquisition was 3-fold higher in women using DMPA relative to women using NET-EN or COC (OR: 3.27; 95% CI: 1.24–11.24, P = 0.0305). This was not observed in non-Lactobacillus-dominant women (OR: 0.95, 95% CI: 0.44–2.15, P = 0.895) (interaction P = 0.0686). Higher serum MPA levels associated with increased molecular pathways of inflammation in the vaginal mucosal fluid of Lactobacillus-dominant women, but no differences were seen in non-Lactobacillus dominant women. This study provides data suggesting an interaction between the microbiome, hormonal contraceptives, and HIV susceptibility.

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Innate Antibacterial Activity in Female Genital Tract Secretions Is Associated with Increased Risk of HIV Acquisition

AIDS Research and Human Retroviruses ◽

10.1089/aid.2015.0011 ◽

2015 ◽

Vol 31 (11) ◽

pp. 1153-1159 ◽

Cited By ~ 13

Author(s):

Rebecca Pellett Madan ◽

Lindi Masson ◽

Jessica Tugetman ◽

Lise Werner ◽

Anneke Grobler ◽

...

Keyword(s):

Antibacterial Activity ◽

Genital Tract ◽

Female Genital Tract ◽

Increased Risk ◽

Hiv Acquisition ◽

Risk Of Hiv Acquisition ◽

Female Genital

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Microbiome and Cervical Cancer

Pathobiology ◽

10.1159/000511477 ◽

2020 ◽

pp. 1-11

Author(s):

Cristina Paula Castanheira ◽

Mayara Luciana Sallas ◽

Rafaella Almeida Lima Nunes ◽

Noely Paula Cristina Lorenzi ◽

Lara Termini

Keyword(s):

Cervical Cancer ◽

Genital Tract ◽

Current Knowledge ◽

Disease Onset ◽

Female Genital Tract ◽

Hpv Infection ◽

Vaginal Microbiome ◽

Associated Lesions ◽

Cervical Disease ◽

Female Genital

Persistent infection with some types of mucosal human papillomavirus (HPV) is the etiological factor for the development of cervical cancer and its precursor lesions. Besides, several cofactors are known to play a role in cervical disease onset and progression either by favoring or by preventing HPV infection and persistence. The microbiome of a healthy female genital tract is characterized by the presence of 1 or few varieties of lactobacilli. However, high-throughput studies addressing the bacterial diversity and abundance in the female genital tract have shown that several factors, including hormonal levels, hygiene habits, and sexually transmitted diseases may disrupt the natural balance, favoring the outgrowth of some groups of bacteria, which in turn may favor some pathological states. Recently, the vaginal microbiome has emerged as a new variable that could greatly influence the natural history of HPV infections and their clinical impact. In this context, changes in the vaginal microbiome have been detected in women infected with HPV and women with HPV-associated lesions and cancer. However, the role of specific bacteria groups in the development/progression or prevention/regression of HPV-associated pathologies is not well understood. In this review we summarize the current knowledge concerning changes in vaginal microbiome and cervical disease. We discuss the potential functional interplay between specific bacterial groups and HPV infection outcomes.

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Role of sex hormones and the vaginal microbiome in susceptibility and mucosal immunity to HIV-1 in the female genital tract

AIDS Research and Therapy ◽

10.1186/s12981-017-0169-4 ◽

2017 ◽

Vol 14 (1) ◽

Cited By ~ 20

Author(s):

Danielle Vitali ◽

Jocelyn M. Wessels ◽

Charu Kaushic

Keyword(s):

Sex Hormones ◽

Mucosal Immunity ◽

Genital Tract ◽

Female Genital Tract ◽

Vaginal Microbiome ◽

Hiv 1 ◽

Female Genital

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Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study

The Lancet Infectious Diseases ◽

10.1016/s1473-3099(15)00429-6 ◽

2016 ◽

Vol 16 (4) ◽

pp. 441-448 ◽

Cited By ~ 56

Author(s):

Elizabeth H Byrne ◽

Melis N Anahtar ◽

Kathleen E Cohen ◽

Amber Moodley ◽

Nikita Padavattan ◽

...

Keyword(s):

Cohort Study ◽

South African ◽

Target Cell ◽

Genital Tract ◽

Female Genital Tract ◽

African Women ◽

Cell Frequency ◽

Hiv Acquisition ◽

South African Women ◽

Female Genital

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Comparison of Female Genital Tract Cytokine and Microbiota Signatures Induced by Initiation of Intramuscular DMPA and NET-EN Hormonal Contraceptives - a Prospective Cohort Analysis

Frontiers in Immunology ◽

10.3389/fimmu.2021.760504 ◽

2021 ◽

Vol 12 ◽

Author(s):

Smritee Dabee ◽

Ramla F. Tanko ◽

Bryan P. Brown ◽

Rubina Bunjun ◽

Christina Balle ◽

...

Keyword(s):

High Risk ◽

Genital Tract ◽

Cohort Analysis ◽

Female Genital Tract ◽

Vaginal Microbiota ◽

African Women ◽

Hormonal Contraceptives ◽

Rrna Gene ◽

Female Genital

BackgroundCervicovaginal inflammation, bacterial microbiota and hormonal contraceptives all influence sexual and reproductive health. To date, the effects of intramuscular depo-medroxyprogesterone acetate (DMPA-IM) versus injectable norethisterone enanthate (NET-EN) on vaginal microbiota or cytokines have not been compared back-to-back, although in-vitro data suggest that DMPA-IM and NET-EN have different pharmacokinetic and biologic activities. This study aimed at comparing the effects of DMPA-IM versus NET-EN initiation on cervicovaginal cytokines and microbiota in women at high risk for sexually transmitted infections (STIs) assigned to the respective contraceptives.MethodsWe collected socio-demographic characteristics and vaginal samples from women initiating DMPA-IM (ECHO Trial; n = 53) and NET-EN (UChoose Trial; n = 44) at baseline and after two consecutive injections to assess cytokine concentrations by Luminex, vaginal microbiota by 16S rRNA gene sequencing, STIs, bacterial vaginosis (BV) and candidiasis.ResultsCytokine concentrations did not change significantly after initiating DMPA-IM or NET-EN, although NET-EN versus DMPA-IM-associated profiles were distinct. While the abundance of bacterial taxa associated with optimal and non-optimal microbiota fluctuated with DMPA-IM use, overall community composition did not significantly change with either contraceptive. HSV-2 serology, chlamydial infection, gonorrhoea and candidiasis did not influence the associations between contraceptive type and cervicovaginal cytokines or microbiota.ConclusionsBoth DMPA-IM and NET-EN use did not lead to broad inflammatory or microbiota changes in the female genital tract of sub-Saharan African women. This suggests that NET-EN is likely a viable option for contraception in African women at high risk of BV and STIs.

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War and peace between WAP and HIV: role of SLPI, trappin-2, elafin and ps20 in susceptibility to HIV infection

Biochemical Society Transactions ◽

10.1042/bst0391427 ◽

2011 ◽

Vol 39 (5) ◽

pp. 1427-1432 ◽

Cited By ~ 26

Author(s):

Anna G. Drannik ◽

Bethany M. Henrick ◽

Kenneth L. Rosenthal

Keyword(s):

Hiv Infection ◽

Female Genital Tract ◽

War And Peace ◽

Altered Expression ◽

Hiv Susceptibility ◽

Correlates Of Protection ◽

Hiv Acquisition ◽

Innate Defence ◽

Female Genital

Despite tremendous advances in our understanding of HIV/AIDS since the first cases were reported 30 years ago, we are still a long way from understanding critical steps of HIV acquisition, pathogenesis and correlates of protection. Our new understanding of the importance of the mucosa as a target for HIV infection, as well as our recent observations showing that altered expression and responses of innate pattern recognition receptors are significantly associated with pathogenesis and resistance to HIV infection, indicate that correlates of immunity to HIV are more likely to be associated with mucosal and innate responses. Most of the heterosexual encounters do not result in productive HIV infection, suggesting that the female genital tract is protected against HIV by innate defence molecules, such as antiproteases, secreted mucosally. The present review highlights the role and significance of the serine protease inhibitors SLPI (secretory leucocyte protease inhibitor), trappin-2, elafin and ps20 (prostate stromal protein 20 kDa) in HIV susceptibility and infection. Interestingly, in contrast with SLPI, trappin-2 and elafin, ps20 has been shown to enhance HIV infectivity. Thus understanding the balance and interaction of these factors in mucosal fluids may significantly influence HIV infection.

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