Zim CHIC: A cohort study of immune changes in the female genital tract associated with initiation and use of contraceptives

Achilles, Sharon L.; Meyn, Leslie A.; Mhlanga, Felix; Matubu, Allen; Stoner, Kevin A.; Beamer, May; Chirenje, Zvavahera M.; Hillier, Sharon L.

doi:10.1111/aji.13287

Cited by 13 publications

(21 citation statements)

References 28 publications

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“…Achilles et al enrolled women that were STI/HIV negative with regular menstrual cycles seeking contraception counseling in Harare, Zimbabwe, excluding those with recent hormonal contraceptive use. 29 Use of DMPA ( N = 38) associated with decreased cervical CD4+ T cells (percent and total cell numbers at days 30 and 180 after DMPA initiation, respectively) and CD11c+ antigen‐presenting cells after 180 days, but no changes in CD4+ and CD8+ T cells expressing CCR5. In terms of soluble factors, they observed a significant increase in IL‐10 at day 30, and a significant decrease in IL‐1β, and a trending decrease in IL‐8 at days 30 and 180 after DMPA initiation.…”

Section: Dmpa Use and On The Immunology Of The Vaginal Environmentmentioning

confidence: 93%

“…All of these studies included self‐selection of contraceptive method instead of randomization to contraception arm. Achilles et al enrolled women that were STI/HIV negative with regular menstrual cycles seeking contraception counseling in Harare, Zimbabwe, excluding those with recent hormonal contraceptive use 29 . Use of DMPA ( N = 38) associated with decreased cervical CD4+ T cells (percent and total cell numbers at days 30 and 180 after DMPA initiation, respectively) and CD11c+ antigen‐presenting cells after 180 days, but no changes in CD4+ and CD8+ T cells expressing CCR5.…”

Section: Dmpa Use and On The Immunology Of The Vaginal Environmentmentioning

confidence: 99%

“…An important component of this study which adds considerable value to their findings was the measurement of serum MPA concentrations (pg/mL), which peaked at day 30. However, women in the DMPA group reported having significantly increased frequency of sexual intercourse by 180 days post‐DMPA initiation compared to copper IUD and implant users 29 which could have significantly impacted these observations.…”

Section: Dmpa Use and On The Immunology Of The Vaginal Environmentmentioning

confidence: 99%

See 2 more Smart Citations

An updated review on the effects of depot medroxyprogesterone acetate on the mucosal biology of the female genital tract

Ayele

Perner

McKinnon

et al. 2021

American J Rep Immunol

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Background Access to safe, effective, and affordable contraception is important for women’s health and essential to mitigate maternal and fetal mortality rates. The progestin‐based contraceptive depot medroxyprogesterone acetate (DMPA) is a popular contraceptive choice with a low failure rate and convenient administration schedule. Aim In this review, we compiled observational data from human cohorts that examine how DMPA influences the mucosal biology of the female genital tract (FGT) that are essential in maintaining vaginal health, including resident immune cells, pro‐inflammatory cytokines, epithelial barrier function, and the vaginal microbiome Materials and Methods This review focused on the recent published literature published in 2019 and 2020. Results Recent longitudinal studies show that DMPA use associates with an immunosuppressive phenotype, increase in CD4+CCR5+ T cells, and alterations to growth factors. In agreement with previous meta‐analyses, DMPA use is associated with minimal effects of the composition of the vaginal microbiome. Cross‐sectional studies associate a more pro‐inflammatory relationship with DMPA, but these studies are confounded by inherent weaknesses of cross‐sectional studies, including differences in study group sizes, behaviors, and other variables that may affect genital inflammation. Discussion & Conclusion These recent results indicate that the interactions between DMPA and the vaginal mucosa are complex emphasizing the need for comprehensive longitudinal studies that take into consideration the measurement of multiple biological parameters.

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Section: Dmpa Use and On The Immunology Of The Vaginal Environmentmentioning

confidence: 93%

Section: Dmpa Use and On The Immunology Of The Vaginal Environmentmentioning

confidence: 99%

Section: Dmpa Use and On The Immunology Of The Vaginal Environmentmentioning

confidence: 99%

See 1 more Smart Citation

An updated review on the effects of depot medroxyprogesterone acetate on the mucosal biology of the female genital tract

Ayele

Perner

McKinnon

et al. 2021

American J Rep Immunol

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show abstract

“…The only user-directed contraceptive used by men is the penile condom, whose barrier function directly reduces HIV risk and whose impacts on penile immunology or [104,105] the penile microbiome have not been studied to our knowledge. In contrast, several contraceptive choices employed by women have important immune effects on the female genital tract.…”

Section: Contraceptionmentioning

confidence: 99%

The Penis, the Vagina and HIV Risk: Key Differences (Aside from the Obvious)

Kaul

Liu

Park

et al. 2022

Viruses

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Globally, most Human Immunodeficiency Virus type 1 (HIV) transmission occurs through vaginal–penile sex (heterosexual transmission). The local immune environment at the site of HIV exposure is an important determinant of whether exposure during sex will lead to productive infection, and the vaginal and penile immune milieus are each critically shaped by the local microbiome. However, there are key differences in the microbial drivers of inflammation and immune quiescence at these tissue sites. In both, a high abundance of anaerobic taxa (e.g., Prevotella) is associated with an increased local density of HIV target cells and an increased risk of acquiring HIV through sex. However, the taxa that have been associated to date with increased risk in the vagina and penis are not identical. Just as importantly, the microbiota associated with comparatively less inflammation and HIV risk—i.e., the optimal microbiota—are very different at the two sites. In the vagina, Lactobacillus spp. are immunoregulatory and may protect against HIV acquisition, whereas on the penis, “skin type” flora such as Corynebacterium are associated with reduced inflammation. Compared to its vaginal counterpart, much less is known about the dynamics of the penile microbiome, the ability of clinical interventions to alter the penile microbiome, or the impact of natural/induced microbiome alterations on penile immunology and HIV risk.

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“…While global guidance has treated DMPA-IM, DMPA-SC, and NET-EN similarly, a recent review of pharmacokinetic, biologic, and epidemiologic differences in MPA-and NET-based progestin-only injectable contraceptives concluded that they are likely to act differently relative to potential HIV acquisition in women, based on most of the available biological activity and epidemiological data (12). Recent findings from the Zim-CHIC study suggest that women who initiate DMPA and NET-EN exhibit some differences in genital tract immune mediators (both soluble and cellular) (13). However, changes were limited compared to those observed among women initiating the use of a copper IUD.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Incidence of Sexually Transmitted Infection in Injectable Progestin Contraception Users in South Africa

Noguchi¹,

Marrazzo²,

Richardson³

et al. 2021

Front. Reprod. Health

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Introduction: Whether intramuscular depot medroxyprogesterone acetate (DMPA-IM) and norethisterone enanthate (NET-EN) have a differential impact on the incidence of sexually transmitted infection (STI) remains unclear. In the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial, HIV-1 acquisition was higher for DMPA-IM users vs. NET-EN users. We compared DMPA-IM and NET-EN users with regard to chlamydia, gonorrhea, trichomoniasis, syphilis, and herpes simplex virus type 2 (HSV-2) infection.Materials and Methods: Prospective data were analyzed from VOICE, a randomized trial of HIV-1 chemoprophylaxis. Participants were evaluated annually and as indicated for chlamydia, gonorrhea, trichomoniasis, and syphilis. Stored specimens were tested for HSV-2. Proportional hazards models compared the risk of STI between DMPA-IM and NET-EN users.Results: Among 2,911 injectable contraception users in South Africa, 1,800 (61.8%) used DMPA-IM and 1,111 used NET-EN (38.2%). DMPA-IM and NET-EN users did not differ in baseline chlamydia: 15.1 vs. 14.3%, p = 0.54; gonorrhea: 3.4 vs. 3.7%, p = 0.70; trichomoniasis: 5.7 vs.5.0%, p = 0.40; or syphilis: 1.5 vs. 0.7%, p = 0.08; but differed for baseline HSV-2: (51.3 vs. 38.6%, p < 0.001). Four hundred forty-eight incident chlamydia, 103 gonorrhea, 150 trichomonas, 17 syphilis, and 48 HSV-2 infections were detected over 2,742, 2,742, 2,783, 2,945, and 756 person-years (py), respectively (chlamydia 16.3/100 py; gonorrhea 3.8/100 py; trichomoniasis 5.4/100 py; syphilis 0.6/100 py; HSV-2 6.4/100 py). Comparing DMPA-IM with NET-EN users, no difference was noted in the incidence of chlamydia, gonorrhea, trichomoniasis, syphilis, or HSV-2 infections, including when adjusted for confounders [chlamydia (aHR 1.03, 95% CI 0.85–1.25), gonorrhea (aHR 0.88, 95% CI 0.60–1.31), trichomoniasis (aHR 1.07, 95% CI 0.74–1.54), syphilis (aHR 0.41, 95% CI 0.15–1.10), and HSV-2 (aHR 0.83, 95% CI 0.45–1.54, p = 0.56)].Discussion: Among South African participants enrolled in VOICE, DMPA-IM and NET-EN users differed in prevalence of HSV-2 at baseline but did not differ in the incidence of chlamydia, gonorrhea, trichomoniasis, syphilis, or HSV-2 infection. Differential HIV-1 acquisition, previously demonstrated in this cohort, does not appear to be explained by differential STI acquisition. However, the high incidence of multiple STIs reinforces the need to accelerate access to comprehensive sexual and reproductive health services.

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Zim CHIC: A cohort study of immune changes in the female genital tract associated with initiation and use of contraceptives

Cited by 13 publications

References 28 publications

An updated review on the effects of depot medroxyprogesterone acetate on the mucosal biology of the female genital tract

An updated review on the effects of depot medroxyprogesterone acetate on the mucosal biology of the female genital tract

The Penis, the Vagina and HIV Risk: Key Differences (Aside from the Obvious)

Prevalence and Incidence of Sexually Transmitted Infection in Injectable Progestin Contraception Users in South Africa

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