Genital inflammatory status and the innate immune response to contraceptive initiation.

Nina Radzey, Rushil Harryparsad, Bahiah Meyer, Pai Lien Chen, Xiaoming Gao, Charles Morrison, Ongeziwe Taku, Anna-Lise Williamson, Celia Mehou-Loko, Florence Lefebvre d'Hellencourt, Gregory Buck, Jennifer Smit, Jerome Strauss, Kavita Nanda, Khatija Ahmed, Mags Beksinska, Myrna Serrano, Veronique Bailey, Lindi Masson, Jennifer Deese

Journal: American journal of reproductive immunology (New York, N.Y. : 1989) 2022;88(2):e13542

PMID: 35394678

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Abstract

PROBLEM

Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre-existing conditions that influence immune mediator changes in response to contraceptive initiation.

METHODS

This study included 161 South African women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD), or levonorgestrel (LNG) implant in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. We measured thirteen cytokines and antimicrobial peptides previously associated with HIV acquisition in vaginal swabs using Luminex and ELISA, before, and at 1 and 3 months after contraceptive initiation. Women were grouped according to an overall baseline inflammatory profile. We evaluated modification of the relationships between contraceptives and immune mediators by baseline inflammation, demographic, and clinical factors.

RESULTS

Overall, LNG implant and copper IUD initiation were associated with increases in inflammatory cytokines, while no changes were observed following DMPA-IM initiation. However, when stratifying by baseline inflammatory profile, women with low baseline inflammation in all groups experienced significant increases in inflammatory cytokines, while those with a high baseline inflammatory profile experienced no change or decreases in inflammatory cytokines.

CONCLUSION

We conclude that pre-contraceptive initiation immune profile modifies the effect of contraceptives on the FGT innate immune response.

Address: Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa.; FHI 360, Durham, North Carolina, USA.; Virginia Commonwealth University, Richmond, Virginia, USA.; MatCH Research Unit (MRU), Department of Obstetrics and Gynaecology, University of the Witwatersrand, Durban, South Africa.; Setshaba Research Centre, Tshwane, South Africa.; Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa.; Setshaba Research Centre, Tshwane, South Africa.; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa.; Disease Elimination Program, Life Sciences Discipline, Burnet Institute, Melbourne, Australia.; Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.; Central Clinical School, Monash University, Melbourne, Australia.; RTI International, Research Triangle Park, North Carolina, USA.

DOI: 10.1111/aji.13542

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MeSH Terms: Contraceptive Agents, Female, Cytokines, Female, Genitalia, HIV Infections, Humans, Immunity, Innate, Inflammation, Intrauterine Devices, Copper, Levonorgestrel, Medroxyprogesterone Acetate