Ramla F Tanko1,2, Rubina Bunjun1, Smritee Dabee3, Shameem Z Jaumdally1, Maricianah Onono4, Gonasagrie Nair5, Thesla Palanee-Phillips6, Rushil Harryparsad1, Anna Ursula Happel1, Hoyam Gamieldien1, Yamkela Qumbelo1, Musalula Sinkala1, Caitlin W Scoville7, Kate Heller7, Jared M Baeten7,8, Steven E Bosinger9,10, Adam Burgener11,12,13, Renee Heffron7, Heather B Jaspan1,3, Jo Ann S Passmore1,14,15. 1. Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town, Cape Town, South Africa. 2. Medical Research Centre, Institute of Medical Research and Medicinal Plant Studies, Ministry of Scientific Research and Innovation, Yaoundé, Cameroon. 3. Seattle Children's Research Institute, Seattle, Washington, USA. 4. Kenya Medical Research Institute, Kisumu, Kenya. 5. Desmond Tutu HIV Foundation, Cape Town, South Africa. 6. Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa. 7. University of Washington, Seattle, Washington, USA. 8. Gilead Sciences, Foster City, California, USA. 9. Emory University, Atlanta, Georgia, USA. 10. Yerkes National Primate Research Center, Atlanta, Georgia, USA. 11. Center for Global Health and Diseases, Case Western Reserve University, Cleveland, USA. 12. Department of Obstetrics and Gynecology and Medical Microbiology, University of Manitoba, Winnipeg, Canada. 13. Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden. 14. National Research Foundation - Department of Science and Technology Centre for the AIDS Programme of Research in South Africa Centre of Excellence in HIV Prevention, Durban, South Africa. 15. National Health Laboratory Service, Cape Town, South Africa.
Abstract
BACKGROUND: The ECHO trial randomized women to intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG-implant), or copper intrauterine device (Cu-IUD). In a substudy of the ECHO trial, we tested the hypothesis that contraceptives influence genital inflammation by comparing cervicovaginal cytokine changes following contraception initiation. In addition, we compared cytokine profiles in women who acquired HIV (cases) versus those remaining HIV negative (controls). METHODS: Women (n = 251) from South Africa and Kenya were included. Twenty-seven cervicovaginal cytokines were measured by Luminex at baseline, and 1 and 6 months after contraceptive iTanko et alnitiation. In addition, cytokines were measured preseroconversion in HIV cases (n = 25) and controls (n = 100). RESULTS: At 6 months after contraceptive initiation, women using Cu-IUD had increased concentrations of 25/27 cytokines compared to their respective baseline concentrations. In contrast, women initiating DMPA-IM and LNG-implant did not experience changes in cervicovaginal cytokines. Preseroconversion concentrations of IL-1β, IL-6, and TNF-α, previously associated with HIV risk, correlated with increased HIV risk in a logistic regression analysis, although not significantly after correcting for multiple comparisons. Adjusting for contraceptive arm did not alter these results. CONCLUSIONS: Although Cu-IUD use broadly increased cervicovaginal cytokine concentrations at 6 months postinsertion, these inflammatory changes were found not to be a significant driver of HIV risk. CLINICAL TRIALS REGISTRATION: NCT02550067. Published by Oxford University Press for the Infectious Diseases Society of America 2022.
BACKGROUND: The ECHO trial randomized women to intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG-implant), or copper intrauterine device (Cu-IUD). In a substudy of the ECHO trial, we tested the hypothesis that contraceptives influence genital inflammation by comparing cervicovaginal cytokine changes following contraception initiation. In addition, we compared cytokine profiles in women who acquired HIV (cases) versus those remaining HIV negative (controls). METHODS: Women (n = 251) from South Africa and Kenya were included. Twenty-seven cervicovaginal cytokines were measured by Luminex at baseline, and 1 and 6 months after contraceptive iTanko et alnitiation. In addition, cytokines were measured preseroconversion in HIV cases (n = 25) and controls (n = 100). RESULTS: At 6 months after contraceptive initiation, women using Cu-IUD had increased concentrations of 25/27 cytokines compared to their respective baseline concentrations. In contrast, women initiating DMPA-IM and LNG-implant did not experience changes in cervicovaginal cytokines. Preseroconversion concentrations of IL-1β, IL-6, and TNF-α, previously associated with HIV risk, correlated with increased HIV risk in a logistic regression analysis, although not significantly after correcting for multiple comparisons. Adjusting for contraceptive arm did not alter these results. CONCLUSIONS: Although Cu-IUD use broadly increased cervicovaginal cytokine concentrations at 6 months postinsertion, these inflammatory changes were found not to be a significant driver of HIV risk. CLINICAL TRIALS REGISTRATION: NCT02550067. Published by Oxford University Press for the Infectious Diseases Society of America 2022.
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