Cisgender women who used the hormonal birth control shot depot medroxyprogesterone acetate (DMPA, Depo Provera) had a significantly lower risk of gonorrhea and chlamydia infections compared to women who used a hormonal implant or a copper intrauterine device (IUD) for contraception, according to a follow-up analysis of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial presented at IAS 2019, the 10th International AIDS Society (IAS) Conference on HIV Science.
Specifically, DMPA was associated with a 30% lower risk of gonorrhea infection compared to the IUD, and a 20% lower risk of chlamydia infection compared to the implant.
"I can't wrap my head around [this result]," said Carl Dieffenbach, Ph.D., director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID). "What does that mean? Does that mean DMPA is a little bit protective? ... Are the hormones causing some immune change? We just don't know."
These findings are significant because, until now, there had been no randomized clinical trials to capture the relationship between sexually transmitted infection (STI) risk and contraception, explained Jennifer Deese, Ph.D., M.P.H., with FHI 360, who presented the data at IAS 2019. Deese and her coauthors also found that STI prevalence was significantly higher among young women 16 to 24 years old compared to women 25 to 35. Although women were tested and offered treatment at baseline visits, STI incidence remained high at the end of the study.
The authors used two different analytical methods (intention to treat and behavioral analysis unit) to gauge the link between DMPA and STI incidence and found their results didn't change, The authors concluded that DMPA users "may have a lower risk of [gonorrhea] compared to copper IUD users and of [chlamydia] compared to LNG implant users."
This follow-up analysis is particularly striking when compared against the topline results from the ECHO trial, which found a slightly elevated rate of HIV infection among women using DMPA. That finding was not statistically significant, with researchers ultimately concluding there was no meaningful difference in the rate of HIV infection between the three contraceptive methods.
These results, which were published in The Lancet last month, offered new evidence that it's safe for women to continue using DMPA, which is widely used in Africa. For decades, the contraceptive method had been subject to suspicion that it might increase a woman's likelihood of contracting HIV, because of the results from several observational studies.
But ECHO was also a sobering reminder of the high rate of HIV infection among young women in the four African countries that were included in the study -- eSwatini, Kenya, South Africa, and Zambia.
A follow-up analysis presented at IAS expanded on the HIV infection rate in South Africa specifically, where a "major proportion" of all HIV transmission in the trial took place, according to Thesla Palanee-Phillips, Mmed Sci, Ph.D., with Wits Reproductive Health and HIV Institute in South Africa.
The 345 people newly diagnosed with HIV reported from South African sites translates to an incidence rate of 4.5% per 100 woman-years of follow-up. At one site, the incidence rate reached 6.8 per 100 woman-years.
At the end of the trial, the factors that predicted risk included whether a woman had an STI at study baseline and her age, with younger women at far greater risk.
"The take-home message," said Palanee-Phillips, is that "women are still at extremely high risk for HIV infection. We need more integration of PrEP delivery."
PrEP was also the subject of yet another follow-up analysis of the ECHO study presented at IAS 2019. That analysis, according to study presenter Ivana Beesham, DOH, MB BCh, with the University of Witwatersrand, South Africa, supports the integration of PrEP into HIV prevention trials.
As PrEP guidance was updated throughout the course of the ECHO trial, study coordinators adapted the study to offer PrEP to the women enrolled. About half of the study participants (3,626 women) were still enrolled in the trial when PrEP became available in their countries. Of those women, 17% (622) opted for PrEP, Beesham's analysis found.
"In ECHO, HIV incidence was high," said Beesham. "We must provide state-of-the-art HIV prevention, integrated with quality contraception. Women should be able to choose which HIV prevention options they want to use."