In the midst of an “out of control” epidemic of sexually transmitted infections (STIs) in the United States, a newly recommended tool for preventing these infections has emerged. Sadly, this novel prevention strategy is not yet available to everyone who might benefit from it due to the insufficiently participatory and inclusive nature of the research used to study it.
In June 2024, the federal Centers for Disease Control and Prevention released eagerly awaited clinical guidelines for a strategy that significantly reduces the risk of sexually transmitted infections. These guidelines advise health care providers to counsel cisgender men (cisgender is when one’s current gender identity is the same as their assigned sex at birth) and transgender women who have sex with men about using doxycycline post-exposure prophylaxis (doxy PEP) if they have had a bacterial STI in the past year.
Doxy PEP involves taking a dose of doxycycline, an oral antibiotic, within 72 hours after a potentially high-risk sexual exposure. The goal is to decrease the risk of bacterial STIs: chlamydia, syphilis, and gonorrhea.
Following shared decision-making, in which providers and patients work together to make a clinical care decision, providers can prescribe doxy PEP — but at least for now, only to cisgender men and transgender women who have sex with men, groups for which doxy PEP has been shown to be highly effective.
Doxy PEP also has the potential to substantially benefit cisgender women, transgender men, and other people assigned female at birth, but these groups must wait to see if doxy PEP will be officially available to them. And health care providers are once again forced to tell cisgender women that they must wait for more studies and to tell transgender men and other people assigned female at birth that there is no doxy PEP data in these groups because they were not included in initial doxy PEP studies.
The limited reach of a novel STI prevention tool such as doxy PEP is a missed opportunity because cisgender women in the U.S. and globally have the highest rates of chlamydia. Along with other people assigned female at birth, they bear the burden of long-term health problems related to chlamydia and gonorrhea, such as pelvic inflammatory disease, ectopic pregnancy, and infertility. Rates of syphilis among cisgender women and congenital syphilis in their babies have reached record highs over the past decade. Notably, STIs can also facilitate the transmission and acquisition of HIV.
In the U.S., the epidemic of sexually transmitted infections has been marked by stark racial inequities in rates and access to screening, testing, and treatment, with Black, Latinx, and Indigenous communities being disproportionately affected.
The persistent void in generalizable knowledge about strategies for preventing STIs and HIV for cisgender women, transgender men, and other people assigned female at birth highlights the critical and urgent need for participatory and inclusive research design in clinical trials.
The need for participatory research
Participatory research involves the meaningful collaboration of community members, especially those from the population of focus, in all phases of the research, including designing the clinical trial. This helps to ensure, in part, that recruitment of participants as well as planned measures to help keep participants in the study and using the intervention are responsive to the social and structural context in which the clinical trial is taking place.
To be fair, researchers did conduct a clinical trial of doxy PEP in cisgender women, but its outcomes were affected by the same issue that plagued early clinical trials of HIV pre-exposure prophylaxis (PrEP) among cisgender women. Doxy PEP was not effective at preventing bacterial STIs among cisgender women likely because many of those randomized to receive the treatment did not use it.
This echoes findings from early HIV PrEP trials among cisgender women in sub-Saharan Africa, where oral PrEP did not appear to be effective in preventing HIV because most women in the trial did not take the medication as prescribed. A follow-up qualitative study found that participants had concerns about the investigational nature of the treatment and potential side effects, and were discouraged from taking PrEP by peers, partners, and community members. Some participants also enrolled in the study to access quality health care which would not have been available them otherwise.
Using a participatory approach to designing STI and HIV biomedical prevention clinical trials in the U.S. as well as globally could help to ensure greater buy-in among potential participants and community members for the intervention being studied as well as for the overall clinical trial.
In the case of the doxy PEP clinical trial among cisgender women, an example of a more participatory approach would be working in close collaboration with community members to plan and conduct in-depth interviews and focus groups, or even listening sessions, with community members, particularly from the population of focus, during the trial’s design phase. This could have helped to identify the reasons that might compel women to take (or not take) the antibiotic.
Although the researchers had likely hoped to mitigate any adherence-related issues by enrolling women already using oral HIV PrEP, a comprehensive understanding of their motivations for taking doxy PEP, how these motivations may differ from those for taking oral PrEP, as well as existing social support from peers, partners, and the community for doxy PEP would have been advantageous.
When research questions originate from outside the community, where priorities may be different, formative research in collaboration with community input is essential so community priorities are considered and centered in the clinical trial design.
Ensuring inclusivity in STI prevention clinical trials
While strides have been made to at least include cisgender women in these types of clinical trials, transgender men, transmasculine, non-binary, and other people assigned female at birth have been largely left out, despite studies demonstrating a critical need for interventions among these groups.
For example, one U.S.-based study found that, compared with cisgender men, transgender men who have sex with men are less likely to have been tested for HIV or STIs. Another study found that the prevalence of HIV among transmasculine individuals who have sex with men is higher than in the general population.
The lack of inclusion of transgender men and other people assigned female at birth in clinical trials limits the options available to these groups to protect themselves from HIV and STIs, and further compounds an already existing scarcity of gender-affirming care for them. An inclusive approach means designing clinical trials to ensure that all groups who could benefit from an intervention are included, particularly those that have been historically excluded.
Moving forward: inclusive and participatory research for effective prevention
Researchers can help to broaden access to available STI and HIV prevention options for marginalized communities as we work towards ending the STI and HIV epidemics by leveraging a participatory and inclusive approach to biomedical prevention clinical trials. Meaningful and in-depth collaboration with the community in developing and implementing clinical trials, especially in the planning phases, is key to accurately determining an intervention’s efficacy.
Future clinical trials must be intentional in their inclusion of transgender men and other people assigned female at birth. It is encouraging to see this is beginning to happen. A recent clinical trial of twice-yearly injectable lenacapavir for HIV PrEP in cisgender women was stopped early after showing it was 100% effective. An ongoing trial of this same approach includes transgender men and gender non-binary individuals who have sex with partners assigned male at birth.
It is no longer tenable to simply tell our patients that we don’t have the data. Wider use of participatory and inclusive research would mean we don’t have to.
Oni J. Blackstock, M.D., M.H.S., is a primary care and HIV physician and researcher, and founder and executive director of Health Justice, a racial and health equity consulting firm. Whitney C. Irie, Ph.D., M.S.W., is a social scientist and assistant professor at Boston College’s School of Social Work, a lecturer on population medicine in the Department of Population Medicine at Harvard Medical School, and an adjunct faculty member at The Fenway Institute.