DoxyPEP Implementation Preferences for Bacterial STD Prevention Among Gay, Bisexual, and Other Men Who Have Sex with Men Living With and Without HIV in Los Angeles: A Mixed-Methods Approach

Abstract

Bacterial sexually transmitted diseases (STDs) remain prominent in the United States among gay, bisexual, and other men who have sex with men (GBMSM). Doxycycline for post-exposure prophylaxis (DoxyPEP) is a regimen by which the antibiotic doxycycline is taken after sex to prevent bacterial STDs, such as, chlamydia, gonorrhea, and syphilis. Despite this, this study was conducted because there are a limited number of publications that describe GBMSM’s knowledge of, and interest in, taking DoxyPEP and preferences regarding its implementation. We conducted a mixed-methods study between November 2023 and March 2024. Participants (N = 21) completed a semi-structured interview and survey and were eligible if they were a cisgender man who reported having anal sex with another man in the past year and lived in the greater Los Angeles area. Interviews were recorded and transcribed and were analyzed using thematic content analysis. The majority of participants identified as gay (90%) and a racial/ethnic minority (86%); 33% were living with HIV and 43% had been diagnosed with an STD in the prior year. Participants’ mean age was 40 years (standard deviation [SD] = 15) and they reported an average of 4.5 (SD = 2.27) sexual partners in the past year. Interviews revealed that knowledge of DoxyPEP was low (28%), but most (81%) were interested in using DoxyPEP after learning about its potential. The vast majority were willing to pay $10–$20 for a 1-month supply but preferred that it be free or covered by insurance. Most preferred to get DoxyPEP from a medical provider or over-the-counter at a pharmacy. Others suggested sexualized venues, such as private sex parties, bathhouses, sex clubs, etc. The greatest concerns about its use included possible side effects, antibiotic resistance, or that it would lead to decreased condom use and increased number of sex partners. A common misconception was that DoxyPEP could prevent both a bacterial STD and HIV. DoxyPEP has strong potential as a widely accepted STD prevention method, but its successful adoption will require proactive strategies to increase GBMSM’s knowledge. Implementation programs might consider nontraditional venues where sex between men is regularly occurring.

Introduction

Sexually transmitted diseases (STDs) remain a prominent public health issue in the United States, disproportionately impacting gay, bisexual, and other men who have sex with men (GBMSM), adolescents and young adults, people living with HIV, and Black and African American individuals. ^1,2 Many bacterial STDs, including chlamydia, gonorrhea, and syphilis, can be asymptomatic. If untreated, these STDs can lead to physical health complications, including but not limited to urethritis, epididymitis, proctitis, chronic pain, and neurological and cardiovascular complications. ³ Mental health and socioeconomic impacts from untreated STDs can be equally disruptive as physical consequences of STDs, including experiencing stigma or discrimination, anxiety, depression, relationship strain, increased health care costs, and decreased work and productivity. ⁴ The presence of a bacterial STD increases the risk for both HIV acquisition and transmission through direct mucosal disturbance, recruitment of HIV target cells to the genital tract, and by elevated HIV viral load in plasma and genital secretions. ^{5 –7} Despite the potential negative health outcomes from having an STD, STD screening is underutilized by GBMSM. ^8,9

Doxycycline is a well-tolerated broad-spectrum antimicrobial with the majority of adverse effects (namely, gastrointestinal symptoms and photosensitivity) resolving upon its discontinuation. ^10,11 Currently, doxycycline is a first-line treatment for chlamydia and second-line treatment for syphilis; its usage as a treatment for gonorrhea is limited due to increasing antimicrobial resistance in various Neisseria gonorrheae strains. ^3,10,12

In addition to its uses for STD treatment, clinical trials were initiated to investigate the efficacy of taking doxycycline after a potential bacterial STD exposure for post-exposure prophylaxis (DoxyPEP). The first such study included 30 MSM living with HIV with a history of two or more syphilis infections, randomized to either daily doxycycline or contingency management. At a follow-up of 48 weeks, those participants randomized to the daily doxycycline condition demonstrated an overall reduction (odds ratio 0.27) in gonorrhea, chlamydia, and syphilis infections compared with the contingency management group. ¹³ A randomized trial of adult GBMSM taking antiviral pre-exposure prophylaxis (PrEP) for the prevention of HIV infection found that doxycycline taken within a day after sex decreased risk of syphilis and chlamydia, with no change in risk of gonorrhea. ¹⁴ A subsequent, larger trial (n = 501) of MSM and transgender women (TGW) either with HIV or using PrEP for HIV prevention diagnosed with chlamydia, syphilis, or gonorrhea in the past year randomized participants to either 200 mg of DoxyPEP within 72 h of condomless sex or standard of care. Across 12 months with quarterly follow-ups, the collective occurrence of chlamydia, syphilis, and gonorrhea among participants randomized to DoxyPEP was two-thirds lower than those randomized to standard of care. ¹⁵ As a result of these trials, as of 2024, the Centers for Disease Control and Prevention (CDC) Clinical Guidelines now recommend 200 mg of doxycycline be taken as soon as possible within 72 h after potential STD exposure (i.e., after anal, oral, or vaginal sex) for cisgender GBMSM and TGW who have been diagnosed with a bacterial STD in the past year. ¹⁰

Quantitative online surveys have been implemented to assess interest and acceptability of DoxyPEP/PrEP to prevent STDs and found that the majority of GBMSM, TGW, and nonbinary people surveyed would be interested in using it. ^{16 –19} One of these studies additionally found 89.5% of health care providers in Southern California were favorable of prescribing DoxyPEP for STD prevention if recommended by the CDC, with a noted concern of antimicrobial resistance. ¹⁷ Those survey questions were not open-ended, limiting possible areas of interest and concern that could be expressed by participants.

Qualitative research could be beneficial in addressing this gap, but qualitative studies in this area are limited. Qualitative studies, including substudies among DoxyPEP clinical trial participants, have largely supported quantitative findings, with participants indicating overall interest and acceptability with concerns about side effects, antibiotic resistance, and potential stigma. ^{20 –23} However, of the qualitative studies published, interviews were conducted before CDC guidance on DoxyPEP use was released and few included men living with HIV. ^{20 –22} Further, preferences for accessing DoxyPEP (i.e., cost and setting) among GBMSM have not been previously published to our knowledge. The current study uses a mixed-methods approach to address the current gaps in literature regarding DoxyPEP implementation. By incorporating both quantitative surveys and qualitative interviews, we aim to explore the preferences, concerns, and real-world implications of DoxyPEP use among GBMSM with and without HIV in Los Angeles County.

Methods

Participant population

Men who identified as GBMSM (ages 18+ years) were recruited via email/phone from a pre-existing database of participants who agreed to be contacted for future research at the UCLA Center for LGBTQ+ Advocacy, Research, and Health. Additionally, participants were recruited via distribution of flyers to bars, clubs, and STD/HIV clinics frequented by gay and bisexual men in Los Angeles County. Sampling was both convenient and purposive in that an effort was made to enroll participants who were diverse in terms of HIV serostatus, race, and ethnicity. A total of 131 individuals completed the eligibility screener. Though our original goal was to enroll 30 participants, data collection ceased at 21 interviews as thematic saturation was reached.

Data collection

Enrolled participants (N = 21) completed a 1-h semi-structured, qualitative interview over Zoom in English between November 2023 and March 2024. Both interviewers and participants completed the remote interview from a secure location to ensure privacy. During the interviews, participants were asked questions in the following domains: prior experience with STDs, prior knowledge and awareness of DoxyPEP, interest in using DoxyPEP, preferences for accessing DoxyPEP, DoxyPEP concerns, and potential impact of DoxyPEP on sexual risk and STD prevention behaviors. Interviews were audio recorded. In addition, participants completed a brief quantitative survey that assessed condom use during sex, number of past-year sexual partners, recent history of STDs, prior awareness of DoxyPEP, preferences for accessing DoxyPEP, and demographics to provide context for qualitative findings.

Data analysis

The audio recordings of interviews were transcribed verbatim by two authors (E.A.Y. and K.A.) and analyzed in Dedoose (Version 9.0.17) using content analysis. ²⁴ All personally identifiable information was redacted from interview transcripts. A combination of deductive and inductive coding was employed. Structural codes corresponding to the interview guide and primary research question domains were created in advance of reviewing transcripts.

After preliminary examination of the data, an emergent coding approach was used to categorize the data from which thematic categories were established. Transcripts were coded by research staff (C.C.O., O.R., and K.A.) and the principal investigator (PI). Coders underwent a training period during which they learned how to correctly apply the structural codes to training transcripts, resolve coder disagreements, and discuss emerging themes. Inter-coder reliability at the code-specific level was iteratively assessed to inform revisions to the coding frame. ²⁵ After achieving code saturation and acceptable pooled inter-coder reliability on training transcripts (Cohen’s kappa > 90%), each transcript was coded and summarized independently by coders, whose work was reviewed by the PI. In addition to the quantitative measure of inter-coder reliability, we used several qualitative measures of inter-coder reliability that have been previously proposed. ^25,26

For the survey data, summary statistics (mean and standard deviation for continuous variables, and frequency/proportions for categorical variables) were calculated.

Ethics and informed consent

Certified exempt Institutional Review Board approval for the study was obtained at both UCLA and Brown University, and each participant was given ample time to review a detailed Study Information Sheet before enrollment in the study. Participants were compensated $60.

Researcher reflexivity

The study team worked to maintain a values-based approach throughout all stages of the research process, including an emphasis on cocreation with community and researcher reflexivity. Creation of the interview guide, quantitative survey, and other study materials was guided by the leadership of three senior PIs (K.B.B., K.H.M., and M.J.M.) who have decades of experience in conducting research with GBMSM. To improve trustworthiness of our interpretations of interview transcript data and navigate potential researcher bias, the coding team prioritized attaining a high level of inter-coder reliability while holding space for reasonable disagreements in perspective based on diverse past lived and academic experiences. Most of the study team worked and resided in the Los Angeles area and had cultural and geographical insight, which supported rich and nuanced analysis. Though few members of the study team would have been eligible to participate in the study themselves, the majority of the team was made up of sexual and/or gender minorities with a strong commitment to promoting health equity among marginalized communities.

Results

The current study includes 21 cisgender men who identified as gay (90%), bisexual (5%), or pansexual (5%); 33% were living with HIV. Participants’ mean age was 40 years (standard deviation [SD] = 15 years). Participants self-identified as Black or African American (43%), White (38%), mixed race/‘‘other�? (14%), and Asian (5%); of these, 48% identified as Hispanic/Latino. Almost half of the participants (43%) reported receiving a diagnosis of an STD in the past year, and the average number of past-year sexual partners was 4.5 (SD = 2.27). Additional sociodemographic characteristics are reported in Table 1.

Table 1.

Sociodemographic Characteristics, Sexual Behavior, and Other Health-Related Factors Among Gay, Bisexual, and Other Men who Have Sex with Men in Los Angeles (N = 21)

	Mean (SD)
Age	40 (15)
Number of sexual partners (past 12 months)	4.5 (2.3)

	N (%)
Current sexual identity
Gay	19 (90%)
Bi/Pansexual	2 (9.5%)
HIV status
Negative	14 (67%)
Positive	7 (33%)
Hispanic/Latinx ethnicity
Yes	10 (48%)
Race
Black or African American	9 (43%)
White or Caucasian	8 (38%)
Asian	1 (4.8%)
Mixed Race/Other	3 (14%)
Educational attainment
Some high school or less	2 (9.5%)
High school graduate or GED	3 (14%)
Completed some college	3 (14%)
Associate degree	5 (24%)
Bachelor’s degree	5 (24%)
Master’s degree or higher	3 (14%)
Employment status
Yes	15 (71%)
No	6 (29%)
Household annual income before taxes
Less than $25,000	6 (29%)
$25,000–$34,999	5 (24%)
$35,000–$49,999	5 (24%)
$50,000–$74,999	1 (4.8%)
$75,000–$99,999	2 (9.5%)
$100,000 or more	2 (9.5%)
Insurance type
Private insurance	5 (24%)
Medicaid/Medi-Cal	11 (52%)
Medicare	3 (14%)
None	2 (9.5%)
Seen a health care provider (past 12 months)
Yes	17 (81%)
No	3 (14%)
Decline to answer	1 (5%)
Bacterial STD diagnosis (past 12 months)
Yes	9 (43%)
No	12 (57%)
Level of concern about STDs
Not at all concerned	3 (14%)
Slightly concerned	3 (14%)
Moderately concerned	2 (9.5%)
Somewhat concerned	6 (29%)
Very concerned	7 (33%)
Condom use during anal sex in (past 12 months)
Always	1 (4.8%)
Sometimes	9 (43%)
Never	9 (43%)
Decline to answer	2 (9.5%)
Heard of DoxyPEP
Yes	6 (29%)
No	11 (52%)
Not sure	3 (14%)
Decline to answer	1 (4.8%)

DoxyPEP, doxycycline for post-exposure prophylaxis; SD, standard deviation; STD, sexually transmitted disease.

Below, we present the qualitative themes identified through the analysis of 21 transcripts supported by corresponding quantitative results from the brief surveys. Selected illustrative quotes are in Table 2.

Table 2.

Illustrative Participant Quotes

Section	Domain	Selected quotes (participant characteristics)
1	DoxyPEP Knowledge	“I don’t know much, I don’t think. But I also think I do know a little bit, because I think that’s the pill they give you if you actually are positive for one of those [bacterial STDs]. … I’ve been hearing recently that it can prevent STIs [sexually transmitted infections], like all together.�? (Black/African American, 35-year-old, HIV seronegative)
		“First time I heard of it [DoxyPEP], I heard you’re supposed to take it a couple of days before sexual interactions. Then I heard you’re supposed to take it after sexual interactions, almost like PEP, I think it is.�? (Black/African American, 32-year-old, HIV seronegative)
		“…It [DoxyPEP] is an antibiotic you can take after you think you’ve been exposed, or after a sexual encounter. I don’t know guidelines of its usage, but you take it after you are exposed, or have a sexual encounter, to reduce the risk of developing an STI…I hear it’s relatively safe.�? (Hispanic/Latino, 33-year-old, HIV seropositive)
2	Misconceptions about DoxyPEP	“All I remember being told was that it was a way for people, you know, post-sex to take something to address not just HIV, but, you know, bacterial infections, of STIs… I think benefits would be hoping to avoid either becoming infected, or you know, the seriousness of infection.�? (White, 59-year-old, HIV seronegative man)
		“It’s supposed to make you immune to STDs�? (Black/African American, 32-year-old, HIV seronegative)
		“I don’t know if you just need to take it once, and you’re good for like 6 months or something.�? (Asian, 26-year-old, HIV seronegative)
3	Prior DoxyPEP Experiences	“Yes, but my doctor didn’t tell me about it…a friend told me, and he gave me a couple of pills. I just haven’t used them yet, because I haven’t, you know, had an experience where I felt like, ‘oh, I should probably take it because I’m gonna be having sex with 20 guys or something.’ I just have it just in case. And I’m gonna ask my doctor about how it’s supposed to be used.�? (White, 65-year-old, HIV seropositive)
		“Yes, I know it’s doxycycline, and I know it’s taken to prevent STDs. I only found out more about it when I got the prescription for it. And they told me I would just take like one pill, one antibiotic after I do anything… They gave me 30 pills at first, but then they were like ‘that’s a little bit.’ So the next time I refilled it I got 60…Antibiotics, they can kind of be hard on your stomach. So I tried to get probiotics…I take the pill and I try to make sure that I don’t get nausea and stuff. I really don’t get it. Even when I was like taking it when I was younger [for acne] I never got nausea, but I knew it was something that can happen.�? (Hispanic/Latino, 20-year-old, HIV seronegative)
		“I’ve heard people say, ‘I’m on Doxy,’ or ‘I’m on it already,’ so I know it’s in the wave of things.�? (Black/African American, 35-year-old, HIV seronegative)
4	DoxyPEP Interest	“I think it’s great that it’s out there. I feel like it’s a wonderful drug. I feel like once it’s more available, or whatever… Once the word gets out of how people can get it and obtain it, and the resources become more available…I will be more willing to get it and try it. I think it’s a great thing, and I will probably become an advocate for it.�? (Hispanic/Latino, 33-year-old, HIV seropositive)
		“It’s going to be really helpful for everyone.�? (Hispanic/Latino, 40-year-old, HIV seropositive)
		“I would need some convincing. It has to be popular. I have to know people who have actually used it.�? (Black/African American, 28-year-old, HIV seronegative)
5	Cost/Affordability of a 1-month supply of DoxyPEP	“In a perfect world, it should be free. But we’re not there yet, so… I don’t know. I just wish it could be affordable.�? (Mixed Race, 31-year-old, HIV seronegative)
		“What’s the cost of making it?…What’s the cost of getting the medicine? And where is the money going to? If it’s just going to another pharmaceutical company, then I don’t understand why you can’t give it out for free if it’s saving lives.�? (Black/African American, 35-year-old, HIV seronegative)
		“I think probably max $20. But I know that if I’m in a position where I can’t do that…especially if you’re like doing survival sex work, or if you’re like unhoused or something like that, you might not even have 10, you know, 10 bucks to keep yourself safe, so I think free of cost would be great.�? (Asian, 26-year-old, HIV seronegative)
6	DoxyPEP Setting	Doctor  “…All these drugs are coming from different countries and stuff like that. So if you get it from like, you know, like a vending machine, or you can get it from the pharmacy, maybe could be something else? It is not gonna be the same as, you know, the medication prescribed. So it would be more safe to ask the doctor to get it, instead of getting it from outside.�? (Hispanic/Latino, 40-year-old, HIV seropositive)
		“I feel like for me, as long as I wouldn’t have to see my doctor about it, I would get it if I could get it somewhere where I didn’t have to like present to the- his office and be like ‘I have another STI. Can I get it?’, you know, as long as that doesn’t have to happen. I’d be willing to get it.�? (Hispanic/Latino, 33-year-old, HIV seropositive)
		Telehealth/Virtual  “I think that that what they should start doing this really kind of taking advantage of, like the virtual appointments with doctors…Because during Covid they always had us, you know, doing these virtual appointments with our doctors, so I think that that they made it a prescription work that they can get online through a virtual doctor or virtual appointment with a doctor that that might also be something very helpful.�? (Black/African American, Hispanic/Latino, 30-year-old, HIV seropositive)
		Vending machine  “I like the idea of it being in a vending machine. I’ve seen vending machines with like HIV tests and things of that nature…If it’s something that can help you within like 24 to 72 hours, like a Plan B pill or something like that, I think it should be offered where it can be easily accessible, so you don’t have to go through a bunch of loopholes�? (Black/African American, 35-year-old, HIV seronegative)
		“We have vending machines for soda, which are bad for your body. Why can’t we have a medicine vending machine? You know, what, ‘I fucked up. I slept with someone. I’m not gonna take a chance. Let me go to the grocery store.’ I would love that.�? (Hispanic/Latino, 55-year-old, HIV seropositive)
		Clubs/GBMSM Venues  “They should make it available to as many types of like gay venue things where sex is likely to happen… I mean, they’re they’re encouraging people to connect and have sex. That’s the whole point of the party. It’s not a dance party, it’s a sex party, so, they should be included with the price of admission…You know, like when you go in and you’re paying your money, and then they’re checking your ID, they could say, ‘Do you want DoxyPEP?’ And if you don’t know about it, they could have someone that would explain it…Or at the bar, you could ask for a dose…and since you can only get it through a prescription, I guess, have a doctor on hand to write a prescription. Or let it be available without a prescription. Isn’t there birth control things, like morning after, you don’t have to have a prescription for that.�? (White, 65-year-old, HIV seropositive)
		“Depending on the area, nightclubs could be a good venue…Especially nightclubs where you have those people who already sit in the bathroom selling shit anyways, you know?�? (Black/African American, 35-year-old, HIV seronegative)
7	Concerns about DoxyPEP	Side effects  “I’m the type of person, when it comes to side effects, I’m very- I become very serious with it when it comes to side effects.�? (Black/African American, 28-year-old, HIV seronegative)
		“I had to do a round of doxycycline proactively when I got tested for syphilis. And I’m not sure DoxyPEP is quite the same thing, but it’s a very similar medication, from what I understand. And that stuff is super powerful. I’ve never had a negative reaction to medication like that…I had like a few days left, but I didn’t really eat much that day, and then I ate it. Like I had it before I went to bed, and within like an hour and a half I had to get up and I just started puking. And it was like, weirdly uncomfortable.�? (Mixed Race, 31-year-old, HIV seronegative)
		Resistance  “Well, I think antibacterial- or bacterial resistance is probably like my biggest thing…if I’m like taking it often, you know, when I’m having like unprotected sex or hook ups with other people then I imagine, that that can’t be good, right?�? (Asian, 26-year-old, HIV seronegative)
		“My only concern would be like long term-what’s the long term with it? I know it might be effective right now, but I’m sure it has some long-term effect, and, like what happens if you really- your body really needs it for something else?�? (Black/African American, 35-year-old, HIV seronegative)
8	Risk Compensation	“I mean concerns community-wide, it seems a lot like PrEP for HIV, where once the boys had that in tow, they went crazy. And then all of a sudden, there was, you know, antibiotic resistant syphilis, or whatever…and I think it’s just one more thing that it’s gonna say to them, oh, you can do whatever you want now, despite the risks.�? (White, 59-year-old, HIV seronegative)
		“I would probably be a little bit more lenient with sex.�? (Black/African American, 35-year-old, HIV seronegative)
		“I might feel a little bit less inhibited.�? (White, 65-year-old, HIV seropositive)
		Condom Use  “I will still use a condom, even if I’m on the PrEP or the Doxy. Cause I just still want to be safe. You just never know. You just can’t take a risk. And not everybody is gonna be honest with you. And so if a person don’t wanna use a condom or use any sort of protection, I’ll have to say no, because I’m not putting my health on the line for you as it is.�? (Black/African American, 34-year-old, HIV seronegative)
		“Condoms, I don’t really like condoms. So yeah, if I had a bottle of the [Doxy]PEP? Yeah, I’m done with condoms. I’m done with them, yeah. Definitely.�? (Black/African American, 66-year-old, HIV seropositive)
		Number of Sex Partners  “I kind of feel like that it might be something that might even be overused by some people…I think that a lot of sex work, that’s gonna really start taking place and stuff like that because of the introduction [of DoxyPEP]. So I really wouldn’t be, uh, surprised, you know?�? (Black/African American, Hispanic/Latino, 30-year-old, HIV seropositive)
		“I feel like it might make me more careless only because, you know I’m protected against it– Well I’ll have more protection against it. So I mean, I have those conversations up front, you know, I may have multiple partners in a day, that type of thing. So I feel like it might up my numbers.�? (Black/African American, 32-year-old, HIV seronegative)
9	STD and HIV Combination Prevention	“I have to tell people about PEP, because of my [HIV] status, so I think it [DoxyPEP] might be something that I will probably prepare to have a little bit of too�? (Black/African American, Hispanic/Latino, 30-year-old, HIV seropositive)
		“I think as long as I’m like assured, or they like make it known that there’s no like adverse drug interaction, or, you know, taking one won’t inhibit the effectiveness of the other. Then, I wouldn’t mind taking both.�? (Asian, 26-year-old, HIV seronegative)
		“You know honestly, hopefully, it [DoxyPEP] might encourage the whole, um, pill everyday kind of aspect.�? (Black/African American, Hispanic/Latino, 30-year-old, HIV seropositive)

DoxyPEP, doxycycline for post-exposure prophylaxis; STD, sexually transmitted disease.

DoxyPEP knowledge and experiences

Knowledge of DoxyPEP in our sample was low, with only six participants (29%) having heard of it for STD prevention prior to enrollment in the current study from emails, online sources, friends, and sexual partners. Subsequently, participants’ knowledge regarding the purpose of using DoxyPEP was limited (see Table 2, Section 1), and misconceptions remained even after being educated about its use and potential for STD prevention (see Table 2, Section 2). Only two participants (9.5%) had previously used DoxyPEP as prescribed from their health care provider. One participant obtained DoxyPEP from a friend, and one participant knew of someone who has used DoxyPEP for STD prevention (Table 2, Section 3).

DoxyPEP interest

After receiving information about the use of DoxyPEP for STD prevention, potential side effects, and efficacy, most (81%) expressed either an interest in using DoxyPEP themselves and/or expressed a positive outlook on DoxyPEP use among GBMSM in general (see Table 2, Section 4). Participants expressing interest in using DoxyPEP described that they would feel an added “sense of security�? going into a sexual encounter. Two participants (9.5%) indicated having no interest in using DoxyPEP because of their negligible perceived risk for STD acquisition and dislike of oral medications in general. An additional two participants (9.5%) said they might be interested in using DoxyPEP, but they wanted more information and long-term data before making a decision.

DoxyPEP implementation preferences

Preferences for DoxyPEP implementation were assessed, including the amount they would be willing to pay for a 1-month supply and preferred setting for accessing it. A variety of different price points were assessed (see Fig. 1a), with the majority willing to pay between $10 and $20 for a 1-month supply. In interviews, participants preferred that DoxyPEP would be covered by insurance, or free/“affordable�? (see Table 2, Section 5), and almost all participants had insurance coverage (90%).

FIG. 1.

(A–C) Cost and setting preferences and level of concern regarding DoxyPEP (N = 21). (A) Maximum amount participants are willing to pay for a 1-month supply of DoxyPEP. (B) Ranked preferences for where participants would prefer to access DoxyPEP. (C) GBMSM level of concern for various domains related to DoxyPEP use. DoxyPEP, doxycycline for post-exposure prophylaxis; GBMSM, gay, bisexual, and other men who have sex with men.

The setting in which participants would want to access DoxyPEP varied (see Fig. 1b). More than half of the participants ranked accessing DoxyPEP from a doctor or over the counter at a pharmacy as their first or second preference, but for a quarter of men, obtaining DoxyPEP through a doctor’s office was least preferred due to the accompanying logistical barriers (e.g., would need to take time off from work, coordinating a ride to the clinic, etc.). The least favorable option was ordering DoxyPEP online (without seeing a doctor). More than a quarter of participants preferred a vending machine as their favored setting for accessing DoxyPEP. When asked to describe where they would prefer to access the vending machine, responses included at a grocery store, night club, bathhouse/sex club, pharmacy, health clinic, and their college campus. Though not explicitly assessed as part of the survey, during the interviews one participant suggested a pharmacy drive-through for accessing DoxyPEP and several other participants suggested venues where GBMSM are known to have sex (i.e., private sex parties, bathhouses, sex clubs, etc.), making it more convenient and applicable, especially if DoxyPEP were included with the cost of admission (Table 2, Section 6).

DoxyPEP-related concerns

In the survey, participants were asked to rate their level of concern regarding DoxyPEP across several domains (see Fig. 1c). All but two participants (90%) indicated at least some level of concern regarding side effects, primarily gastrointestinal, and possible antibiotic resistance; these were also the most commonly reported concerns mentioned during the interviews (81%). Participants described having very little to no concern about their ability to take DoxyPEP as prescribed (i.e., within 72 h after potential STD exposure) or feeling that they might be judged by others if they found out they were taking it (Table 2, Section 7).

Risk compensation

Participants were asked whether having access to DoxyPEP might impact the types of sexual behaviors that they engage in, such as changes to their condom use or number of sexual partners. The majority (57%) of participants thought that initiating DoxyPEP would lead to a decrease in condom use and/or increase in number of sexual partners; a third of participants (33%) said that there would be no change to their own sexual behaviors (Table 2, Section 8).

Two participants expressed that initiating DoxyPEP would likely lead to changes in other behaviors outside of sex, including engaging in more routine conversations with their partners about STD prevention. These participants also expressed the benefit of being able to share their DoxyPEP (“having it on-hand�?) with their sexual partners to help decrease their partners’ risk for STDs. Of participants who were HIV seronegative, only four (29%) reported current PrEP use. When asked how they think initiating DoxyPEP might impact someone’s ability to take their antiretroviral medication for HIV treatment (i.e., antiretroviral therapy) or HIV prevention (i.e., PrEP or PEP), essentially all participants thought that adherence would not be interrupted, but might actually improve (e.g., being more aware of taking medications surrounding their sexual health) (see Table 2, Section 9).

Discussion

The current study provides insights regarding DoxyPEP for bacterial STD prevention among mixed HIV serostatus GBMSM in Los Angeles. Most participants indicated being very interested in using DoxyPEP after learning about its potential, particularly if they could obtain DoxyPEP at no or low cost and if DoxyPEP had no side effects, reflecting an openness to adopting new STD prevention practices, which is congruent with findings from prior studies. ^{15 –19,21} However, preferences regarding the setting for DoxyPEP implementation varied. The heterogeneity of preferences for DoxyPEP implementation found suggests that a multi-modal access/distribution approach tailored to individual preference and community needs could be key to enhancing acceptability and feasibility of use, as has been recommended for PrEP implementation. ²⁷

Though the men in our study were generally interested in using DoxyPEP for STD prevention, they commonly noted concerns about side effects. Side effects from doxycycline are generally well-tolerated, ⁸ but our qualitative data suggest that it may deter some individuals from using it regularly. The high level of concern regarding side effects is a potential barrier to the introduction of DoxyPEP into routine STD prevention, necessitating transparent communication about potential short- and long-term adverse effects and how they can be managed, including for those already managing complex regimens for HIV or other health conditions. ^19,28

The concerns about antimicrobial resistance among participants echo broader public health apprehensions about potential drug resistance from the widespread prescription and use of antibiotics for STD prevention. Assessing the potential for antibiotic resistance has been a priority in DoxyPEP randomized controlled trials, which have thus far found low or no risk of antimicrobial resistance. ^14,15 The concerns about antimicrobial resistance, while valid, should not overshadow the potential benefits of DoxyPEP for high-risk populations, and additional longitudinal research and surveillance of DoxyPEP and antimicrobial resistance is needed. ²⁹

Risk compensation was a concern among several participants, which was unsurprising and similar to prior reports regarding HIV PrEP-related risk compensation. ^{30 –35} However, there were some participants who believed DoxyPEP could encourage safer sexual practices, including through improved communication with sexual partners about HIV and STD prevention. Participants noted that DoxyPEP could be an additional prevention tool to have “on-hand�? for sexual encounters and to share with sexual partners, potentially empowering men to have more intentional conversations about risk reduction with their partners, and suggesting that peer/partner education could play a role in effective implementation of DoxyPEP. In addition to the potential for sharing with sexual partners, sharing DoxyPEP with friends was also described by men in our study. Though individuals who share HIV/STD prevention medications (i.e., PrEP, DoxyPEP) in casual settings with friends and sexual partners likely have positive intentions stemming from the desire for self and community protection, there are potential dangers that must be addressed, including unintended side effects and potential medication interactions. ³⁶

Despite the high prevalence of recent STD diagnoses in our study population, prior knowledge about DoxyPEP was low. Significantly, participants who had heard of DoxyPEP reported their source of information was via online media or friends, suggesting that careful and accurate reporting on the outcomes of DoxyPEP safety and efficacy trials is necessary to ensure proper use and understanding among GBMSM, particularly since completed trials show partial efficacy, and the fact that behavioral risk compensation could obviate the moderate protective benefits from this medication. Further, misconceptions were common, with the most concerning one that remained (even after being educated about its use and potential value) being the incorrect notion that DoxyPEP is effective at preventing STDs and HIV. This misconception, coupled with our finding of high potential for risk compensation (decreasing condom use, increasing number of sexual partners, etc.) among DoxyPEP users, may inadvertently increase sexual risk for HIV. Public health initiatives should focus not only on increasing awareness but also clarifying the limitations of DoxyPEP, emphasizing comprehensive prevention strategies, including condom use, PrEP/PEP for HIV, and routine STD/HIV testing.

Before enrolling in the research study, most of our sample had not heard of DoxyPEP, and at least half of our HIV seronegative participants were not currently using PrEP. In many clinical settings, DoxyPEP is now commonly offered to people on PrEP, and so the low experience with DoxyPEP in our sample could be a reflection of our largely PrEP-naïve sample. This is an important consideration, as the majority of our sample was racially and ethnically diverse and at risk for HIV and STDs. They and others like them may be missing out on two important sexual health prevention interventions, both DoxyPEP and PrEP. The reason for lack of PrEP use in our population is not immediately clear based on the data we collected in the study, as most men reported visiting a doctor in the past year and all reported anal sex with another man in the past year. It is possible that not all of the men in our study share their sexual orientation with their provider, or that they are seeing a health care provider for reasons not related to sexual health. Another possibility is that some of the PrEP-naïve men in our study are in monogamous sexual relationships with a partner who is HIV seronegative. These are all factors that should be considered in order to ensure that sexual health prevention interventions are reaching populations most impacted by HIV/STDs.

Our study had some limitations. Given how recently the CDC guidelines were published for DoxyPEP in relation to when interviews were conducted, the majority of participants had no experience taking the medication. Participant responses were based on anticipated and perceived behavior. In the quantitative survey, we asked participants how much they would be willing to pay for a 1-month supply of DoxyPEP. Because DoxyPEP is used on an as-needed basis, a 1-month supply could look different for each participant. For example, someone with a daily exposure may need 28 doses in a month, while another person may only take one or two doses per month. Future research should operationalize this measure by number of doses rather than monthly supply to capture these variations in use. Though the quantitative data is helpful in providing context for our results, the study is not powered for statistical comparisons (such as between people living with and without HIV). Further, as our study included only cisgender men living in Los Angeles, generalization of our findings to other regions of the United States may not be appropriate, and future research should investigate DoxyPEP preferences among transgender men and women to ensure equitable implementation across diverse populations.

Our study highlights both the promise and challenges associated with implementing DoxyPEP among GBMSM in Los Angeles. While there is strong interest in using DoxyPEP, concerns about side effects, antimicrobial resistance, risk compensation, cost, accessibility, and misconceptions surrounding its use present important barriers to its widespread adoption. A tailored, multi-modal, and comprehensive approach that takes into account individual and community needs, alongside robust educational campaigns, is essential to ensuring successful implementation of DoxyPEP as an efficacious STD prevention method.

Authors’ Contributions

E.A.Y., M.J.M., K.B.B., and K.H.M. designed the interview guide and quantitative surveys and the research and conceptualization that led up to it. E.A.Y., C.C.O., and O.R. wrote the first draft of the article. E.A.Y., C.C.O., O.R., and K.A. conducted the qualitative coding and content analysis. E.A.Y. conducted the quantitative analysis. All other authors contributed to the study operations and reviewed, edited, and approved the final article. All authors accept responsibility for the publication of this article.

Author Disclosure Statement

The authors have no conflicts of interest to disclose.

Funding Information

Research reported in this publication was supported by two Rapid Response Grants from the UCLA-CDU Center for AIDS Research (CFAR; AI152501) and the Providence/Boston CFAR at Brown University (P30AI042853) to M.J.M. and K.B.B., respectively. The content is solely the responsibility of the authors and does necessarily represent the official views of the CFARs or National Institutes of Health.