Purpose of This Guideline
Date of current publication: October 15, 2024
Lead authors:
Daniela E. DiMarco, MD, MPH; Marguerite A. Urban, MD
Writing group: Rona M. Vail, MD, AAHIVS; Sanjiv S. Shah, MD, MPH, AAHIVM, AAHIVS; Steven M. Fine, MD, PhD; Joseph P. McGowan, MD, FACP, FIDSA, AAHIVS; Samuel T. Merrick, MD, FIDSA; Asa E. Radix, MD, MPH, PhD, FACP, AAHIVS; Jessica Rodrigues, MPH, MS; Brianna L. Norton, DO, MPH; Charles J. Gonzalez, MD; Christopher J. Hoffmann, MD, MPH, MSc, FACP
Committee:
Medical Care Criteria Committee
Date of original publication: September 25, 2023
This guideline on the use of doxycycline post-exposure prophylaxis (doxy-PEP) for prevention of bacterial sexually transmitted infections (STIs), including syphilis, chlamydia, and gonorrhea, was developed by the New York State Department of Health AIDS Institute (NYSDOH AI) Clinical Guidelines Program to support clinicians caring for adults and adolescents with and without HIV who are at risk of acquiring STIs. The goals of this guideline are to:
Summarize the available evidence regarding the use of doxy-PEP for preventing syphilis, chlamydia, and gonorrhea infections
Provide evidence-based clinical recommendations for the use of doxy-PEP
Present practical considerations for prescribing doxy-PEP
The literature on this topic is evolving rapidly, with several clinical trials ongoing. To prepare this guideline, the authors conducted a review of the published literature through MEDLINE, conference presentations, and existing published guidance within the United States and internationally.
Biomedical Prevention of STIs
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| RECOMMENDATIONS |
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Biomedical Prevention of STIs
Clinicians should offer doxy-PEP to cisgender men and transgender women who engage in condomless sex with partner(s) assigned male sex at birth and who:
Have had a bacterial STI diagnosed within the past year (A1), or Have no or unknown history of STIs and ongoing risk of STI exposure (A2)
Clinicians should engage in shared decision-making with cisgender men who are at ongoing risk of STI exposure and engage in condomless sex with multiple partners assigned female sex at birth, offering doxy-PEP on a case-by-case basis. (B3) When prescribing doxy-PEP, clinicians should use the dosing regimen of oral doxycycline 200 mg taken ideally within 24 hours (up to 72 hours) after condomless sex (A1) and counsel patients (A*) on the key points for patient education outlined in Table 1: Considerations for Doxy-PEP Implementation. For individuals taking doxy-PEP, clinicians should screen for HIV, chlamydia, gonorrhea, and syphilis at least every 3 months. (A1) Clinicians should offer HIV PrEP to individuals who do not have HIV and are initiating or using doxy-PEP. (A*) Clinicians should offer HIV treatment to individuals with HIV who are not on antiretroviral therapy and are initiating or using doxy-PEP. (A1)
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Abbreviations: doxy-PEP, doxycycline post-exposure prophylaxis; PrEP, pre-exposure prophylaxis; STI, sexually transmitted infection.
The United States, including New York State, continues to see high rates of reportable STIs, specifically syphilis, chlamydia, and gonorrhea [CDC(b) 2024], despite decades of public health efforts and prevention strategies aimed at curbing the STI epidemic. Some populations, including men who have sex with men (MSM), young people, and some racial and ethnic minority groups, are disproportionately affected by STIs [CDC(b) 2024]. Centers for Disease Control and Prevention (CDC) STI surveillance data from 2022 note that reportable STIs continue to disproportionately affect people who identify as Black/African American and American Indian/Alaska Native [CDC(b) 2024], making clear that established STI prevention strategies are insufficient.
Biomedical methods for HIV prevention with HIV PrEP and PEP have been very effective. Researchers identified doxycycline as a candidate for biomedical prevention of STIs. In 2011, Wilson and colleagues used mathematical modeling based on sexual behavior factors to predict doxy-PEP efficacy among MSM in Australia. Assuming 50% uptake and 70% efficacy, the model predicted a 50% reduction in syphilis cases after 1 year and an 85% reduction after 10 years [Wilson, et al. 2011]. Doxycycline is an antibiotic in the tetracycline class and is approved by the U.S. Food and Drug Administration for the management of many different types of infections [Lexicomp 2023; FDA 2016]. Doxycycline is available in 2 different formulations: hyclate, which is more water soluble, and monohydrate, which is less water soluble so may have fewer gastrointestinal adverse effects. Common uses include treatment of chlamydia, syphilis, respiratory infections, and skin and soft tissue infections. Doxycycline has also been used as both a PrEP and PEP agent for certain bacterial and parasitic infections, including Lyme disease, leptospirosis, and malaria [Grant, et al. 2020].
When used in nonpregnant adults, doxycycline is safe and well tolerated, has excellent oral bioavailability, is low cost, and is widely available. Adverse effects of doxycycline are generally mild, with gastrointestinal symptoms being the most common. Other adverse effects include photosensitivity and esophageal injury. Doxycycline is contraindicated in pregnancy because of potential adverse effects on the fetus [Lexicomp 2023]. Doxycycline is also used safely for prolonged periods for some conditions, including acne [Zaenglein, et al. 2016] and prosthetic joint infections [Osmon, et al. 2013]. A systematic review and meta-analysis evaluated the safety of long-term (8 weeks or more) doxycycline use for treatment or prevention of a variety of conditions, identifying 67 studies for analysis over a 20-year period ending in January 2023 [Chan, et al. 2023]. Nearly one-third of the studies reported mild to moderate adverse effects, most frequently gastrointestinal and dermatologic. Severe adverse effects were uncommon. These factors make doxycycline a promising prophylactic agent; however, the effects on antimicrobial resistance and the microbiome with widespread use are still under investigation.
Doxycycline as PEP
Available evidence on doxy-PEP to prevent bacterial STIs is limited but increasing. Current data are from randomized clinical trials, observational studies, modeling studies, and surveys on acceptability for use. Studies predominantly included cisgender men and transgender women who have sex with men, were receiving HIV PrEP or in care for HIV infection, were aged 35 years and older, and were White.
In 4 randomized clinical trials comparing doxy-PEP with standard of care (routine STI testing), participants received HIV PrEP or HIV care, and in 3 of the 4 trials participants had a history of ≥1 bacterial STI in the prior year. The study protocols used oral doxycycline 200 mg taken ideally within 24 hours or up to 72 hours of condomless sex to prevent bacterial STIs. All participants were tested for STIs every 3 months during the study period [Molina, et al. 2024; Luetkemeyer, et al. 2023; Stewart, et al. 2023; Molina, et al. 2018]. In the 3 trials conducted among cisgender men and transgender women who have sex with men, there were significant reductions in chlamydia and syphilis, but results were mixed regarding the efficacy of doxy-PEP in preventing gonococcal infections, likely at least in part because of geographic variability in prevalence of tetracycline resistance in gonococci [Molina, et al. 2024; Luetkemeyer, et al. 2023; Fairley and Chow 2018; Molina, et al. 2018; Siguier and Molina 2018]. In a study that included only cisgender women taking HIV PrEP, doxy-PEP was not effective at preventing bacterial STIs [Stewart, et al. 2023].
A modeling study analyzed data from an LGBTQ-focused health center in the United States to assess the effect of doxy-PEP use on STI incidence among more than 10,000 individuals assigned male sex at birth (including cisgender men, transgender women, and nonbinary individuals) who had male sex partners and STI testing (chlamydia, gonorrhea, or syphilis) on record [Traeger, et al. 2023]. STI incidence was 35.9 per 100 person-years. Modeling demonstrated that, rather than prescribing doxy-PEP based solely on HIV or PrEP engagement, prescribing based on STI history resulted in an efficient strategy that balanced uptake and preventive impact. An approach combining these factors, as was done in the clinical trials, was not modeled in this projection. Seven different strategies for prescribing doxy-PEP over 12 months were modeled [Traeger, et al. 2023]. Prescribing to all in the sample, an estimated 71% of gonorrhea, chlamydia, and syphilis cases could have been averted (number needed to treat [NNT] for 1 year to avert 1 STI diagnosis of 3.9). Prescribing to individuals with HIV (12%) or who were taking HIV PrEP (52%) could have averted 60% of STI diagnoses in this group (NNT of 2.9). Limiting prescribing to individuals with an STI diagnosis, the proportion using doxy-PEP was reduced to 38% and would have averted 39% of STI diagnoses (NNT of 2.4).
This committee’s recommendations on provision of doxy-PEP are outlined above, and implementation considerations are discussed in the guideline section Practical Considerations for Doxy-PEP Implementation. The risk-benefit profile for doxy-PEP is expected to vary based on individual patient factors and community and sexual network STI prevalence. Factors associated with increased likelihood of STI exposure include having multiple sex partners, engaging in group sex, engaging in transactional sex, and combining sex and substance use [Workowski, et al. 2021]. An individualized assessment is an important aspect of shared decision-making between patient and clinician.
The A-level recommendations for doxy-PEP use among cisgender men and transgender women who have sex with men are based on the significant reductions in bacterial STIs reported in the 3 clinical trials [Molina, et al. 2024; Luetkemeyer, et al. 2023; Molina, et al. 2018], described in detail below, and post-implementation observational data [Sankaran, et al. 2024; Scott, et al. 2024]. Although the majority of STIs among these populations are asymptomatic and without complications, the significant decrease in STI occurrence provides potential benefits to individuals and the broader community and likely outweighs the potential harms of doxycycline use. Based on the lack of efficacy reported for doxy-PEP in cisgender women in Kenya [Stewart, et al. 2023] , there is insufficient evidence to recommend its use in individuals at risk of STIs through receptive vaginal sex. However, hair samples examining doxycycline levels point to possible adherence issues [Stewart, et al. 2023], and pharmacologic data from an unrelated study suggest adequate tissue and secretion levels for protection [Haaland, et al. 2023].
There are no published data evaluating doxy-PEP use among cisgender men with sex partners assigned female sex at birth. However, doxy-PEP use among cisgender men (with female sex partners) who have similar STI risk factors as the doxy-PEP study populations (i.e., history of STIs, multiple sex partners, high-prevalence populations) could also potentially provide individual and community benefits outweighing the risks of doxycycline use. The NNT and degree of potential protective effect with insertive vaginal sex are unknown. This strategy has the possibility of indirectly extending the potential benefits of doxy-PEP use to cisgender women (who have sex with men) and to neonates, who experience the majority of complications of bacterial STIs, through reduction of community rates and may be considered by clinicians on a case-by-case basis. Doxy-PEP has not been studied in adolescents younger than 18 years, and adherence and efficacy in this group are unknown.
Evidence from the IPERGAY trial: The first published evidence on doxy-PEP was derived from a substudy of the ANRS IPERGAY randomized trial of on-demand HIV PrEP among cisgender men and transgender women who have sex with men in France. The substudy demonstrated an approximately 70% reduction in incident chlamydia and syphilis infections but no significant reduction in gonorrhea infections in a population reporting sex practices placing them at high risk of STIs [Molina, et al. 2018]. In this open-label extension, more than 200 participants (cisgender men and transgender women who have sex with men) taking HIV PrEP were randomized to receive doxycycline hyclate 200 mg as a single dose within 24 to 72 hours after condomless sex or no doxy-PEP. Study participants were mostly White, aged 30 years and older, and reported having multiple sex partners (10 in 2 months) and engaging in condomless sex acts (10 in 4 weeks). Participants were instructed not to exceed 3 doses per week; the median number of doxy-PEP doses used per month was 3.4, which was fewer than the number of reported condomless sexual encounters. Of participants, 83% took doxy-PEP within 24 hours of sex. Gastrointestinal adverse effects were reported by more than half of the participants, resulting in 8 discontinuations. Doxy-PEP was associated with significant reductions in the incidence of first STI and, in individual analyses, of incident chlamydia and syphilis infections. For incident gonorrhea, however, there was no significant reduction in the doxy-PEP group, which was attributed to the high prevalence of tetracycline resistance among gonococcal isolates in France.
Evidence from the DoxyPEP trial: The open-label randomized DoxyPEP study analyzed data from 501 adult cisgender MSM (96%) and transgender women who have sex with men (4%) who were either taking HIV PrEP (n = 360) or had HIV (n = 194) and who had a bacterial STI and reported condomless sex with a male partner within the past year. Participants were randomized to receive either doxy-PEP as 200 mg of delayed-release doxycycline hyclate (ideally within 24 hours but no later than 72 hours after condomless sex) or standard of care [Luetkemeyer, et al. 2023]. STI testing was performed every 3 months over 1 year of follow-up. Participants had a high prevalence of baseline bacterial STIs and a median of 9 sex partners in the 3 months before enrollment, and 59% reported substance use. The median participant age was 38 years, and 67% were White, 7% were Black, 11% were Asian or Pacific Islander, 15% were multiracial or other, and 30% were Hispanic or Latino. The maximum dose of doxycycline was 200 mg within a 24-hour period, and the medication was dispensed at 3-month intervals. The initial doxycycline supply included enough tablets for daily use, and the amount dispensed each quarter was adjusted in follow-up based on frequency of sex and doses used.
The DoxyPEP study was stopped early after interim analysis noted a significant protective effect in the intervention arm, and participants in the standard-of-care group were offered doxy-PEP [Luetkemeyer, et al. 2023]. Modified intention-to-treat analysis included participants who completed a median of 9 months of follow-up. Gonorrhea was the most common STI diagnosed, and there were very few cases of early syphilis. Median doxy-PEP use was 4 doses per month, with 25% of participants reporting more than 10 doses per month. This study demonstrated a 52% quarterly reduction in any incident STI among participants with HIV (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.28-0.83), and a 66% reduction among those taking HIV PrEP (HR, 0.34; 95% CI, 0.23-0.51) [Luetkemeyer, et al. 2023; Luetkemeyer, et al. 2022; SFDPH 2024]. Among participants taking HIV PrEP, the relative risk (RR) of any incident STI was 0.34 (95% CI, 0.24-0.46; P<.001), and the NNT was 4.7, whereas among participants with HIV, the RR for any incident STI was 0.38 (95% CI, 0.24-0.60; P<.001), and the NNT was 5.3 [Luetkemeyer, et al. 2023].
In subgroup analyses, among participants taking HIV PrEP, the significant risk reduction was maintained for each STI individually, including infections at extragenital sites, except for pharyngeal chlamydia [Luetkemeyer, et al. 2023]. Among participants with HIV, doxy-PEP did not significantly reduce incident early syphilis or urethral or pharyngeal chlamydia or gonorrhea. Doxycycline was well tolerated, and self-reported adherence was high. Antimicrobial resistance was also evaluated in this study and is discussed below (see guideline section Antimicrobial Resistance, below).
Evidence from the DOXYVAC trial: In the phase III randomized 2×2 factorial designed DOXYVAC trial, the efficacy of both doxy-PEP for bacterial STI prophylaxis and meningococcal serotype B vaccination for preventing gonococcal infection was investigated among 446 cisgender men and transgender women who have sex with men taking HIV PrEP in France [Molina, et al. 2024]. Participants were predominantly White, had a median age of 40 years, were long-term HIV PrEP users, reported multiple sex partners, and had multiple prior STIs. Unblinded early interim analysis revealed significant reductions in any incident STI, and participants were all offered doxy-PEP. Doxy-PEP significantly reduced the incidence of the first episode of chlamydia (adjusted HR [aHR], 0.14; 95% CI, 0.09-0.23; P<.0001), syphilis (aHR, 0.21; 95% CI, 0.11-0.41; P<.0001), and gonorrhea (aHR, 0.67; 95% CI, 0.52-0.87; P=.0025) infections. Self-reported adherence was high in this study at more than 70% (detectable concentrations in plasma and urine were more than 60% in the doxy-PEP group at 6 months), with a median use of 3 doses per month and a median time to doxy-PEP intake after sex of 15 hours. Additionally, antimicrobial resistance was analyzed and is discussed below (see guideline section Antimicrobial Resistance, below).
Doxy-PEP and receptive vaginal sex: Data from a randomized trial in Kisumu, Kenya, that compared doxy-PEP with the standard of care among cisgender women aged 18 to 30 years taking HIV PrEP found that doxy-PEP was not effective for bacterial STI prevention in this population [Stewart, et al. 2023]. The study enrolled 449 participants from 2020 to 2022, with very little loss to follow-up. At baseline, 18% of participants were diagnosed with an STI (14% with chlamydia, 4% with gonorrhea, and <1% with syphilis). Adherence by self-report demonstrated at least 80% of condomless sex encounters were covered, with almost all doses taken within 24 hours of condomless sex. Incident STIs were similar between groups (annual incidence of 27%), with no significant reduction in the doxy-PEP group. No incident HIV infections were reported. Fifty participants (22%) in the doxy-PEP group were randomly selected for hair sampling to assess doxycycline concentrations using an assay developed by study investigators; in this subgroup, doxycycline was detected in the hair of 56% of participants on at least 1 visit and in 32.6% on all visits for which hair specimens were collected (58/178 total visits) [Stewart, et al. 2023]. The investigators reported that a study to validate the assay with intermittent dosing of doxycycline is in development [Kojima and Klausner 2024].
The reason for the lack of demonstrable efficacy of doxy-PEP in this study is unclear. Possible factors influencing these results include the prevalence of high-level tetracycline resistance among gonococcal isolates in Kenya [Soge, et al. 2023], adherence being less than what was ascertained by self-report, and biologic or anatomic differences. An unrelated study in the United States evaluated drug concentrations with event-driven oral dosing and showed that 200 mg of doxycycline hyclate achieved concentrations above minimum inhibitory concentrations (MICs) for syphilis, chlamydia, and gonorrhea in rectal, vaginal, and cervical tissues as well as rectal and vaginal secretions; these concentrations were sustained at least 2 days after dosing, although the degree above MIC was much lower for Neisseria gonorrhoeae [Haaland, et al. 2023]. Higher doxycycline concentrations were sustained for a longer duration in rectal secretions than in vaginal secretions, although the levels remained above the MIC.
Additional studies on doxy-PEP to prevent STIs through receptive vaginal sex are in development.
Doxy-PEP post-implementation: In a large sexual health clinic setting in San Francisco, California, following the release of the DoxyPEP trial results, all individuals on HIV PrEP were offered doxy-PEP (approximately 3,000 patients). At 9-month follow-up there was approximately 39% uptake of doxy-PEP [Scott, et al. 2024]. Baseline incidence rates for any STI (gonorrhea, chlamydia, syphilis) were approximately 3 times higher in the doxy-PEP group than in the group not on doxy-PEP. By the last quarter of the study period, STI incidence rates in the doxy-PEP group were significantly reduced and comparable to those in the no-doxy-PEP group, although the reduction was not significant for the individual outcome of gonorrhea [Scott, et al. 2024]. These results demonstrate not only the effect of doxy-PEP on preventing STIs but also the STI risk stratification of individuals by self-selection of who accepted or declined doxy-PEP.
The same investigators tracked quarterly numbers of new patients starting doxy-PEP and examined the effect of doxy-PEP with early implementation on local STI epidemiology [Sankaran, et al. 2024]. It was concluded that early release of guidance and implementation for doxy-PEP at high-volume clinics was associated with substantial reductions in reported cases of chlamydia and early syphilis for just over 1 year among cisgender men and transgender women with sex partners assigned male sex at birth (an approximately 50% drop for each); notably, there was no community impact on gonococcal infections [Sankaran, et al. 2024]. The investigators noted that other factors, including changes in sex practices and activities in response to mpox, might have affected the results, although the results were sustained into 2023 [Sankaran, et al. 2024].
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| KEY POINTS |
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Doxy-PEP is not 100% effective in preventing bacterial STIs. There is insufficient evidence to recommend doxy-PEP to protect against STI acquisition through receptive vaginal sex. If doxy-PEP is used in individuals who may become pregnant, pregnancy testing should be performed, as doxycycline use should generally be avoided during pregnancy. It is essential to provide counseling and education to patients on the limitations of doxy-PEP and to emphasize that ongoing condom use and engagement in sexual health services is necessary, including but not limited to routine STI screening, STI testing for symptomatic patients, and STI treatment or evaluation after an STI exposure. Evaluation by a clinician after a known or possible STI exposure is necessary to determine whether treatment is needed. For individuals using doxy-PEP who are diagnosed with gonorrhea, chlamydia, or syphilis, treat according to the recommendations in the CDC STI Treatment Guidelines.
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Antimicrobial Resistance
Published research, previous guideline statements, and editorials have raised concerns about the impact of doxy-PEP on the emergence of antimicrobial resistance for bacterial STIs and other non-STI pathogens with widespread long-term use [Molina, et al. 2024; Cornelisse, et al. 2023; Luetkemeyer, et al. 2023; Kohli, et al. 2022; Lewis 2022; Luetkemeyer, et al. 2022; Grant, et al. 2020; Molina, et al. 2018; Siguier and Molina 2018; Golden and Handsfield 2015]. Increasing antimicrobial resistance is a concern at both the individual and population levels [Cornelisse, et al. 2023]. It may take years to determine this effect, and additional research is needed [Siguier and Molina 2018]. To date, studies of doxy-PEP have not found detectable resistance in Treponema pallidum or Chlamydia trachomatis strains [Cornelisse, et al. 2023]. Doxycycline resistance is already a concern for other bacterial STIs, including M. genitalium and N.
gonorrhoeae, and there are few alternative therapeutic options for M. genitalium [Workowski, et al. 2021]. Tetracycline (used as a surrogate for doxycycline) resistance in N. gonorrhoeae isolates varies geographically and is reported at 20.1% nationwide by the CDC Gonococcal Isolate Surveillance Project [CDC(b) 2024].
Doxycycline is an important antibiotic used to treat non-sexually transmitted infections when other oral treatment options are severely limited, including methicillin-resistant Staphylococcus aureus (MRSA). Doxycycline also remains an option for antimicrobial-resistant gonococcal infections if susceptibility is confirmed. The benefits of widespread use of doxycycline must be weighed against the known and potential risks of selecting for antimicrobial resistance and altering the various microbiomes (e.g., gastrointestinal, vaginal, skin). In an analysis of more than 2,000 gonococcal isolates in Europe, the presence of 2 common tetracycline-associated mutations was strongly associated with additional mutations conferring cross-resistance to other antibiotics, including beta-lactams, macrolides, and fluoroquinolones [Vanbaelen, et al. 2023]. This raises concern that selecting for gonorrhea tetracycline resistance may also impact the effectiveness of other antibiotic classes, including cephalosporins, which are the standard of care for gonorrhea treatment.
To assess the impact of doxy-PEP use on antimicrobial resistance, nares and oropharynx specimens were examined for S. aureus in the DoxyPEP study [Luetkemeyer, et al. 2023], and tetracycline resistance in extended-spectrum beta-lactamase (ESBL) Escherichia coli (as a marker of microbiome influence) and MRSA were assessed in the DOXYVAC study [Molina, et al. 2024]. In the DoxyPEP study, cultures were available for 17.2% of gonorrhea infections (n = 44) [Luetkemeyer, et al. 2023]. Of these, baseline tetracycline resistance (a surrogate for doxycycline resistance) was 27%. After enrollment, resistance was 38% in the doxycycline groups and 12% in the standard-of-care groups, and doxy-PEP appeared less protective for tetracycline-resistant gonorrhea, although the sample size was small [Luetkemeyer, et al. 2023; Luetkemeyer, et al. 2022]. S. aureus was cultured from the oronasopharynx in 45% of participants, and baseline doxycycline resistance was 12% [Luetkemeyer, et al. 2023]. At 1 year, S. aureus colonization identified by culture was significantly less in the doxy-PEP groups than the standard-of-care groups, and prevalence of doxycycline-resistant isolates was 16% in the doxycycline groups and 8% in the standard-of-care groups [Luetkemeyer, et al. 2023].
In the DOXYVAC study, baseline tetracycline resistance was found in all 78 specimens for which gonorrhea cultures were available, and the prevalence of high-level resistance was greater in the doxy-PEP group (36%) than in the standard-of-care group (13%); no C. trachomatis resistance was detected by culture or sequencing [Molina, et al. 2024]. As markers for assessing the impact of doxy-PEP on the microbiome, there was no significant difference between the groups in detection of ESBL E. coli from anal swabs or MRSA from the pharynx.
Based on these data, the efficacy of doxy-PEP for gonorrhea is expected to differ depending on the prevalence of tetracycline resistance in a given population or geographic region. For S. aureus, doxy-PEP is associated with increased resistance [Luetkemeyer, et al. 2023], which is an important consideration in the preservation of antimicrobial treatment options for MRSA infection.
Recommendations Outside of New York State
Several organizations have issued guidance regarding the use of doxy-PEP [Bachmann, et al. 2024; Cornelisse, et al. 2024; Werner, et al. 2024; CDPH 2023; Gandhi, et al. 2023; NCSD 2023; PHSKC 2023; SCPHD 2023; Kohli, et al. 2022; SFDPH 2024]. There is variability regarding implementation of this intervention, although dosing recommendations and the guidance to bundle doxy-PEP with comprehensive sexual health services have been uniformly consistent with studies to date.
The British Association for Sexual Health and HIV and the UK Health Security Agency do not endorse the use of doxycycline as prophylaxis, primarily because of concerns regarding antimicrobial resistance and limited long-term data [Kohli, et al. 2022]. The Australian Society for HIV, Viral Hepatitis, and Sexual Health Medicine recommends use of doxy-PEP primarily for the prevention of syphilis among gay, bisexual, and other men who have sex with men [Cornelisse, et al. 2024]. Disagreements noted are centered around the risks and benefits at the individual and population levels, including the potential for selection of antimicrobial resistance and impact on the microbiome [Cornelisse, et al. 2024; Kohli, et al. 2022]. The German STI Society released a position statement recommending against broad implementation of doxy-PEP (without further data regarding antimicrobial resistance), although they cited situations in which doxy-PEP use may be considered on a case-by-case basis [Werner, et al. 2024].
The San Francisco Department of Public Health (SFDPH) released the first set of guidelines on doxy-PEP use, recommending doxy-PEP for cisgender men and transgender women who meet 2 eligibility criteria outlined in the DoxyPEP study: 1) have a diagnosis of a bacterial STI within the last year, and 2) report condomless sex with at least 1 male partner in the past year [SFDPH 2024]. The SFDPH also recommends offering doxy-PEP via shared decision-making to cisgender men, transgender men, and transgender women who have had multiple sex partners assigned male sex at birth within the past year, even in the absence of a prior STI diagnosis. The SFDPH dosing and prescribing recommendations are the same as those used in the DoxyPEP study; however, the SFDPH notes that immediate- or extended-release doxycycline could be used, although the extended-release formulation may be more expensive. The California Department of Health (CDPH) sent out a Dear Colleague Letter on April 28, 2023, with recommendations on doxy-PEP [CDPH 2023]. The CDPH recommends doxy-PEP for cisgender men or transgender women with 1 or more bacterial STI in the past 12 months and suggests offering doxy-PEP via shared decision-making to all nonpregnant individuals at increased risk of STI acquisition, even if there is no history of an STI diagnosis. To date, there are 3 states in total with guidance on provision of doxy-PEP to any individual at risk for STIs: California [CDPH 2023], Minnesota [MDH 2024], and New Mexico [NMDPH 2023].
Public Health–Seattle and King County (PHSKC) recommends that clinicians engage in shared decision-making on doxy-PEP with cisgender men and transgender women with history of an STI in the past year and ongoing sex encounters with partners assigned male sex at birth [PHSKC 2023]. The PHSKC guidance also recommends stronger consideration for individuals in this population with a specific history of syphilis or multiple STIs in the prior year and that clinicians consider prescribing doxy-PEP episodically when patients anticipate their STI exposure risk to be elevated (e.g., group sex events).
In 2024, the CDC released formal guidelines on the use of doxy-PEP [Bachmann, et al. 2024]. For cisgender men and transgender women who have had a bacterial STI in the past year and have sex partners assigned male sex at birth, the CDC recommends providing counseling about doxy-PEP and offering this prevention strategy via shared-decision making. Comprehensive sexual health services, including STI prevention counseling, STI screening, immunizations, and linkage to HIV prevention and treatment, are also recommended.
The National Coalition of STD Directors released a doxy-PEP implementation toolkit with basic guidance on community engagement, workflow, education, program evaluation, and prescribing logistics [NCSD 2023]. Highlights from the toolkit emphasize ensuring equitable criteria for offering doxy-PEP and reducing unnecessary access restrictions.
Created: September 2023; Last Update: October 2024.
