Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections.

BACKGROUND: Interventions to reduce sexually transmitted infections (STIs) among men who have sex with men (MSM) are needed. METHODS: We conducted an open-label, randomized study involving MSM and transgender women who were taking preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) infection (PrEP cohort) or living with HIV infection (persons living with HIV infection [PLWH] cohort) and who had had Neisseria gonorrhoeae (gonorrhea), Chlamydia trachomatis (chlamydia), or syphilis in the past year. Participants were randomly assigned in a 2:1 ratio to take 200 mg of doxycycline within 72 hours after condomless sex (doxycycline postexposure prophylaxis) or receive standard care without doxycycline. STI testing was performed quarterly. The primary end point was the incidence of at least one STI per follow-up quarter. RESULTS: Of 501 participants (327 in the PrEP cohort and 174 in the PLWH cohort), 67% were White, 7% Black, 11% Asian or Pacific Islander, and 30% Hispanic or Latino. In the PrEP cohort, an STI was diagnosed in 61 of 570 quarterly visits (10.7%) in the doxycycline group and 82 of 257 quarterly visits (31.9%) in the standard-care group, for an absolute difference of -21.2 percentage points and a relative risk of 0.34 (95% confidence interval [CI], 0.24 to 0.46; P<0.001). In the PLWH cohort, an STI was diagnosed in 36 of 305 quarterly visits (11.8%) in the doxycycline group and 39 of 128 quarterly visits (30.5%) in the standard-care group, for an absolute difference of -18.7 percentage points and a relative risk of 0.38 (95% CI, 0.24 to 0.60; P<0.001). The incidences of the three evaluated STIs were lower with doxycycline than with standard care; in the PrEP cohort, the relative risks were 0.45 (95% CI, 0.32 to 0.65) for gonorrhea, 0.12 (95% CI, 0.05 to 0.25) for chlamydia, and 0.13 (95% CI, 0.03 to 0.59) for syphilis, and in the PLWH cohort, the relative risks were 0.43 (95% CI, 0.26 to 0.71), 0.26 (95% CI, 0.12 to 0.57), and 0.23 (95% CI, 0.04 to 1.29), respectively. Five grade 3 adverse events and no serious adverse events were attributed to doxycycline. Of the participants with gonorrhea culture available, tetracycline-resistant gonorrhea occurred in 5 of 13 in the doxycycline groups and 2 of 16 in the standard-care groups. CONCLUSIONS: The combined incidence of gonorrhea, chlamydia, and syphilis was lower by two thirds with doxycycline postexposure prophylaxis than with standard care, a finding that supports its use among MSM with recent bacterial STIs. (Funded by the National Institutes of Health; DoxyPEP ClinicalTrials.gov number, NCT03980223.).

Treponema pallidum Periplasmic and Membrane Proteins Are Recognized by Circulating and Skin CD4+ T Cells.

BACKGROUND: Histologic and serologic studies suggest the induction of local and systemic Treponema pallidum-specific CD4+ T-cell responses to T. pallidum infection. We hypothesized that T. pallidum-specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment. METHODS: Peripheral blood mononuclear cells collected from 67 participants were screened by interferon-γ (IFN-γ) ELISPOT response to T. pallidum sonicate. T. pallidum-reactive T-cell lines from blood and skin were probed for responses to 89 recombinant T. pallidum antigens. Peptide epitopes and HLA class II restriction were defined for selected antigens. RESULTS: We detected CD4+ T-cell responses to T. pallidum sonicate ex vivo. Using T. pallidum-reactive T-cell lines we observed recognition of 14 discrete proteins, 13 of which localize to bacterial membranes or the periplasmic space. After therapy, T. pallidum-specific T cells persisted for at least 6 months in skin and 10 years in blood. CONCLUSIONS: T. pallidum infection elicits an antigen-specific CD4+ T-cell response in blood and skin. T. pallidum-specific CD4+ T cells persist as memory in both compartments long after curative therapy. The T. pallidum antigenic targets we identified may be high-priority vaccine candidates.

Evidence-Informed Provision of Doxycycline Post-Exposure Prophylaxis for Prevention of Bacterial Sexually Transmitted Infections.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces the risk of bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women. In the United States, doxy-PEP is in an early stage of integration into clinical practice, and national guidelines for its use were recently released. The goal of this manuscript is to provide practical guidance for clinicians who are considering or currently prescribing doxy-PEP. We address five clinical questions using post hoc analyses of data from the DoxyPEP randomized controlled trial and discuss the potential implications and limitations of each question with the goal of informing clinical practice and implementation of doxy-PEP programs. The questions address patient eligibility criteria for doxy-PEP, the expected benefit and associated doxy-PEP doses for the average patient, the initial number of doses prescribed, and laboratory monitoring of persons taking doxy-PEP.

Clinical Diagnosis Is Highly Predictive of Laboratory-Confirmed Mpox in a Sexual Health Clinic.

BACKGROUND: Promptly recognizing mpox can facilitate earlier diagnosis and appropriate treatment. How accurately clinicians can diagnose mpox based on clinical data and before receiving molecular test results is not known. METHODS: Leveraging public health and clinical data collected in Seattle-King County's Sexual Health Clinic (SHC) from July 29, 2022, to September 30, 2022, we analyzed the proportion of patients who received presumptive versus results-based tecovirimat when clinicians had a high, intermediate, or low suspicion for mpox after clinical evaluation. We calculated the sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) of this approach against criterion standard mpox polymerase chain reaction (PCR) results. RESULTS: Of 321 patients evaluated for mpox in the SHC, median age was 34.5 years and 88% were cisgender men. Overall, 121 of 319 (38%) tested positive by mpox PCR. Clinicians had high suspicion for mpox in 122 patients and offered empiric tecovirimat to 92 (88%), of whom 85 (92%) tested PCR positive. Of 13 intermediate suspicion patients offered presumptive therapy, all accepted but none tested positive by PCR. The sensitivity, specificity, PPV, and NPV of high/intermediate clinical suspicion for mpox were 99%, 90%, 86%, and 99%, respectively. A higher proportion of people with HIV were diagnosed with mpox (57% vs. 36%, P = 0.01, χ2 test), and sensitivity and PPV of high/intermediate clinical suspicion in this subgroup were 100% and 86%, respectively. CONCLUSIONS: Clinical providers working in a high-volume, public SHC were able to both accurately identify and rule out mpox based on clinical examination before receiving PCR test results.

Trends in Chlamydia trachomatis Treatment Prescribing Practices in King County, Washington, 2010-2018.

BACKGROUND: In 2021, national Chlamydia trachomatis (CT) treatment guidelines changed from recommending either azithromycin (1 g; single dose) or doxycycline (100 mg twice daily for 7 days) to recommending only doxycycline as first-line treatment. The distribution and trends in CT prescribing practices before the guidelines change is largely unknown. METHODS: We conducted a trends analysis using Washington STD surveillance data. We included all female cases of urogenital CT 15 years or older who resided in King County and were diagnosed between 2010 and 2018. Surveillance data included information on demographics, sexual history, clinical features, diagnosing facility (eg, emergency department, family planning), and treatment regimen. We conducted descriptive analyses to examine trends in prescribing practices over time and by facility type. We used Poisson regression to examine the association between CT case characteristics and receipt of receipt of azithromycin. RESULTS: There were 36,830 cases of female urogenital CT during the study period. The percent of cases receiving azithromycin increased significantly from 86% in 2010 to 94% in 2018; the percent receiving doxycycline decreased from 13% to 5%. Five of the 8 facility types prescribed azithromycin to >95% of CT cases by 2018. Cases who were younger or cases of color were more likely to receive azithromycin (versus doxycycline) compared with older and White cases, respectively. CONCLUSIONS: A substantial shift in CT prescribing practices will be needed to adhere to new CT treatment guidelines. Our findings highlight the need for targeted provider education and training to encourage the transition to doxycycline use.

Estimating the Proportion of People Living With HIV Who May Benefit From the Reverse Algorithm for the Diagnosis of Incident Syphilis.

ABSTRACT: Among 8455 people engaged in HIV care in 4 US cities, 4925 (58%) had treponemal testing at care entry. Of the 4925 tested, 3795 (77%) had a nonreactive result and might benefit from the reverse algorithm for a future incident syphilis diagnosis. Furthermore, low-barrier treponemal testing as a first step in the reverse algorithm may increase syphilis screening and decrease time to treatment.

Impact of Text-Based Monthly Check-Ins on Pre-Exposure Prophylaxis Retention at a Sexual Health Clinic.

ABSTRACT: We conducted a retrospective cohort study of preexposure prophylaxis patients at the municipal Sexual Health Clinic in Seattle-King County, Washington from 2019 to 2021 to determine whether monthly check-in text messages impacted 4- and 6-month pre-exposure prophylaxis retention. Monthly check-ins did not appear to improve retention above and beyond open-ended texting and appointment reminders.

Sexually Transmitted Infection Partner Services Outcomes Before and During the SARS-CoV-2 Pandemic in King County, WA.

BACKGROUND: SARS-CoV-2 pandemic mitigation efforts resulted in reallocation of public health personnel, likely impacting provision of timely sexually transmitted infection partner services (PS). We describe PS outcomes before and during the pandemic in King County, WA. METHODS: We examined PS outcomes for syphilis and gonorrhea cases diagnosed in 2019 and 3 periods in 2020 (pre-lockdown: January 1, 2020-March 23, 2020; lockdown: March 24, 2020-June 5, 2020; post-lockdown: June 6, 2020-December 31, 2020). We described changes over time in 3 PS outcomes: cases initiated, interviewed, and with named sex partners. We calculated adjusted prevalence ratios (aPRs) with Poisson regression comparing these outcomes in the 2020 periods with 2019. RESULTS: Reported gonorrhea (4611 vs. 4179) and syphilis (665 vs. 586) cases declined from 2019 to 2020. In 2019, 60.7% of cases were initiated, compared with 42.1% before lockdown (aPR, 0.74; 95% confidence interval [CI], 0.70%-0.78%), 41.7% during lockdown (aPR, 0.79; 95% CI, 0.73-0.85), and 41.7% after lockdown (aPR, 0.81; 95% CI, 0.77-0.85). Among initiated cases, the proportion interviewed also seemed to drop in the 3 lockdown periods (52.4%, 41.0%, 44.1%) compared with 2019 (55.7%). However, in adjusted analyses, the prevalence of interview among case patients was only lower pre-lockdown (aPR, 0.91; 95% CI, 0.85-0.99), and higher during (aPR, 1.10; 95% CI, 1.01-1.20) and after (aPR, 1.12; 95% CI, 1.06-1.19). Interviewed patients named partners more often during (21.4%; aPR, 1.35; 95% CI, 1.05-1.74) and less often after lockdown (16.0%; aPR, 0.63; 95% CI, 0.51-0.79), compared with 2019 (26.6%). CONCLUSIONS: These results underscore the need for a trained public health worker reserve, and plans for deployment of existing workers and prioritization of cases to continue essential sexually transmitted infection public health activities during public health crises.

Asymptomatic and Subclinical Mpox: An Association With Modified Vaccinia Ankara Vaccine.

BACKGROUND: How often mpox causes asymptomatic infections, particularly among persons who have received the Modified Vaccinia Ankara (MVA) vaccine, is unknown. METHODS: We performed mpox polymerase chain reaction testing on rectal and pharyngeal specimens collected from symptomatic and asymptomatic patients at a sexual health clinic in Seattle, WA, between May 2022 and May 2023. Analyses evaluated the prevalence of asymptomatic or subclinical infection and, among persons with polymerase chain reaction-positive tests, the association of MVA vaccination status with the symptomatic infection. RESULTS: The study population included 1663 persons tested for mpox during 2353 clinic visits. Ninety-three percent of study participants were cisgender men and 96% were men who have sex with men. A total of 198 symptomatic patients (30%) had a first mpox-positive test during 664 visits. Eighteen patients (1.1%) tested during 1689 visits had asymptomatic or subclinical mpox based on a positive rectal or pharyngeal test done in the absence of testing done because of clinical suspicion for mpox. Fourteen (78%) of 18 persons with asymptomatic/subclinical mpox and 53 (26%) of 198 persons with symptomatic mpox had received at least 1 dose of the MVA vaccine ( P < 0.0001). Controlling for calendar month, study subjects who received 1 and 2 doses of MVA vaccine were 4.4 (95% confidence interval, 1.3-15) and 11.9 (3.6-40) times more likely to have asymptomatic versus symptomatic mpox, respectively, than persons who were unvaccinated. CONCLUSIONS: Asymptomatic mpox is uncommon. Modified Vaccinia Ankara vaccination is associated with an asymptomatic/subclinical infection among persons with mpox.

The Sexual Health Clinic Role in Vaccine and Treatment Access During the 2022 Mpox Outbreak in King County, Washington.

BACKGROUND: Sexual health clinics were frontline providers in the 2022 US mpox public health response, though data on clinic-based mpox vaccine scale-up, diagnoses, and treatment are limited. We describe the role of a public health sexual health clinic (SHC) in King County's mpox response, between 5/23/22-10/31/22. METHODS: In July 2022, the SHC implemented a dedicated vaccine clinic and presumptive tecovirimat treatment (prior to laboratory confirmation) with on-site dispensation. We describe SHC's vaccine scale-up and contribution to clinical care by calculating the weekly number of vaccines administered by SHC and the total number of patients diagnosed and treated for mpox within SHC, and comparing to countywide data. We calculated time from symptom onset to testing and time from testing to treatment, and assessed temporal changes in these metrics using linear regression. RESULTS: The SHC provided ≥1 vaccine doses to 7,442 individuals (10,295 doses), administering 42% of the 24,409 vaccine doses provided countywide, with the greatest contribution in the first week of August (n = 1,562, 58% of countywide vaccinations that week). Of 598 patients evaluated for mpox and tested, 178 (30%) tested positive (37% of countywide cases), and 152 (85% of SHC patients with mpox) received tecovirimat (46% of treatment countywide). Median time from symptom onset to testing decreased from 12 to 6 days (p = 0.045); time from testing to treatment decreased from 4.5 days to 0 days (p < 0.001). CONCLUSION: The SHC was central to mpox vaccination and treatment scale-up, particularly in the first months of the 2022 epidemic.

"Another tool for the sexual health toolkit": U.S. health care provider knowledge and attitudes about doxycycline post-exposure prophylaxis (doxy-PEP) to prevent bacterial sexually transmitted infections among men who have sex with men.

BACKGROUND: Doxycycline post-exposure prophylaxis (doxy-PEP) reduces chlamydia, gonorrhea, and syphilis infections among men who have sex with men (MSM) and transwomen (TW). Perspectives of health care providers (HCPs) regarding doxy-PEP can inform implementation efforts. METHODS: From August 2022 to January 2023, HCPs were recruited from 13 cities with high sexually transmitted infection (STI) rates for semi-structured, in-depth interviews about their awareness of and attitudes towards doxy-PEP for STI prevention. HCPs were purposively sampled to include people with experience prescribing PrEP and provision of care to MSM. Interviews were conducted virtually via Zoom. Transcripts and debrief reports were analyzed using a directed content analysis approach to explore knowledge, attitudes, and beliefs about doxy-PEP. RESULTS: Among 30 HCPs, almost half (47%) were between 31-40 years of age, 53% identified as male, and 47% reported their sexual orientation as gay or queer. Half (53%) of participants practiced in the South, 43% had >100 MSM in their clinic panel, and 17% had previously prescribed doxy-PEP. We identified four overarching themes: 1) HCPs expressed positive attitudes towards doxy-PEP; 2) antimicrobial resistance concerns limit enthusiasm for some HCPs; 3) additional data about the long-term safety of doxy-PEP would improve their confidence; and 4) development of guidelines would facilitate the prescription of doxy-PEP, including eligibility, dosing instructions, and treatment management. CONCLUSION: HCPs were motivated to prescribe doxy-PEP with almost 20% already having prescribed it. Guidelines and data about long-term safety, especially antimicrobial resistance, would facilitate introduction of doxy-PEP into clinical practice.

Associations between adverse childhood experiences, viral suppression, and quality of life among persons living with HIV in Washington state.

Adverse childhood experiences (ACEs) have been linked to numerous negative health outcomes in adulthood and have been recognized as a hurdle to participating in HIV care. However, few studies have examined the cumulative impact that different types of childhood trauma have on HIV care engagement and HIV outcomes. This study characterized the relationship between ACEs, viral suppression, and health-related quality of life (HRQOL) among persons living with HIV (PLWH). We used HIV surveillance data and self-reported information on ACEs and HRQOL from PLWH in Washington State from 2018-2020. Logistic regression was used to assess the relationship between the quantity and type of ACEs and viral suppression. We used Poisson regression to examine the relationship between ACEs and HRQOL as measured by unhealthy days. The majority of PLWH experienced ≥1 ACE (86.8%). ACEs were not significantly associated with the likelihood of viral suppression (OR ≥4 vs 0 ACEs: 0.49, 95% CI: 0.12-2.09), but ACEs were associated with more unhealthy days experienced in a 30-day period (RR ≥4 vs 0 ACEs: 3.19, 95% CI: 1.59-6.40). These findings provide support that trauma is common among PLWH, and efforts to address the impact of childhood trauma may work to improve quality of life.

Implementation of Low-Barrier Human Immunodeficiency Virus Care: Lessons Learned From the Max Clinic in Seattle.

Low-barrier care (LBC) for people with human immunodeficiency virus (HIV) is a differentiated service delivery strategy to engage people in HIV treatment who are not well-engaged in conventionally organized HIV medical care. The LBC approach is flexible, but experience suggests that the intervention has distinct core components. This review summarizes our experience implementing one model of LBC, the Max Clinic in Seattle; describes the core components of the intervention; and presents a framework for implementing low-barrier HIV care with the goal of providing a practical guide for clinical and public health leaders seeking to implement a new LBC program. A systematic approach to addressing key factors during LBC implementation can support practitioners to design an LBC approach that fits the local context while maintaining essential elements of the intervention.

Trans-inclusive Sexual Health Questionnaire to Improve Human Immunodeficiency Virus/Sexually Transmitted Infection (STI) Care for Transgender Patients: Anatomic Site-Specific STI Prevalence and Screening.

BACKGROUND: In 2018, the municipal Sexual Health Clinic in Seattle, implemented trans-inclusive questions about sexual behavior, anatomy, gender-affirming surgeries, and sexually transmitted infection (STI) symptoms in the clinic's computer-assisted self-interview (CASI) to improve care for transgender and nonbinary (TNB) patients. METHODS: We calculated test positivity, the proportion of TNB patient visits that received testing for human immunodeficiency virus (HIV); syphilis; pharyngeal, rectal, and urogenital gonorrhea (GC); and chlamydia (CT) before (5/2016-12/2018) and after (12/2018-2/2020) implementation of new CASI questions, and the proportion of asymptomatic patients who received anatomic site-specific screening based on reported exposures. RESULTS: There were 434 TNB patients with 489 and 337 clinic visits during each period, respectively. Nonbinary patients assigned male at birth (AMAB) had the highest prevalence of GC (10% pharyngeal, 14% rectal, 12% urogenital). Transgender women, transgender men, and nonbinary people AMAB had a high prevalence of rectal CT (10%, 9%, and 13%, respectively) and syphilis (9%, 5%, and 8%). Asymptomatic transgender women, transgender men, and nonbinary patients AMAB were more likely to receive extragenital GC/CT screening compared with nonbinary patients assigned female at birth. After implementation of trans-inclusive questions, there was a 33% increase in the number of annual TNB patient visits but no statistically significant increase in HIV/STI testing among TNB patients. CONCLUSIONS: TNB people had a high prevalence of extragenital STIs and syphilis. Implementation of trans-inclusive medical history questions at a clinic that serves cisgender and transgender patients was feasible and important for improving the quality of affirming and inclusive sexual healthcare.

Substance Use and Mental Health Comorbidities and Receipt of Specialty Care Among Patients Enrolled in a Low-Barrier HIV Clinic.

Low-barrier care is one model of a differentiated service delivery approach for people with HIV (PWH) who are not engaged in conventionally-organized HIV care. Although psychiatric and substance use disorders are common among patients in low-barrier clinics, approaches to behavioral health service delivery within this context have not been well-described. We conducted a descriptive analysis using retrospective review of medical records to evaluate substance use and psychiatric comorbidities and receipt of behavioral health services among patients in the Max Clinic in Seattle, Washington. Among 227 patients enrolled from 2015 to mid-2020, most had a history of hazardous substance use (85%), a psychiatric diagnosis (69%) or unstable housing (69%) documented in the medical record. Less than half of patients referred for depression treatment (33%) or for opioid use disorder treatment (40%) completed even one specialty care visit. More effective approaches are needed to engage patients in behavioral health services within the context of low-barrier HIV care.

Etiologies of Proctitis at a Sexual Health Clinic in Seattle, Washington From 2011 to 2021.

ABSTRACT: We analyzed microbiologic etiologies of proctitis among patients seen in an urban sexual health clinic during 2011 to 2021. Among 759 cases, 179 (24%) tested positive for Neisseria gonorrhoeae , 171 (23%) for Chlamydia trachomatis , 21 (3%) for herpes simplex virus, 30 (4%) for syphilis, and 73 (10%) for multiple pathogens; no pathogen was identified in 425 (56%).

Characterization of Patients Seeking Care at a Sexual Health Clinic Who Report Engaging in Exchange Sex.

BACKGROUND: People who exchange sex (PWES) for money or drugs are at increased risk for poor health outcomes and may be reluctant to engage in health services. METHODS: We conducted a cross-sectional analysis of patients seen for new problem visits at the Public Health-Seattle and King County Sexual Health Clinic between October 2010 and March 2020 who reported exchanging sex for drugs or money in a computer assisted self-interview. We analyzed demographics; sexually transmitted infections (STIs), human immunodeficiency virus (HIV), and hepatitis C virus (HCV) history; and HIV preexposure prophylaxis (PrEP) use, stratified by gender. We compared characteristics of people who ever versus never exchanged sex using χ 2 tests and analyzed the visit reason and outcomes among PWES. RESULTS: Among 30,327 patients, 1611 (5%) reported ever exchanging sex: 981 (61%) cisgender men, 545 (34%) cisgender women, and 85 (5%) transgender and gender diverse persons. Compared with people who never exchanged sex, PWES were more likely to report homelessness (29% vs 7%, P < 0.001), injection drug use (39% vs 4%, P < 0.001), prior STIs (36% vs 19%, P < 0.001), prior HIV diagnosis (13% vs 5%, P < 0.001), and prior HCV diagnosis (13% vs 2%, P < 0.001). People who exchange sex came to the clinic seeking STI tests (60%), HIV tests (45%), and care for STI symptoms (38%). Overall, 320 (20%) PWES were diagnosed with STIs, 15 (1%) were newly diagnosed with HIV, and 12 (1%) initiated PrEP at the visit. CONCLUSION: People who exchange sex have complex barriers to care, and sexual health clinic visits present an opportunity to improve health services for this population.

Coinfection With Chlamydial and Gonorrheal Infection Among US Adults With Early Syphilis.

ABSTRACT: Among 865 adults with early syphilis considered for a multicenter treatment trial, 234 (27%) were excluded before enrollment because of bacterial sexually transmitted infection coinfection. Coinfection with Neisseria gonorrhoeae (29%), Chlamydia trachomatis (22%), or both (23%) was common. Study findings highlight the need for comprehensive bacterial sexually transmitted infection screening in patients with syphilis.

Chlamydia and Gonorrhea.

Gonorrhea and chlamydia rates have risen to record-high levels in the United States over the past decade. Because these infections are often asymptomatic, effective clinical management relies on screening of asymptomatic patients, particularly women younger than 25 years and men who have sex with men. If undetected and untreated, gonorrhea and chlamydia can lead to infertility, ectopic pregnancy, and chronic pelvic pain and can facilitate HIV acquisition and transmission. Primary care providers need to be aware of recent changes in recommended treatments for both infections.

Doxycycline Versus Azithromycin for the Treatment of Rectal Chlamydia in Men Who Have Sex With Men: A Randomized Controlled Trial.

BACKGROUND: Azithromycin and doxycycline are both recommended treatments for rectal Chlamydia trachomatis (CT) infection, but observational studies suggest that doxycycline may be more effective. METHODS: This randomized, double-blind, placebo-controlled trial compared azithromycin (single 1-g dose) versus doxycycline (100 mg twice daily for 7 days) for the treatment of rectal CT in men who have sex with men (MSM) in Seattle and Boston. Participants were enrolled after a diagnosis of rectal CT in clinical care and underwent repeated collection of rectal swabs for nucleic acid amplification testing (NAAT) at study enrollment and 2 weeks and 4 weeks postenrollment. The primary outcome was microbiologic cure (CT-negative NAAT) at 4 weeks. The complete case (CC) population included participants with a CT-positive NAAT at enrollment and a follow-up NAAT result; the intention-to-treat (ITT) population included all randomized participants. RESULTS: Among 177 participants enrolled, 135 (76%) met CC population criteria for the 4-week follow-up visit. Thirty-three participants (19%) were excluded because the CT NAAT repeated at enrollment was negative. Microbiologic cure was higher with doxycycline than azithromycin in both the CC population (100% [70 of 70] vs 74% [48 of 65]; absolute difference, 26%; 95% confidence interval [CI], 16-36%; P < .001) and the ITT population (91% [80 of 88] vs 71% [63 of 89]; absolute difference, 20%; 95% CI, 9-31%; P < .001). CONCLUSIONS: A 1-week course of doxycycline was significantly more effective than a single dose of azithromycin for the treatment of rectal CT in MSM. CLINICAL TRIALS REGISTRATION: NCT03608774.