Chase A. Cannon

The US government currently spends >$29 billion annually on HIV treatment, but only 69% of people with diagnosed HIV (PWH) in the US are virally suppressed, a failure partially related to poverty. Medical providers preferentially treat HIV using higher cost medications, and use of higher cost drugs for PrEP is increasing. New, long-acting antiretrovirals (ARVs) have the potential to improve prevention and care while further increasing costs. We believe that the US approach to HIV should change to increase the use of lower cost HIV medications and promote the selective use of long-acting ARVs to treat people who cannot achieve viral suppression using oral drugs. A portion of the money saved through more efficient medication utilization management should be used to improve access to care and provide socioeconomic support to low-income PWH. Together, these changes have the potential to decrease costs, improve health outcomes, and better align spending with patient preferences.

Background: Mycoplasma genitalium (MG) can cause nongonococcal urethritis (NGU) and symptomatic proctitis. Rising antimicrobial resistance and lack of clinically available molecular resistance assays make MG treatment challenging. This study adds systematic data on the effectiveness of alternative MG regimens. Methods: Adult natal male patients who attended a public Sexual Health Clinic (SHC) and had ≥2 positive MG nucleic acid amplification tests within any 6-month period from January 2023-September 2025 were included. We classified cases as persistent infection or reinfection using clinical, demographic and self-reported behavioral data. For each patient, we summarized total number of visits, number, duration and components of each antibiotic regimen, and outcomes by MG clinical syndrome and infection status (persistence vs reinfection). Results: Among 3,009 SHC patients, 400 (13%) had incident MG and 19 (4.8%) met inclusion criteria for repeat MG infection across 61 clinic visits. Nongonococcal urethritis (n=14/19 patients, 74%) and proctitis (n=2/19 patients, 10%) were the most prevalent syndromes. Suspected reinfection was common (40%). All 19 patients achieved cure, including 10 (53%) with microbiologic and 9 (47%) with presumed clinical cure, after treatment for a mean of 18-49 days with between 1-9 antibiotic regimens. Eight (53%) patients were cured with doxycycline plus moxifloxacin, two (100%) with doxycycline plus pristinamycin, three (75%) with minocycline alone, and three (75%) with prolonged minocycline plus tinidazole treatment. Conclusions: Despite frequent reinfection, most repeat positive tests represented persistent MG infections. All cases achieved cure after initial treatment failure, but many required multiple regimens over several weeks.

Background: Daily oral pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV but remains underutilized in the United States. Various factors, including limited access, contribute to drop-offs across the PrEP care continuum. In 2021, Seattle-King County’s sexual health clinic (SHC) introduced same-day, in-clinic dispensing of an initial bottle of oral emtricitabine/tenofovir disoproxil fumarate at no out-of-pocket cost as an alternative to electronic prescribing to external community pharmacies (e-prescribing). Methods: We conducted a retrospective observational study using routinely collected SHC data to identify patients who completed ≥1 initial PrEP visit from November 1, 2020, to May 30, 2023. Successful early PrEP retention was defined as an initial visit, a PrEP prescription within 14 days, and a follow-up visit within 6 months. We compared the proportion achieving early retention across three phases: Phase 1 (e-prescribing only), Phase 2 (transition period), and Phase 3 (same-day dispensing with some e-prescribing), using two-sample tests of proportions. Results: Of 917 eligible patients, 649 (70.8%) were successfully retained on PrEP; 25.0% were uninsured. Early retention was similar across phases: 71.9% (210/292) in Phase 1, 70.0% (194/277) in Phase 2, and 70.4% (245/348) in Phase 3. Compared with Phase 1, retention did not differ significantly in Phase 2 ( P=0.62 ) or Phase 3 ( P=0.67 ), nor by dispensing modality within Phases 2 and 3. Conclusions: In this urban SHC, early PrEP retention remained stable at approximately 70%. Same-day, in-clinic dispensing was not associated with improved early retention but may reduce barriers and delays, representing a feasible low-barrier delivery model in resourced SHCs.

SUMMARY: Sexual transmission of enteric infections (STEIs) among men who have sex with men (MSM) has been reported since the 1960s and is increasingly recognized since the widespread adoption of multiplex molecular diagnostics. However, the overall burden of sexually transmitted enteric infections has been difficult to ascertain, as the public health response to these infections and identification of transmission networks fall between the traditional groupings of sexually transmitted and foodborne diseases. The global emergence of extensively drug-resistant Shigella and Campylobacter infections among MSM and the potential for cross-over between different at-risk populations underscores the importance of timely diagnosis, appropriate treatment, and the need to consider community-level education and testing. Moreover, the possible impact of pre- and post-exposure prophylaxis for HIV and sexually transmitted infections on STEI is presently uncertain. This review examines our evolving understanding of STEI, discusses specific pathogens of urgent importance, and prioritizes areas for further study.

Background: Nonbinary/genderqueer (NB/GQ) individuals represent a distinct population with unique sexual health care needs. We characterize trends in clinic attendance, sociodemographics, sexually transmitted infection (STI), and drug use among NB/GQ patients at an urban sexual health clinic (SHC). Methods: We analyzed Public Health, Seattle & King County, Seattle (PHSKC) SHC visit data collected between January 2016 and October 2023. We used the Cochran-Armitage trend test to identify trends in reported gender identity and χ ² tests to identify sociodemographic characteristics associated with cisgender, transgender, and NB/GQ. We evaluated the associations between gender identity and the prevalence of syphilis, urogenital gonorrhea, rectal chlamydia infection, methamphetamine, and nonprescribed injection drug use using generalized estimating equations. Results: Of 82,384 visits, 1672 (2.0%), 867 (1.1%), and 79,845 (96.9%) were NB/GQ, transgender, and cisgender patients, respectively. From 2016 to 2023, the proportion of visits among NB/GQ and transgender patients increased from 0.7% to 3.5% and 0.7% to 1.7%, respectively ( p trendP < 0.001), younger vs older patients (14–25 years: 3.1% vs >46: 0.2%, P < 0.001), and white versus black patients (2.3% vs 1.0%, P < 0.001). Compared with MSM, NB/GQ patients had significantly lower odds of urogenital gonorrhea (adjusted odds ratio [aOR], 0.50; 95% confidence interval [CI], 0.32–0.80). The differences in rectal chlamydia (aOR, 0.78; 95% CI, 0.59–1.02) and syphilis (aOR, 0.96; 95% CI, 0.87–1.06) were not statistically significant. There were no significant differences between the NB/GQ and transgender visits. Conclusions: Gender diversity among SHC attendees increased significantly over the 8 years. Continued monitoring is essential for tailoring STI/HIV prevention strategies.

Background: Doxycycline post-exposure prophylaxis (doxy PEP) is increasingly used among men who have sex with men (MSM). Its impact on antimicrobial resistance and the microbiome is uncertain. Methods: We used Neisseria gonorrhoeae (NG) surveillance data from King County, Washington, USA, and joinpoint regression to investigate trends in NG-tetracycline resistance (tetR), 2017–2024 and, among sexual health clinic (SHC) patients, evaluated the association of NG-tetR with doxy PEP use. We evaluated nasopharyngeal colonization with Staphylococcus aureus and Group A Streptococcus (GAS) in 703 MSM SHC patients, August 2023-July 2024. Results: Among 2312 MSM with NG, tetR was stable 2017 to quarter 1 (Q1) 2023 (mean = 27%) and thereafter rose to 70% in Q2 2024 (P < .0001). (King County released doxy PEP guidelines in Q2 2023.) NG with high-level (HL) tetR increased Q1 2021 to Q2 2024 (2% to 65%) (P < .0001). Taking >3 doses of doxy PEP/month was associated with both tetR and HL tetR (P ≤ .01 for both), though any use of doxy PEP was not associated with tetR or HL tetR. S. aureus colonization was less common among doxy PEP users than non-users (27% vs 36%, P = .02), but colonization with both tetracycline-resistant S. aureus and GAS were more common among doxy PEP users than non-users (18% vs 8%, P < .0001% and 9% vs 4%, P = .008, respectively). Conclusions: TetR in NG rapidly increased from 2021 to 2024, and most NG among King County MSM now have HL tetR. Doxy PEP use is associated with colonization with GAS and tetracycline-resistant S. aureus, suggesting that doxy PEP impacts off-target bacteria.

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.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces bacterial sexually transmitted infections among men who have sex with men and transgender women. Although poised for widespread clinical implementation, the impact of doxy-PEP on antimicrobial resistance remains a primary concern as its effects on the gut microbiome and resistome, or the antimicrobial resistance genes (ARGs) present in the gut microbiome, are unknown. To investigate these effects, we studied participants from the DoxyPEP trial, a randomized clinical trial comparing doxy-PEP use, a one-time doxycycline 200-mg dose taken after condomless sex (DP arm, n = 100), to standard of care (SOC arm, n = 50) among men who have sex with men and transgender women. From self-collected rectal swabs at enrollment (day-0) and after 6 months (month-6), we performed metagenomic DNA sequencing (DNA-seq) or metatranscriptomic RNA sequencing (RNA-seq). DNA-seq data were analyzable from 127 samples derived from 89 participants, and RNA-seq data were analyzable from 86 samples derived from 70 participants. We compared the bacterial microbiome and resistome between the two study arms and over time. The median number of doxycycline doses taken since enrollment by participants with DNA-seq data was zero (interquartile range (IQR): 0–7 doses) for the SOC arm and 42 (IQR: 27–64 doses) for the DP arm. Tetracycline ARGs were detected in all day-0 DNA-seq samples and in 85% of day-0 RNA-seq samples. The proportional mass of tetracycline ARGs in the resistome increased between day-0 and month-6 in DP participants from 46% to 51% in the metagenome (P = 2.3 × 10⁻²) and from 4% to 15% in the metatranscriptome (P = 4.5 × 10⁻⁶), but no statistically significant increases in other ARG classes were observed. Exposure to a higher number of doxycycline doses correlated with proportional enrichment of tetracycline ARGs in the metagenome (Spearman’s ρ = 0.23, P = 9.0 × 10⁻³) and metatranscriptome (Spearman’s ρ = 0.55, P = 3.7 × 10⁻⁸). Bacterial microbiome alpha diversity, beta diversity and total bacterial mass did not differ between day-0 and month-6 samples from DP participants when assessed by either DNA-seq or RNA-seq. In an abundance-based correlation analysis, we observed an increase over time in the strength of the correlation between tetracycline ARGs and specific bacterial taxa, including some common human pathogens. In sum, doxy-PEP use over a 6-month period was associated with an increase in the proportion of tetracycline ARGs comprising the gut resistome and an increase in the expression of tetracycline ARGs. At 6 months of doxy-PEP use, no residual differences were observed in alpha and beta diversity or taxonomic composition of the gut microbiome. As doxy-PEP is implemented as a public health strategy, further studies and population-level surveillance of doxycycline-resistant pathogens are needed to understand the implications of these findings. ClinicalTrials.gov registration number: NCT03980223.

Background: HIV prevention is a public health priority. Despite progress in recent years, pre-exposure prophylaxis (PrEP) use remains suboptimal especially among groups disproportionately impacted by new HIV diagnoses such as gender and sexual minorities of color. Multiple barriers including a lack of PrEP providers and challenges with attending quarterly monitoring visits contribute to low PrEP uptake and retention. Home-based PrEP (HB-PrEP) services could reduce stigma, increase convenience, expand health system capacity for PrEP care, and improve PrEP retention. Objective: Home Option Testing for PrEP (HOT4PrEP) is a hybrid randomized controlled trial (RCT) that aims to examine whether HB-PrEP care is acceptable to PrEP users, feasible to implement in a sexual health clinic setting, and impacts PrEP retention. Methods: The RCT will recruit 458 persons currently taking or soon to initiate PrEP at a sexual health clinic in Seattle, Washington, and randomize them to continue the standard of care or have the option to use HB-PrEP for 2 of 3 triannual PrEP follow-up visits. Participants in the intervention arm will be sent home kits containing gonorrhea and chlamydia swabs and Tasso devices for blood self-collection. The primary outcome is PrEP retention between groups at 20 months; secondary outcomes include user satisfaction and acceptability, feasibility, self-reported PrEP adherence, and sexually transmitted infection (STI) incidence. Interviews with PrEP users and clinic staff will elucidate barriers and facilitators of implementation. Results: The HOT4PrEP RCT began enrolling in March 2022, was on hold during the height of the US mpox epidemic, then resumed enrollment in December 2022. Of the first 100 enrollees, the median age is 34 years, and most are cisgender gay men (89/100, 89%) with at least some college education (91/100, 91%). Among the 49 participants randomized to the HB-PrEP option, 33 (67%) chose to self-collect samples at home at least once, of whom 27 (82%) successfully returned test kits for HIV and STI testing. Primary PrEP retention and qualitative analyses are ongoing. Conclusions: Implementation of HB-PrEP into a high-volume sexual health clinic seems to be feasible and acceptable to early RCT enrollees. This strategy has the potential to address individual and systemic barriers associated with initiating and persisting on PrEP, such as increasing sexual health agency and expanding clinical capacity to serve greater numbers of PrEP users. Trial Registration: ClinicalTrials.gov NCT05856942; https://clinicaltrials.gov/study/NCT05856942 International Registered Report Identifier (IRRID): DERR1-10.2196/56587