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.

A Demedicalized Model to Provide PrEP in a Sexual Health Clinic.

BACKGROUND: Sexual health clinics (SHCs) serve large numbers of patients who might benefit from preexposure prophylaxis (PrEP). Integrating longitudinal PrEP care into SHCs can overburden clinics. We implemented an SHC PrEP program that task shifted most PrEP operations to nonmedical staff, disease intervention specialists (DIS). METHODS: We conducted a retrospective cohort analysis of PrEP patients in an SHC in Seattle, WA, from 2014 to 2020 to assess the number of patients served and factors associated with PrEP discontinuation. Clinicians provide same-day PrEP prescriptions, whereas DIS coordinate the program, act as navigators, and provide most follow-up care. RESULTS: Between 2014 and 2019, 1387 patients attended an initial PrEP visit, 93% of whom were men who have sex with men. The number of patients initiating PrEP per quarter year increased from 20 to 81. The number of PrEP starts doubled when the clinic shifted from PrEP initiation at scheduled visits to initiation integrated into routine walk-in visits. The percentage of visits performed by DIS increased from 3% in 2014 to 45% in 2019. Median duration on PrEP use was 11 months. PrEP discontinuation was associated with non-Hispanic black race/ethnicity [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.02 to 1.76], age <20 years (HR 2.17, 95% CI: 1.26 to 3.75), age between 20 and 29 years (HR 1.55, 95% CI: 1.06 to 2.28), and methamphetamine use (HR 1.98, 95% CI: 1.57 to 2.49). The clinic had 750 patients on PrEP in the final quarter of 2019. CONCLUSIONS: A demedicalized SHC PrEP model that task shifts most operations to DIS can provide PrEP at scale to high priority populations.

Single-Arm Open-Label Clinical Trial of Two Grams of Aztreonam for the Treatment of Neisseria gonorrhoeae.

The threat of ceftriaxone-resistant Neisseria gonorrhoeae necessitates new gonorrhea treatment regimens. Repurposing older antibiotics not routinely used for N. gonorrhoeae may expeditiously identify new therapies. Ideally, all recommended therapies should eradicate gonorrhea at the pharynx. Between April and September 2019, we enrolled men in an open-label, one-arm clinical trial of single-dose intramuscular aztreonam (2 g). Enrollment criterion included (i) nucleic acid amplification test (NAAT)-positive pharyngeal gonorrhea for ≤14 days or (ii) Gram stain-positive gonococcal urethritis plus report of performing oral sex in ≤2 months. At enrollment, we collected cultures from NAAT-positive or screening sites, and men returned 3 to 8 days following treatment for a test of cure (TOC) by culture. The per-protocol analysis required men to be culture positive at enrollment and to return for TOC. We calculated efficacy as the number of subjects with negative culture at TOC divided by the number culture positive at enrollment by anatomic site. Thirty-two men enrolled in the study; 21 were pharyngeal NAAT positive, and 11 had gonococcal urethritis. The per-protocol analysis included 17 men, 6 with pharyngeal, 9 with urethral, and 4 with rectal gonococcal infections. Aztreonam cured 2 of 6 pharyngeal infections (33%; 95% confidence interval [CI], 4.3% to 78%) and 3 of 4 rectal infections (75%; 95% CI, 19% to 99%). All 11 men with urethritis were cured (100%; 95% CI, 66% to 100%). The aztreonam MIC90 was 0.5 µg/ml (range, 0.06 to 2.0 µg/ml). All treatment failures occurred at a MIC of ≥0.25 µg/ml. Single-dose aztreonam is not a reliable treatment for gonorrhea at the pharynx but may be useful for men with gonococcal urethritis and beta-lactam allergy. (This study has been registered at ClinicalTrials.gov under identifier NCT03867734.).

Primary Syphilis in the Male Urethra: A Case Report.

We documented urethral Treponema pallidum infection in a man with nongonococcal urethritis and a negative syphilis serology using broad-range bacterial polymerase chain reaction (PCR) and sequencing, targeted PCR, and immunofluorescence microscopy. He subsequently seroconverted for syphilis. Early syphilis may present as urethritis. Urethral T. pallidum shedding can occur before seroconversion.

Rapid localized spread and immunologic containment define Herpes simplex virus-2 reactivation in the human genital tract.

Herpes simplex virus-2 (HSV-2) is shed episodically, leading to occasional genital ulcers and efficient transmission. The biology explaining highly variable shedding patterns, in an infected person over time, is poorly understood. We sampled the genital tract for HSV DNA at several time intervals and concurrently at multiple sites, and derived a spatial mathematical model to characterize dynamics of HSV-2 reactivation. The model reproduced heterogeneity in shedding episode duration and viral production, and predicted rapid early viral expansion, rapid late decay, and wide spatial dispersion of HSV replication during episodes. In simulations, HSV-2 spread locally within single ulcers to thousands of epithelial cells in <12 hr, but host immune responses eliminated infected cells in <24 hr; secondary ulcers formed following spatial propagation of cell-free HSV-2, allowing for episode prolongation. We conclude that HSV-2 infection is characterized by extremely rapid virological growth and containment at multiple contemporaneous sites within genital epithelium. DOI:http://dx.doi.org/10.7554/eLife.00288.001.

High-dose valacyclovir decreases plasma HIV-1 RNA more than standard-dose acyclovir in persons coinfected with HIV-1 and HSV-2: a randomized crossover trial.

BACKGROUND: Standard doses of herpes simplex virus (HSV) suppressive therapy reduce plasma HIV-1 RNA levels (0.25-0.53 log10 copies per milliliter) among HIV-1/HSV-2 coinfected persons. Postulated mechanisms for this effect include direct inhibition of HIV-1 by acyclovir or indirect reduction by decreasing HSV-associated inflammation. We hypothesized that high-dose valacyclovir would further reduce plasma HIV-1 RNA and that the effect would be mediated by greater suppression of HSV shedding. METHODS: Thirty-four participants with HIV-1 and HSV-2 not on antiretroviral therapy were enrolled into a randomized, open-label crossover trial of valacyclovir 1000 mg twice daily or acyclovir 400 mg twice daily for 12 weeks, followed by a 2-week washout, and then the alternate treatment arm for 12 weeks. HSV DNA was measured from daily self-collected genital swabs for the initial 4 weeks of each arm, and HIV-1 RNA was quantified from weekly plasma samples. RESULTS: Twenty-eight participants provided plasma samples and genital swabs on both acyclovir and valacyclovir. The genital HSV-2 shedding rate was the same on valacyclovir and acyclovir [7.8% vs. 8.2% of days; relative risk: 0.95; 95% confidence interval (CI): 0.66 to 1.37; P = 0.78]. Plasma HIV-1 RNA was 0.27 log10 copies per milliliter lower on valacyclovir compared with acyclovir (95% CI: -0.41 to -0.14 log10 copies per milliliter; P < 0.001); this was unchanged after adjustment for genital HSV-2 shedding. CONCLUSIONS: High-dose valacyclovir reduces plasma HIV-1 RNA levels more than standard-dose acyclovir in HIV-1/HSV-2-seropositive persons not receiving antiretroviral therapy. The incremental reduction in plasma HIV-1 RNA achieved is not mediated by greater genital HSV-2 suppression.