Intra-Anal Imiquimod Cream against Human Papillomavirus Infection in Men Who Have Sex with Men Living with HIV: A Single-Arm, Open-Label Pilot Study.

Men who have sex with men (MSM) living with HIV have a high prevalence and incidence of anal high-risk human papillomavirus (hrHPV) and anal cancer. We conducted an open-label, single-arm pilot study to examine the tolerability of imiquimod cream among MSM aged ≥18 years, living with HIV, who tested positive for anal hrHPV at Melbourne Sexual Health Centre between April 2018 and June 2020. We instructed men to apply 6.25 mg imiquimod intra-anally and peri-anally 3 doses per week for 16 weeks (period 1) and then one dose per week for a further 48 weeks (period 2). Twenty-seven MSM enrolled in period 1 and 24 (86%) applied at least 50% of doses. All men reported adverse events (AEs), including 39.5% grade 1, 39.5% grade 2, and 21% grade 3 AEs on at least one occasion. Eighteen MSM (67%) temporarily stopped using imiquimod during period 1, most commonly due to local AEs (n = 11) such as irritation and itching. Eighteen MSM continued in period 2 and all applied at least 50% of doses with no treatment-limiting AEs reported. Imiquimod 3 doses per week caused local AEs in most men and was not well tolerated. In contrast, once-a-week application was well tolerated over 48-weeks with no treatment-limiting AEs.

Doxycycline and Sitafloxacin Combination Therapy for Treating Highly Resistant Mycoplasma genitalium.

Antimicrobial-resistant Mycoplasma genitalium is becoming increasingly common and creating major treatment challenges. We present early data on combination therapy with doxycycline and sitafloxacin to treat highly resistant M. genitalium. We found the regimen was well tolerated and cured 11/12 infections that had failed prior regimens with moxifloxacin and pristinamycin.

Pooling Pharyngeal, Anorectal, and Urogenital Samples for Screening Asymptomatic Men Who Have Sex with Men for Chlamydia trachomatis and Neisseria gonorrhoeae.

Screening for Chlamydia trachomatis and Neisseria gonorrhoeae at the pharyngeal, urogenital, and anorectal sites is recommended for men who have sex with men (MSM). Combining the three individual-site samples into a single pooled sample could result in significant cost savings, provided there is no significant sensitivity reduction. The aim of this study was to examine the sensitivity of pooled samples for detecting chlamydia and gonorrhea in asymptomatic MSM using a nucleic acid amplification test. Asymptomatic MSM who tested positive for chlamydia or gonorrhoea were invited to participate. Paired samples were obtained from participants prior to administration of treatment. To form the pooled sample, the anorectal swab was agitated in the urine specimen transport tube and then discarded. The pharyngeal swab and 2 ml of urine sample were then added to the tube. The difference in sensitivity between testing of pooled samples and individual-site testing was calculated against an expanded gold standard, where an individual is considered positive if either pooled-sample or individual-site testing returns a positive result. All samples were tested using the Aptima Combo 2 assay. A total of 162 MSM were enrolled in the study. Sensitivities of pooled-sample testing were 86% (94/109; 95% confidence interval [CI], 79 to 92%]) for chlamydia and 91% (73/80; 95% CI, 83 to 96%) for gonorrhea. The sensitivity reduction was significant for chlamydia (P = 0.02) but not for gonorrhea (P = 0.34). Pooling caused 22 infections (15 chlamydia and 7 gonorrhoea) to be missed, and the majority were single-site infections (19/22). Pooling urogenital and extragenital samples from asymptomatic MSM reduced the sensitivity of detection by approximately 10% for chlamydia but not for gonorrhea.

Moxifloxacin and Sitafloxacin Treatment Failure in Mycoplasma genitalium Infection: Association with parC Mutation G248T (S83I) and Concurrent gyrA Mutations.

BACKGROUND: The basis of fluoroquinolone treatment failure for Mycoplasma genitalium is poorly understood. METHODS: To identify mutations associated with failure we sequenced key regions of the M. genitalium parC and gyrA genes for patients undergoing sequential therapy with doxycycline-moxifloxacin (201 patients, including 21 with failure) or doxycycline-sitafloxacin (126 patients, including 13 with failure). RESULTS: The parC G248T/S83I mutation was more common among patients with failed sequential doxycycline-moxifloxacin (present in 76.2% of failures vs 7.8% cures, P < .001) or doxycycline-sitafloxacin (50% vs 16.8%, respectively; P = .01) treatment. Doxycycline-sitafloxacin was more efficacious than doxycycline-moxifloxacin against infections carrying the parC mutation conferring S83I amino acid change. Treatment was more likely to fail in these infections if they had a concurrent gyrA mutation (M95I or D99N) (P = .07 for doxycycline-moxifloxacin group and P = .009 for doxycycline-sitafloxacin group), suggesting an additive effect. CONCLUSIONS: This study indicates that parC G248T/S83I mutations contribute to failure of moxifloxacin and sitafloxacin, and the findings will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials for M. genitalium.

Resistance-Guided Antimicrobial Therapy Using Doxycycline-Moxifloxacin and Doxycycline-2.5 g Azithromycin for the Treatment of Mycoplasma genitalium Infection: Efficacy and Tolerability.

BACKGROUND: Macrolide resistance in Mycoplasma genitalium (MG) exceeds 50% in many regions, and quinolone resistance is increasing. We recently reported that resistance-guided therapy (RGT) using doxycycline followed by sitafloxacin or 2.5 g azithromycin cured 92% and 95% of macrolide-resistant and macrolide-susceptible infections, respectively. We present data on RGT using doxycycline-moxifloxacin, the regimen recommended in international guidelines, and extend data on the efficacy of doxycycline-2.5 g azithromycin and de novo macrolide resistance. METHODS: Patients attending Melbourne Sexual Health Centre between 2017 and 2018 with sexually transmitted infection syndromes were treated with doxycycline for 7 days and recalled if MG-positive. Macrolide-susceptible cases received 2.5 g azithromycin (1 g, then 500 mg daily for 3 days), and resistant cases moxifloxacin (400 mg daily, 7 days). Test of cure was recommended 14-28 days post-antimicrobials. RESULTS: There were 383 patients (81 females/106 heterosexual males/196 men who have sex with men) included. Microbial cure following doxycycline-azithromycin was 95.4% (95% confidence interval [CI], 89.7-98.0) and doxycycline-moxifloxacin was 92.0% (95% CI, 88.1-94.6). De novo macrolide resistance was detected in 4.6% of cases. Combining doxycycline-azithromycin data with our prior RGT study (n = 186) yielded a pooled cure of 95.7% (95% CI, 91.6-97.8). ParC mutations were present in 22% of macrolide-resistant cases. CONCLUSIONS: These findings support the inclusion of moxifloxacin in resistance-guided strategies and extend the evidence for 2.5 g azithromycin and presumptive use of doxycycline. These data provide an evidence base for current UK, Australian, and European guidelines for the treatment of MG.

Increasing proportion of herpes simplex virus type 1 among women and men diagnosed with first-episode anogenital herpes: a retrospective observational study over 14 years in Melbourne, Australia.

OBJECTIVES: Reports of rising herpes simplex virus type 1 (HSV-1) genital infections relative to HSV-2 have been published up to 2006 in Australia. These changes have been attributed to declining childhood immunity to HSV-1. We described the temporal trends of HSV-1 and HSV-2 up to 2017 in Melbourne, Australia, to determine if the earlier trend is continuing. METHODS: We conducted a retrospective review of the medical records of 4517 patients who were diagnosed with first episode of anogenital HSV infection at the Melbourne Sexual Health Centre, Australia, between January 2004 and December 2017. HSV-1 and HSV-2 were calculated as a proportion of all first episode of anogenital HSV infections. The change in the proportions of HSV-1 and HSV-2 over time was assessed by a χ2 trend test. Risk factors associated with HSV-1 were examined using a multivariable logistic regression model. RESULTS: The proportion of first episode of anogenital herpes due to HSV-1 increased significantly over time in women (from 45% to 61%; ptrend<0.001) and heterosexual men (from 38% to 41%; ptrend=0.01) but not in men who have sex with men (MSM) (ptrend=0.21). After adjusting for condom use, partner number and age, the annual increase remained significant only in women (OR 1.08, 95% CI 1.03 to 1.13, p<0.001). In MSM, HSV-1 caused up to two-thirds of anogenital herpes in most years and HSV-1 was more likely to be diagnosed at an anal site than genital site (OR 1.69, 95% CI 1.23 to 2.32, p<0.001). Younger age (<28 years) was an independent risk factor for HSV-1 in all groups. CONCLUSIONS: The proportion of first-episode anogenital herpes due to HSV-1 has been rising in women since 2004. HSV-1 has become the leading cause of anogenital herpes in younger populations, women and MSM.