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BackgroundIn many countries, HIV pre-exposure prophylaxis (PrEP) users are screened quarterly for STIs. We assessed the consequences of less frequent STI testing. We also assessed determinants of asymptomatic STI and potential for onward transmission.MethodsUsing data from the AMPrEP study, we assessed the proportion of syphilis, and genital, anal, and pharyngeal chlamydia and gonorrhoea diagnoses which would have been delayed with biannual versus quarterly screening. We assessed the potential for onward transmission by examining reported condomless anal sex (CAS) in periods after to-be-omitted visits when screening biannually. We assessed determinants of incident asymptomatic STIs using Poisson regression and calculated individual risk scores on the basis of the coefficients from this model.ResultsWe included 366 participants. Median follow-up was 47 months (IQR 43–50). 1,183STIs were diagnosed, of which 932(79%) asymptomatic. With biannual screening, 483 asymptomatic STIs (52%) diagnoses would have been delayed at 364 study visits. Of these visits, 129 (35%), 240 (66%) and 265 (73%) were followed by periods of CAS with steady, known casual or unknown casual partners, respectively. Older participants had a lower risk of asymptomatic STI (incidence rate ratio (IRR) 0.86/10-year increase, 95% CI 0.80 to 0.92), while CAS with known (IRR 1.36, 95% CI 1.10 to 1.68) and unknown (IRR 1.86, 95% CI 1.48 to 2.34) casual partners and chemsex (IRR 1.51, 95% CI 1.28 to 1.78) increased the risk. The individual risk scores had limited predictive value (sensitivity=0.70 (95% CI 0.66 to 0.74), specificity=0.50 (95% CI 0.48 to 0.51)).ConclusionReducing the STI screening frequency to biannually among PrEP users will likely result in delayed diagnoses, potentially driving onward transmission. Although determinants for asymptomatic STIs were identified, predictive power was low.

IntroductionEvent-driven pre-exposure prophylaxis (edPrEP) with oral tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective for preventing HIV acquisition in men who have sex with men (MSM) and is preferred over daily PrEP by some MSM. However, it is largely unknown how well MSM adhere to edPrEP. We then aimed to assess PrEP protection during CAS among MSM using edPrEP and participating in the Amsterdam PrEP demonstration project (AMPrEP).MethodsWe analysed data from participants enrolled in AMPrEP who were taking edPrEP. We measured adherence through (1) a mobile application in which sexual behaviour and PrEP-use were recorded daily, (2) three-monthly self-completed questionnaires and (3) dried blood spot (DBS) samples collected around six, twelve and twenty-four months after PrEP initiation. We assessed the proportion of days with condomless anal sex (CAS) acts that were protected by PrEP, per partner type (i.e. steady partners, known casual partners, unknown casual partners), and the proportion of three-month periods during which PrEP was correctly used. Intracellular TFV-diphosphate (TFV-DP) concentrations were determined from DBS. Good adherence was defined as at least one tablet before and one tablet within 48 hours after a CAS act.ResultsBetween 11 September 2015 and 6 October 2019, 182 of 376 MSM (48.4%) used edPrEP for at least one three-month period. Of the 8224 CAS days that were reported in the app during edPrEP-use, we observed good protection for most CAS days involving steady partners (n = 1625/2455, 66.9%), known casual partners (n = 3216/3472, 92.6%) and unknown casual partners (n = 2074/2297, 90.3%). Men reported consistently correct PrEP-use in 851 (81.4%) of the 1046 three-month periods of edPrEP-use. The median TFV-DP concentration was 591 fmol/sample (interquartile range = 270 to 896).ConclusionsAdherence to edPrEP was high as determined from the online app and questionnaire. DBS measurements were consistent with two to three tablets per week on average.

Background: Neisseria gonorrhoeae causes gonorrhoea, a common sexually transmitted infection. Emerging strains resistant to first-line ceftriaxone threaten N gonorrhoeae management. Hence, alternative treatments are needed. We aimed to evaluate the efficacy of ertapenem, gentamicin, and fosfomycin as alternative treatments for anogenital N gonorrhoeae. Methods: In a randomised, controlled, double-blind, non-inferiority trial (three experimental groups and one control group) at the Centre for Sexual Health in Amsterdam, Netherlands, we included adults aged 18 years or older, with anorectal or urogenital gonorrhoea. With random permuted blocks, participants were randomly assigned (1:1:1:1) to receive intramuscular 500 mg ceftriaxone (control group), intramuscular 1000 mg ertapenem, intramuscular 5 mg/kg gentamicin (maximum 400 mg), or oral 6 g fosfomycin. The primary outcome was the proportion of participants with a negative nucleic acid amplification test of the predefined primary infected site, 7−14 days after treatment. The primary analysis was per protocol (ie, excluding those lost to follow-up). The modified intention-to-treat analysis included all randomly assigned patients with anogenital gonorrhoea considering those lost-to-follow-up as treatment failure. Non-inferiority was established if the lower Hochberg-corrected 95% CI for difference between the experimental and control groups was greater than −10%. For the analysis of adverse events, we included all participants who received medication. The trial was registered at ClinicalTrials.gov (NCT03294395) and is complete. Findings: Between Sept 18, 2017, and June 5, 2020, from 2160 patients invited to participate, we assigned 346 (16%) participants to receive either ceftriaxone (n=103), ertapenem (n=103), gentamicin (n=102), or fosfomycin (n=38). The fosfomycin group was terminated early after interim analysis revealed less than 60% efficacy. In the primary per-protocol analysis, 93 (100%) of 93 patients in the ceftriaxone group, 86 (99%) of 87 patients in the ertapenem group, 79 (93%) of 85 patients in the gentamicin group, and four (12%) of 33 patients in the fosfomycin group cleared N gonorrhoeae (risk difference vs ceftriaxone −0·01 [95% CI −0·08 to 0·05] for ertapenem and −0·07 [−0·16 to −0·01] for gentamicin). Thus, ertapenem proved non-inferior to ceftriaxone. In mITT analysis, risk differences versus ceftriaxone were −0·08 (−0·17 to 0·003) for ertapenem and −0·11 (−0·21 to −0·04) for gentamicin. We observed a higher proportion of patients with at least one adverse event in the ertapenem group (58 [56%] of 103) and fosfomycin group (36 [95%] of 38) versus the ceftriaxone group (24 [23%] of 103). Interpretation: Single-dose 1000 mg ertapenem is non-inferior to single-dose 500 mg ceftriaxone in gonorrhoea treatment. Yet, 5 mg/kg gentamicin (maximum 400 mg) is not non-inferior to ceftriaxone. Ertapenem is a potential effective alternative for anogenital N gonorrhoeae infections and merits evaluation for ceftriaxone-resistant infections. Funding: ZonMw and GGD-Amsterdam. Translation: For the Dutch translation of the abstract see Supplementary Materials section.

Objective: To explore the frequency of and reasons for using condoms among men who have sex with men (MSM) on preexposure prophylaxis (PrEP).Design: We analyzed quantitative app-based diary data on daily sexual practices (August 2015–February 2019) and qualitative in-depth interviews among MSM using daily PrEP and event-driven PrEP (edPrEP) in the Amsterdam PrEP demonstration project.Methods: Participants could report daily about sex acts, PrEP use and condom use per partner type (steady and casual partners). We examined four strategies of PrEP and condom use: PrEP only, PrEP and condoms, condoms only, and neither strategy. We compared the proportions of sex acts per strategy between PrEP regimens. In 43 in-depth interviews, we explored motives for implementing each strategy.Results: Three hundred and fifty-two participants reported 48 949 anal sex acts. PrEP only was the most common strategy employed with any partner type (81%, n = 39 650/48 949) and was motivated by anticipating more pleasurable sex, sexually transmitted infection's perceived curability, and habituation to condomless sex. Combining PrEP and condoms was more often chosen for sex acts with casual partners (18%, n = 6829/37 317) than with steady partners (5%, n = 614/11 632) and was linked to, for example, higher perceived vulnerability for sexually transmitted infections or HIV and avoidance of PrEP disclosure. Condoms only was uncommon but occurred particularly among edPrEP users (4%, n = 379/8695). Applying neither strategy was common among edPrEP users with steady partners (25%, n = 538/2122) and was motivated by low perceived HIV risk.Conclusion: Condoms remain a viable option for PrEP users in certain settings. Condoms were applied in higher risk settings, to avoid PrEP disclosure, or as substitute for PrEP, especially among edPrEP users.

INTRODUCTION: As the incidence of hepatitis C virus (HCV) infections remains high among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) an HCV testing strategy was introduced at the sexually transmitted infections (STI) clinic in Amsterdam in 2017. We aimed to evaluate this HCV testing strategy. METHODS: The HIV-positive MSM and transgender women (TGW) were eligible for HCV testing (anti-HCV and HCV ribonucleic acid) at the STI clinic if they did not visit their HIV clinician in the 3 months before the consultation and had not been tested for HCV at the STI clinic in the previous 6 months. All eligible individuals were administered the 6 questions on risk behavior of the HCV-MSM observational study of acute infection with hepatitis C (MOSAIC) risk score; a risk score of 2 or greater made a person eligible for testing. RESULTS: From February 2017 through June 2018, 1015 HIV-positive MSM and TGW were eligible for HCV testing in 1295 consultations. Eleven active HCV infections (HCV ribonucleic acid positive) were newly diagnosed (positivity rate, 0.9%; 95% confidence interval [CI], 0.4-1.5%). Sensitivity and specificity of the HCV-MOSAIC score for newly diagnosed active HCV infections were 80.0% (95% CI, 49.0-94.3%) and 53.7% (95% CI, 50.8-56.5%), respectively. If an HCV-MOSAIC score of 2 or greater were used to determine whom to test, 46.6% of individuals currently tested for HCV would be eligible for testing. CONCLUSIONS: Using the new HCV testing strategy, HCV testing was done in 1295 consultations with HIV-positive MSM and TGW in 17 months. We newly diagnosed 11 active HCV infections. The HCV-MOSAIC risk score could reduce the number of tests needed, but some active HCV infections will be missed.

IntroductionDaily and event-driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event-driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence.MethodsWe analysed pooled data from two prospective cohort studies among MSM: Be-PrEP-ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three-monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018.Results and discussionWe included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94).ConclusionsA quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered.

Objective Anal cancer precursor lesions high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent among HIV+ men-who-have-sex-with-men (MSM). Treatment of HGAIN is frustrated by high recurrence rates. We investigated the efficacy of the quadrivalent human papillomavirus (qHPV) vaccine as post-treatment adjuvant in preventing HGAIN recurrence in HIV+MSM. Design Randomised, double-blind, placebo-controlled, multicentre trial. Setting Three HIV outpatient clinics in Amsterdam, the Netherlands. Subjects HIV+MSM with CD4 count >350 cells/μl, biopsy-proven intra-anal HGAIN successfully treated in the past year, and lesions still in remission at enrolment, as assessed by high-resolution anoscopy (HRA). Intervention Participants were randomised to three doses of qHPV (Gardasil-4®, MSD) or placebo with vaccinations at 0, 2, and 6 months. HRA was repeated at 6, 12 and 18 months. Main outcome measure The primary outcome was cumulative, biopsy-proven HGAIN recurrence rate at 18 months, evaluated in an intention-to-treat (received all vaccinations) and per-protocol analysis (all vaccinations and complete follow-up). Results We randomised 126 participants of which 64 (50.8%) received qHPV and 62 (49.2%) placebo. All participants received three vaccinations and in both groups for two participants follow-up was incomplete. We found no difference (p = 0·38) in cumulative HGAIN recurrence rates between the qHPV (44/64, 68.8%) and placebo group (38/62, 61.3%) in the intention-to-treat analysis (absolute risk reduction -7.5 (95%CI -24.1-9.2)). This was similar in the per-protocol analysis. Conclusions Despite adequate serological responses to qHPV vaccination, short-term recurrence of HGAIN was not prevented. These findings do not support qHPV vaccination as a treatment adjuvant to prevent HGAIN recurrence in HIV+MSM.

Objective Young women in South Africa are highly affected by sexually transmitted infections (STI), like C. trachomatis (CT) and N. gonorrhoeae (NG). We aimed to estimate the incidence of CT and NG, and its determinants, among young women from the Western Cape, South Africa, participating in an HPV vaccine trial (the EVRI study). Methods HIV-negative women aged 16–24 years were enrolled between October 2012 and July 2013. At enrolment and month 6 participants were screened for CT and NG (Anyplex CT/NG real-time detection method). A questionnaire on demographic and sexual history characteristics was completed at enrolment and month 7. Treatment for CT and/or NG was offered to infected participants. Incidence rates (IR) of CT and NG were estimated. Determinants of incident CT and NG infections were assessed using Poisson regression. Results 365 women were tested for CT and/or NG at least twice. Prevalence of CT and NG at baseline was 33.7% and 10.4%, respectively. Prevalence of co-infection with CT and NG was 7.1%. During 113.3 person-years (py), 48 incident CT infections were diagnosed (IR = 42.4 per 100 py, 95% confidence interval (CI) 31.9–56.2). Twenty-nine incident NG were diagnosed during 139.3 py (IR = 20.8 per 100 py, 95%CI 14.5–29.9). Prevalent CT infection at baseline was associated with incident CT (adjusted incidence rate ratio (aIRR) 5.8, 95%CI 3.0–11.23. More than three lifetime sex partners increased the risk for incident NG (3–4 partners aIRR = 7.3, 95%CI 2.1–26.0; ≥5 partners aIRR = 4.3, 95%CI 1.1–17.5). Conclusions The IR of bacterial STIs among young women in the Western Cape is very high. Besides being previously infected and a higher lifetime number of sex partners, no other risk factors were found for CT and NG, suggesting that the majority of these women were at risk. This indicates the need for intensified prevention of STIs as well as screening and treatment programs to increase sexual health in this region.

Supplemental Digital Content is Available in the Text., Background: We assessed how the Dutch restrictions imposed on March 15, 2020, affected sexual behavior, preexposure prophylaxis (PrEP), and condom use among PrEP users in Amsterdam. Methods: We used data on (1) PrEP use, (2) anal sex acts, and (3) condom use, per partner type [steady partners (SPs), known casual partners (KCPs), and unknown casual partners (UCPs)], collected daily through a mobile application used between December 1, 2019, and June 30, 2020. We compared the period before versus after March 15, 2020, regarding average proportion of days per week at which each end point was reported and average proportion of anal sex acts covered by PrEP and/or condoms. Results: We included data from 136 men who have sex with men. After March 15, 2020, the proportion of days with anal sex increased with SPs [odds ratio (OR) = 1.26; 95% confidence interval (CI) = 1.10 to 1.44) and decreased with KCPs (OR = 0.73; 95% CI = 0.64 to 0.82) and UCPs (OR = 0.54; 95% CI = 0.48 to 0.61). Shifts in partner types were most profound immediately after March 15, 2020, whereas returning to prerestriction levels mid-May 2020. The proportion of days with PrEP use decreased from 74% before to 58% after March 15, 2020 (P < 0.001). After March 15, 2020, PrEP use during sex decreased with UCPs (β = −0.36; 95% CI = −0.72 to 0.00) but not with SPs and KCPs. Condom use during sex decreased with KCPs (β = −0.36; 95% CI = −0.67 to 0.04) and UCPs (β = −0.24; 95% CI = −0.46 to 0.03) but not with SPs. Conclusions: MSM decreased sex with casual partners and increased sex with SP, but changes were transient. Decreases in sex acts with casual partners paralleled decreases in PrEP use. However, condom use during sex with casual partners decreased, indicating the importance of continued sexual health services, including sexually transmitted infections screening and PrEP care, during COVID-19 restrictions.

BackgroundHuman immunodeficiency virus (HIV)–positive men who have sex with men (MSM) are at risk of anal squamous cell carcinoma. Data are limited on the natural history of the precursor to this carcinoma, anal squamous intraepithelial lesions (SILs).MethodsHIV-positive MSM were screened for histopathological SILs by means of high-resolution anoscopy (HRA). For participants without SILs at baseline, we estimated the cumulative incidence and risk factors for SILs. For those with low-grade SILs (LSILs) at baseline, the risk of progression to high-grade SILs (HSILs) and the clearance rate were estimated at the lesion level.ResultsOf 807 men without SILs at baseline, 107 underwent follow-up HRA between 1 to 4.5 years later. At the second visit 18 men (16.8%) showed LSIL, and 25 (23.4%) HSIL. Age was associated with incident LSILs (adjusted odds ratio [aOR], 2.10 per 10-year increase in age; P = .01). Of 393 men with LSILs at baseline, 114 underwent follow-up HRA 0.5 to 2.5 years later. Of the 177 LSILs found at baseline, 87 (49.2%) had cleared at the second visit, and 29 (16.4%) had progressed to HSILs.ConclusionIncident LSILs and HSILs were common during follow-up among HIV-positive MSM without dysplasia at baseline. Among men with LSILs at baseline, nearly half of these lesions cleared, and a small portion progressed.

Background: Some studies on human papillomavirus (HPV) provide not only type-specific incidence rates (IR), but also IRs of HPV groupings (e.g. the nonavalent grouping). We made an inventory of the different approaches used to calculate such IRs and assessed their impact on the estimated IRs of HPV groupings. Methods: We performed a systematic review assessing all approaches used in literature to estimate IRs. Subsequently we applied these approaches to data of a Dutch cohort study on HPV in men who have sex with men (H2M). IRs were estimated for six different HPV groupings. Results: The systematic review yielded six different approaches (A-F) for estimating the IRs, varying in exclusion criteria at baseline, and the definitions of an incident event and person-time. Applying these approaches to the H2M dataset (n = 749), we found differences in the number of participants at risk, number of incidents events, person-time, and IR. For example, for the nonavalent grouping, depending on the approach chosen, the IR varied between 3.09 and 6.54 per 100 person-months. Conclusion: In published studies different epidemiological assumptions are used to estimate IRs of grouped HPV types, leading to widely differing estimates of IRs. IRs between different studies may therefore not be comparable. Keywords: Human papillomavirus, HPV, Incidence rate, Epidemiology