Sexual behaviour and incidence of sexually transmitted infections among men who have sex with men (MSM) using daily and event-driven pre-exposure prophylaxis (PrEP): Four-year follow-up of the Amsterdam PrEP (AMPrEP) demonstration project cohort.

BACKGROUND: An increasing number of countries are currently implementing or scaling-up HIV pre-exposure prophylaxis (PrEP) care. With the introduction of PrEP, there was apprehension that condom use would decline and sexually transmitted infections (STIs) would increase. To inform sexual health counselling and STI screening programmes, we aimed to study sexual behaviour and STI incidence among men who have sex with men (MSM) and transgender women who use long-term daily or event-driven PrEP. METHODS AND FINDINGS: The Amsterdam PrEP demonstration project (AMPrEP) was a prospective, closed cohort study, providing oral daily PrEP and event-driven PrEP to MSM and transgender women from 2015 to 2020. Participants could choose their PrEP regimen and could switch at each three-monthly visit. STI testing occurred at and, upon request, in-between 3-monthly study visits. We assessed changes in numbers of sex partners and condomless anal sex (CAS) acts with casual partners over time using negative binomial regression, adjusted for age. We assessed HIV incidence and changes in incidence rates (IRs) of any STI (i.e., chlamydia, gonorrhoea, or infectious syphilis) and individual STIs over time using Poisson regression, adjusted for age and testing frequency. A total of 367 participants (365 MSM) commenced PrEP and were followed for a median 3.9 years (interquartile range [IQR] = 3.4-4.0). Median age was 40 years (IQR = 32-48), 315 participants (85.8%) self-declared ethnicity as white and 280 (76.3%) had a university or university of applied sciences degree. Overall median number of sex partners (past 3 months) was 13 (IQR = 6-26) and decreased per additional year on PrEP (adjusted rate ratio [aRR] = 0.86/year, 95% confidence interval [CI] = 0.83-0.88). Overall median number of CAS acts with casual partners (past 3 months) was 10 (IQR = 3-20.5) and also decreased (aRR = 0.92/year, 95% CI = 0.88-0.97). We diagnosed any STI in 1,092 consultations during 1,258 person years, resulting in an IR of 87/100 person years (95% CI = 82-92). IRs of any STI did not increase over time for daily PrEP or event-driven PrEP users. Two daily PrEP users, and no event-driven PrEP users, were diagnosed with HIV during their first year on PrEP. Study limitations include censoring follow-up due to COVID-19 measures and an underrepresentation of younger, non-white, practically educated, and transgender individuals. CONCLUSIONS: In this prospective cohort with a comparatively long follow-up period of 4 years, we observed very low HIV incidence and decreases in the numbers of casual sex partners and CAS acts over time. Although the STI incidence was high, it did not increase over time. TRIAL REGISTRATION: The study was registered at the Netherlands Trial Register (NL5413) https://www.onderzoekmetmensen.nl/en/trial/22706.

Concordance between daily diary reported PrEP intake and intraerythrocytic tenofovir diphosphate (TFV-DP) in the Amsterdam PrEP demonstration project.

OBJECTIVE: We assessed the association and concordance between self-reported oral preexposure prophylaxis (PrEP) intake in a diary app and intraerythrocytic drug metabolite concentrations. DESIGN: AMPrEP was a prospective demonstration study providing daily and event-driven PrEP to MSM in Amsterdam, the Netherlands (2015-2020). METHODS: Participants could record their PrEP intake in a diary app. Dried blood spots (DBS) were taken at 6, 12, 24, and 48 months and analysed for tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentrations. We included TFV-DP measurements preceded by diary completion on at least 90% of days in the 6 weeks prior. We examined the association between self-reported PrEP intake (i.e. number of pills) and TFV-DP concentrations using tobit regression with a random intercept per participant. We also calculated concordance between categorized PrEP intake (i.e. <2, 2-3, 4-6 or 7 pills per week) and categorized TFV-DP concentrations (i.e. <350, 350-699,700-1249 or ≥1250 fmol/punch) using weighted Cohen's kappa. Last, we calculated concordance between self-reported recent PrEP intake (yes/no, in past 2 days) and quantifiability of FTC-TP (yes/no) using Cohen's kappa. RESULTS: Seven hundred and fifty-nine DBS measurements from 282 MSM were included. Self-reported PrEP intake was strongly and positively associated with TFV-DP concentration (ß = 0.77, 95% CI = 0.70-0.84, P < 0.0001). Concordance between categorized PrEP intake and TFV-DP concentration was moderate (κ = 0.44, 95% CI = 0.39-0.50). Concordance between self-reported recent PrEP intake and FTC-TP quantifiability was perfect (κ = 0.83, 95% CI 0.76-0.90). CONCLUSION: Self-reported PrEP intake in a diary app is strongly correlated with actual use, and therefore reliable for comparing PrEP adherence between groups. Still, suboptimal criterion validity according to clinically relevant categories warrants caution when assessing 6-week reported adherence for individuals.

What determines mpox vaccination uptake? Assessing the effect of intent-to-vaccinate versus other determinants among men who have sex with men.

BACKGROUND: In response to the mpox outbreak, vaccination was offered in the Netherlands to men who have sex with men (MSM) at increased risk for mpox. Successful vaccination campaigns are leveraged by high intent-to-vaccinate, yet intent might not always lead to uptake. Therefore, we assessed the impact of intent-to-vaccinate and other factors on vaccination uptake among participants of the Amsterdam Cohort Studies (ACS). METHOD: In July 2022, prior to the mpox vaccination campaign, we distributed an online survey regarding mpox intent-to-vaccinate, as well as e.g. beliefs, attitude, subjective norms, and perception of risk among ACS participants (all MSM). Vaccination uptake was self-reported during study visits after August 2022. The association between vaccination intent and uptake, and determinants of intent, was jointly assessed using a structural equation model (SEM) based on components of the Theory of Planned Behavior (TPB). In a second SEM, determinants of intent were allowed to have a direct effect on vaccination uptake. RESULTS: 492 MSM (median age = 46 years) were included in analyses. 380 (77%) had high intent-to-vaccinate and 238 (48%) received at least one vaccine dose. In the first model with a direct relation between intent and uptake only, TBP components predicted intent as expected, and high intent-to-vaccinate was significantly associated with getting vaccinated (ß = 1.1, 95%CI = 0.6-1.5). However, 175/380 (46%) participants with high intent-to-vaccinate did not get vaccinated. The second model had an improved model fit compared to the first model. The effect of intent on uptake was non-significant, and only perceiving to be at higher risk of infection significantly increased vaccination uptake later on (ß = 0.42, 95%CI = 0.26-0.59). Having a steady relationship decreased the probability of vaccination (ß = -0.59, 95%CI = -1.0- -0.18). CONCLUSIONS: While intent-to-vaccinate for mpox was high among MSM, high intent did not necessarily result in vaccine uptake. Mpox risk perception might have played a more pivotal role in getting vaccinated, which may be related to the evolution of vaccination eligibility criteria and accessibility to the vaccine.

Sexual Distancing During 5 Periods Around and During the COVID-19 Pandemic, Amsterdam, the Netherlands.

BACKGROUND: Social and sexual distancing (ie, abstaining from sex with persons outside one's household) was important in the control of the COVID-19 pandemic. Compliance to distancing measures can change over time. We assessed changes in compliance to the sexual distancing measures during five periods of the COVID-19 pandemic in the Netherlands. METHODS: Between November 2021 and March 2022, we used a structured questionnaire containing questions about sexual behavior and factors that could have influenced compliance with sexual distancing. Variables related to sexual behavior were measured for 5 periods, before and during the pandemic, delineated by imposement and relaxation of lockdown measures. RESULTS: Eight hundred seventy participants (predominantly MSM) completed the questionnaire. We found that compliance to the sexual distancing measures decreased over time. The number of casual partners was highest after the lockdown measures were relaxed for the second time (April 2021 to March 2022), and even higher than before the first lockdown. Factors positively associated with sexual distancing compliance were: having confidence in the information provided by the government and experiencing less or similar need for physical contact compared with before the pandemic. Factors that lowered compliance over time were: previously having had COVID-19, perceiving the lockdown measures as overstated, having sex with casual partners and similar drug use during the pandemic as before. CONCLUSIONS: Our findings suggest that sexual distancing measures are difficult to maintain for a long period. Other measures, such as confinement to a small network of known partners, might be more effective for longer pandemics in minimizing the spread of infectious diseases.

Analytical validation and diagnostic performance of the ASCL1/ZNF582 methylation test for detection of high-grade anal intraepithelial neoplasia and anal cancer.

DNA methylation testing on biopsies can detect high-grade anal intraepithelial neoplasia (HGAIN) in need of treatment and anal cancer. This study aimed to analytically validate and determine the diagnostic performance of a newly developed multiplex quantitative methylation-specific PCR, PreCursor-M AnoGYN (RUO), combining ASCL1, ZNF582 and a reference (ACTB) in one assay. Analytical validation was performed on two qPCR devices using predefined quality criteria. Diagnostic performance was determined on a cross-sectional series of 111 anal biopsies covering all stages of anal disease. Differences in methylation levels were assessed using the Kruskal-Wallis test. Area under the curve was determined using logistic regression analysis. Detection rates were calculated at predefined specificities for the cross-sectional and an additional longitudinal series of 23 HGAIN biopsies preceding anal cancer (i.e., progressive HGAIN). For both devices analytical quality criteria were met. ASCL1 and ZNF582 methylation levels increased with increasing severity of disease (p < 6*10-8). Diagnostic performance for AIN3+ was 0.81. All cancers and virtually all progressive HGAIN were detected at 70% and 80% specificity. In conclusion, the ASCL1/ZNF582 methylation test (PreCursor-M AnoGYN (RUO)) was demonstrated to be highly robust and reproducible. Moreover, it had excellent diagnostic accuracy to detect AIN3+ and can potentially be used to guide HGAIN management.

Diagnostic accuracy of qPCR and microscopy for cutaneous leishmaniasis in rural Ecuador: A Bayesian latent class analysis.

BACKGROUND: Clinical and laboratory diagnosis of cutaneous leishmaniasis (CL) is hampered by under-ascertainment of direct microscopy. METHODS: This study compared the diagnostic accuracy of qPCR on DNA extracted from filter paper to the accuracy of direct smear slide microscopy in participants presenting with a cutaneous lesion suspected of leishmaniasis to 16 rural healthcare centers in the Ecuadorian Amazon and Pacific regions, from January 2019 to June 2021. We used Bayesian latent class analysis to estimate test sensitivity, specificity, likelihood ratios (LR), and predictive values (PV) with their 95% credible intervals (95%CrI). The impact of sociodemographic and clinical characteristics on predictive values was assessed as a secondary objective. RESULTS: Of 320 initially included participants, paired valid test results were available and included in the diagnostic accuracy analysis for 129 from the Amazon and 185 from the Pacific region. We estimated sensitivity of 68% (95%CrI 49% to 82%) and 73% (95%CrI 73% to 83%) for qPCR, and 51% (95%CrI 36% to 66%) and 76% (95%CrI 65% to 86%) for microscopy in the Amazon and Pacific region, respectively. In the Amazon, with an estimated disease prevalence among participants of 73%, negative PV for qPCR was 54% (95%CrI 5% to 77%) and 44% (95%CrI 4% to 65%) for microscopy. In the Pacific, (prevalence 88%) the negative PV was 34% (95%CrI 3% to 58%) and 37% (95%CrI 3% to 63%). The addition of qPCR parallel to microscopy in the Amazon increases the observed prevalence from 38% to 64% (+26 (95%CrI 19 to 34) percentage points). CONCLUSION: The accuracy of either qPCR on DNA extracted from filter paper or microscopy for CL diagnosis as a stand-alone test seems to be unsatisfactory and region-dependent. We recommend further studies to confirm the clinically relevant increment found in the diagnostic yield due to the addition of qPCR.

Management of asymptomatic sexually transmitted infections in Europe: towards a differentiated, evidence-based approach.

Most sexually transmitted infections (STIs) can be accurately diagnosed and treated during asymptomatic carriage. Widespread screening for these STIs is therefore assumed to be an effective way to reduce their prevalence and associated disease. In this review, we provide evidence that this is the case for HIV and syphilis. However, for other STIs such as Neisseria gonorrhoeae and Chlamydia trachomatis, our review reveals that the evidence that screening reduces infection prevalence and associated disease is weak. There is also growing evidence of harms from screening that might outweigh any benefits. The harms include the increased consumption of antimicrobials that follows frequent screening and increased detection of asymptomatic STIs in key populations, such as men who have sex with men taking HIV pre-exposure prophylaxis, and associated risk of antimicrobial resistance in target and non-target organisms. There may also be psycho-social harm associated with an STI diagnosis. We conclude that in the absence of symptoms, in high STI prevalence populations frequent STI screening should be limited to HIV and syphilis.

Multi-sensorial perceptions of risk: the aesthetics behind (muco)cutaneous leishmaniasis-related stigma in Ecuador.

Previous research on the stigma associated with cutaneous leishmaniasis, a vector-transmitted parasitic disease, focuses on aesthetic appearance affectation as the leading cause of stigmatisation. However, Indigenous populations in the hinterland of Amazonian Ecuador trigger stigma expressions by recognising (muco)cutaneous leishmaniasis, primarily through atypical smell, followed by the odd voice sound, appearance and taste. This empirical way of recognising symptoms relies on embodied forms of identifying a disease, contrasting the Western supremacy of visuality and demanding to be understood via multi-sensorial anthropology. Through ethnographic research and data retrieved from eighty-three semistructured interviews and fifteen focus groups in seven Ecuadorian ethnic groups - including six Indigenous groups in the Amazon region - this paper analyses how the sensorium is a health thermometer. Findings reveal that differentiated cultural responses to a sense of peril, contagion and social (self)rejection, understood as stigma expressions, are linked to the holistic approach to health (or well-being) shared by Indigenous populations. In forest societies, well-being is explained through successful (non-)human relationships, and disease permeates through bodies that lack balanced relations.

Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV+ Men.

PURPOSE: Anal cancer is increasing in HIV+ men who have sex with men (MSM). Treatment options for its precursor, high-grade anal intraepithelial neoplasia (HGAIN), are suboptimal. In this phase I to II dose-finding study, we assessed the safety and efficacy of the human papillomavirus type 16 (HPV16) synthetic long peptide vaccine (SLP-HPV-01) in HIV+ MSM with HPV16-positive HGAIN. PATIENTS AND METHODS: Four dosage schedules (1-5-10; 5-10-20; 10-20-40; and 40-40-40-40 µg) of SLP-HPV-01 were administered intradermally with a 3-week interval in 10 patients per dose level (DL). In each dose group, 5 patients also received 1 µg/kg pegylated IFNα-2b subcutaneously. Primary endpoints were safety and regression of HGAIN at 3, 6, and 12 months. RESULTS: Eighty-one of 134 screened patients (60%) had HPV16-negative HGAIN lesions, leaving 53 eligible patients. Thirteen patients were excluded, leaving 40 men. The vaccine was well tolerated. One patient developed a generalized rash. The highest dosage level induced the strongest immune responses. There was no indication for stronger reactivity in the IFNα groups. Up to 18 months of follow-up, 8/38 intention-to-treat patients had a complete clinical and histologic response and one had a partial response (in total 9/38, 23.7%). At the highest dosage level, the clinical response was 4/10 (40%). Stronger immune responses were detected among clinical responders. CONCLUSIONS: The highest DL is safe, immunogenic, and associated with clinical responses to HPV16-induced lesions. However, as the majority of HGAIN is caused by the other HPV types, further studies should aim at pan-HPV vaccination to prevent or treat HGAIN.

Timely Diagnosis of Incubating Syphilis Infections Using Treponema pallidum Transcription-Mediated Amplification Assay.

BACKGROUND: Syphilis is a complex, multistage, sexually transmitted infection (STI) caused by the bacterium Treponema pallidum subspecies pallidum (TP). New diagnostic tools are needed to minimize transmission. In this study, we aimed to assess the additional value of an investigational transcription-mediated amplification test for TP (TP-TMA) for routine diagnostics. METHODS: Between September 2021 and August 2022, visits by all participants of the national preexposure prophylaxis (PrEP) program at the sexual health center (SHC) in Amsterdam were included. Anal, pharyngeal, vaginal, and urine samples collected for Chlamydia trachomatis and Neisseria gonorrhoeae screening were additionally tested with the TP-TMA assay based on detection of 23S rRNA of TP. RESULTS: In total, 9974 SHC visits by 3283 participants were included. There were 191 infectious syphilis cases diagnosed: 26 (14%) primary syphilis, 54 (29%) secondary syphilis, and 111 (58%) early latent syphilis. In 79 of the 191 (41%) syphilis cases, at least 1 sample was TP-TMA-positive. For 16 participants, the positive TP-TMA result was not concordant with routine diagnostics. Of those, 2 participants were treated for syphilis within a week before the visit. Eight participants were treated for a syphilis notification at the visit or for another STI. Five participants were diagnosed with syphilis at the following visit, and 1 participant was lost to follow-up. CONCLUSIONS: By adding the TP-TMA assay to routine diagnostics, we identified 14 of 191 (7%) additional syphilis infections among participants of the national PrEP program. The TP-TMA assay is a useful diagnostic tool to increase syphilis case finding and thus limit the transmission of syphilis.

Trajectories of PrEP use among men who have sex with men: a pooled analysis of two prospective, observational cohort studies.

INTRODUCTION: Daily and event-driven oral pre-exposure prophylaxis (PrEP) reduce the risk of HIV acquisition. PrEP use can vary over time, yet little is known about the trajectories of PrEP use irrespective of the chosen PrEP regimens among men who have sex with men (MSM). METHODS: Using data from a mobile, web-based diary application collected daily from 17 August 2015 until 6 May 2018, we analysed PrEP use and sexual behaviour in two large cohorts, AMPrEP (Amsterdam, the Netherlands) and Be-PrEP-ared (Antwerp, Belgium). In both cohorts, participants could choose between daily and event-driven oral PrEP every 3 months. We used group-based trajectory modelling to identify trajectories of PrEP use over time and their determinants. In addition, we estimated the incidence rate of chlamydia, gonorrhoea and syphilis within these trajectories. RESULTS: We included 516 MSM (n = 322 AMPrEP; n = 194 Be-PrEP-ared), of whom 24% chose event-driven PrEP at PrEP initiation. Participants contributed 225,015 days of follow-up (median = 508 days [IQR = 429-511]). Four distinct PrEP use trajectories were identified: ≤2 tablets per week ("low frequency," 12% of the total population), 4 tablets per week ("variable," 17%), "almost daily" (31%) and "always daily" (41%). Compared to participants with "low frequency" PrEP use, participants with "variable" (odds ratio [OR] = 2.18, 95% confidence interval [CI] = 1.04-4.60) and "almost daily" PrEP use were more often AMPrEP participants (OR = 2.64, 95% CI = 1.27-5.49). "Almost daily" PrEP users were more often employed (OR = 6.76, 95% CI = 2.10-21.75) and were younger compared to participants with "low frequency" PrEP use. In addition, the number of days on which anal sex occurred was lower among participants with "low frequency" PrEP use compared to the other groups (all p<0.001). Compared to "low frequency" PrEP users, the incidence rates of chlamydia and gonorrhoea were higher for participants with "almost daily" and "always daily" PrEP use. CONCLUSIONS: We uncovered four distinct PrEP use trajectories, pointing to different patterns of PrEP use in practice beyond the two-regimen dichotomy. These trajectories were related to sexual behaviour and rates of sexually transmitted infection. Tailoring PrEP care according to different PrEP use patterns could be an important strategy to improve efficient PrEP delivery.

Bacterial sexually transmitted infections are concentrated in subpopulations of men who have sex with men using HIV pre-exposure prophylaxis.

OBJECTIVE: Studies have shown varying trends in incidence of sexually transmitted infections (STIs) among individuals using HIV pre-exposure prophylaxis (PrEP). Characterization of individuals at increased risk for STIs may offer an opportunity for targeted STI screening. DESIGN: Group-based trajectory modeling. METHODS: We screened participants from the AMPrEP demonstration project (2015-2020) for urogenital, anal, and pharyngeal chlamydia and gonorrhea, and syphilis every 3 months and when needed. We identified trajectories of STI incidence within individuals over time and determinants of belonging to a trajectory group. We calculated cumulative proportions of STIs within STI trajectory groups. RESULTS: Three hundred and sixty-six participants with baseline and at least one screening visit during follow-up were included (median follow-up time = 3.7 years [interquartile range, IQR = 3.5-3.7]). We identified three trajectories of STI incidence: participants with a mean of approximately 0.1 STIs per 3 months ('low overall', 52% of the population), participants with a mean 0.4 STI per 3 months ('medium overall', 43%), and participants with high and fluctuating (between 0.3 and 1 STIs per 3 months) STI incidence ('high and fluctuating', 5%). Participants in the 'low overall' trajectory were significantly older, and reported less chemsex and condomless anal sex with casual partners than participants in the other trajectories. Participants in the 'high and fluctuating' and 'medium overall' groups accounted for respectively 23 and 64% of all STIs observed during follow-up. CONCLUSIONS: STI incidence was concentrated in subpopulations of PrEP users who were younger, had more chemsex and condomless anal sex. Screening frequency for STIs could be reduced for subpopulations with low risk for incident STIs.

Leishmania species and clinical characteristics of Pacific and Amazon cutaneous leishmaniasis in Ecuador and determinants of health-seeking delay: a cross-sectional study.

BACKGROUND: Cutaneous Leishmaniasis (CL) affects up to 5.000 people in Ecuador each year. L. guyanensis and L. braziliensis are the most common of the eight CL-causing Leishmania species. Earlier CL research concentrated on the easily accessible Pacific region. This study aims to describe the Leishmania species in Pacific and Amazon ecoregions, to analyze regional differences in CL patient clinical presentation, and to identify determinants of health-seeking delay. METHODS: All cases in this cross-sectional study were diagnosed using smear slide microscopy, PCR, or both. Cytochrome B gene sequencing was used to identify the causative Leishmania species in qPCR-positive samples. RESULTS: This study included 245 patients, with 154 (63%) infected in the Pacific region and 91 (37%) infected in the Amazon. Causative Leishmania species were identified in 135 patients (73% of qPCR positives). L. guyanensis was identified in 76% (102/135) of the samples and L. braziliensis in 19% (26/135). The Pacific region had a low prevalence of 6% (5/89) of L. braziliensis. For the first time, we report L. guyanensis from the central Amazon, L. braziliensis from the northern Pacific, and L. lainsoni from both the central Amazon and northern Pacific. Amazon cases had a longer median health-seeking delay in months (2.0, IQR 3.0) than Pacific cases (1.0, IQR 1.5). Prolonged health-seeking delay was associated with older age, Amerindian ethnicity, infection at lower altitudes, non-ulcerative lesions, and lesions on the lower limbs. CONCLUSIONS: In the Pacific region, health-seeking delay is relatively short and L. braziliensis prevalence remains low. Limited access to health care and stigma might explain the prolonged health-seeking delay in the Amazon. We recommend larger studies on the distribution of Leishmania species in Amazon CL cases and additional regional research into diagnostic test accuracy. Furthermore, the determinants of health-seeking delay in Ecuador should be investigated further.

Treponema pallidum Strains Among Women and Men Who Have Sex With Women in Amsterdam, the Netherlands and Antwerp, Belgium Between 2014 and 2020.

ABSTRACT: The Treponema pallidum strain distribution among men who have sex with women were similar to the strain distribution men who have sex with men. The most prevalent strains and percentage of strains belonging to the Nichols lineage are similar to previous studies in Amsterdam focusing on men who have sex with men.

Effect of the introduction of screening for cancer precursor lesions on anal cancer incidence over time in people living with HIV: a nationwide cohort study.

BACKGROUND: Incidence of anal cancer is high in people living with HIV, particularly in men who have sex with men (MSM). Screening for and treatment of precursor lesions might prevent progression to anal cancer in people living with HIV. We examined trends in incidence of and mortality after anal cancer diagnosis in people living with HIV, including the effect of screening from 2007 onwards, in the Netherlands. METHODS: In this observational cohort study, we analysed data from the ongoing open nationwide Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. We included all consenting adults living with HIV and identified all primary anal squamous cell carcinoma. We reported temporal trends in incident anal cancer cases from Jan 1, 1996, to Dec 31, 2020, and all-cause and anal cancer-related mortality in individuals diagnosed with anal cancer. Multivariable Poisson regression was used to explore risk factors for incident anal cancer and multivariable Cox regression was used to explore risk factors for anal cancer-related mortality. FINDINGS: Among 28 175 individuals in HIV care (59·7% MSM), 227 primary anal cancer cases were diagnosed. Despite the increasing average age of the cohort, crude incidence rates of anal cancer in MSM declined slowly over time, from 107·0 (95% CI 75·7-147·0) per 100 000 person-years in 1996-2005 to 93·7 (75·3-115·0) per 100 000 person-years in 2013-20 (p=0·49). Crude incidence rates in men who do not have sex with men (non-MSM) and women were generally lower than in MSM, but increased slightly over time, from 51·08 (95% CI 20·54-105·25) to 67·82 (40·83-105·91; p=0·52) per 100 000 person-years in non-MSM and from 8·09 (0·20-45·06) to 24·95 (10·03-51·40; p=0·29) per 100 000 person-years in women. The age-adjusted incidence rate in MSM in 2013-20 was significantly lower (rate ratio 0·62 [95% CI 0·41-0·92]) compared with in 1996-2005. Changes in risk factors (less smoking, cumulative exposure to CD4 count of <200 cells per µL, and plasma HIV-1 RNA of >1000 copies per mL) mostly explained the decrease in anal cancer risk over time in MSM. 3866 (23·0%) of 16 819 MSM participated in anal cancer screening at least once. TNM tumour staging was more favourable (Cochrane-Armitage test for trend p=0·033) in individuals diagnosed during screening. Crude anal cancer-associated 5-year mortality in people living with HIV decreased from 30·4% (1996-2005) to 18·3% (2013-20; odds ratio 0·48; p=0·070). Anal cancer-related mortality was 3·7% (95% CI 0·5-23·5) in all men who had been screened and 24·0% (95% CI 18·1-31·3) in men who had not been screened (p=0·023). In men, screening participation (hazard ratio [HR] 0·31, p=0·051) and cumulative exposure to CD4 counts of less than 200 cells per µL (HR 1·11 per year; p=0·0022) were independently associated with anal cancer-related mortality. INTERPRETATION: As anal cancer incidence is slowly declining in MSM but not in non-MSM and women, health-care professionals should not focus only on MSM for anal cancer prevention. Men diagnosed with anal cancer during screening had improved survival, probably because they were diagnosed at an earlier disease stage. Next to preventing anal cancer, these data are an important justification to screen those most at risk of anal cancer. FUNDING: None.

The impact of COVID-19-related restrictions in 2020 on sexual healthcare use, pre-exposure prophylaxis use, and sexually transmitted infection incidence among men who have sex with men in Amsterdam, the Netherlands.

OBJECTIVES: We studied the effects of restrictions related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) pandemic on the use of sexual healthcare and pre-exposure prophylaxis (PrEP) and on the incidence of sexually transmitted infections (STIs) among men who have sex with men (MSM) in a prospective, open-label PrEP demonstration study (AMPrEP) in Amsterdam, the Netherlands. METHODS: We retrieved data from 2019 to 2020 for participants with one or more study visit in 2019 (n = 305) and from two COVID-19 questionnaires (2020: n = 203; 2021: n = 160). Analyses were stratified for three periods of pandemic-related restrictions (first: 15 March 2020-15 June 2020; second: 16 June 2020-15 September 2020; third: 16 September 2020-31 December 2020 or 1 April 2021 for the COVID-19 questionnaire). Endpoints included returning for care during the pandemic, PrEP use (increased/unchanged vs. deceased/stopped, relative to 2019), and any STI/HIV. We modelled determinants of care and PrEP use via multivariable logistic regression and STI incidence using piecewise Poisson regression, comparing the 2020 and 2019 periods. RESULTS: Of the 305 MSM included in the analysis, 72.8% returned for care during the pandemic, and this was significantly more likely among daily (vs. event-driven) PrEP users (p < 0.001). Increased/unchanged PrEP use ranged from 55.2% to 58.1% across the three pandemic periods and was more likely among those reporting chemsex in the first (p = 0.001) and third (p = 0.020) periods and among those reporting an increased/unchanged number of sex partners during the second period (p = 0.010). STI incidence was significantly lower in 2020 than in 2019 during the first period (incidence rate ratio [IRR] 0.43; 95% confidence interval [CI] 0.28-0.68) and not significantly different during the second (IRR 1.38; 95% CI 0.95-2.00) and third (IRR 1.42; 95% CI 0.86-2.33) periods. No HIV was diagnosed. CONCLUSION: COVID-19-related restrictions coincided with reduced care and PrEP use. Changes in STI incidence suggest delayed diagnoses. Ways to ensure continued access to sexual healthcare during restrictions are needed.

Can we screen less frequently for STI among PrEP users? Assessing the effect of biannual STI screening on timing of diagnosis and transmission risk in the AMPrEP Study.

BACKGROUND: In 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. METHODS: Using 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. RESULTS: We 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)). CONCLUSION: Reducing 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.

Eligibility criteria vs. need for pre-exposure prophylaxis: a reappraisal among men who have sex with men in Amsterdam, the Netherlands.

To reappraise pre-exposure prophylaxis (PrEP) eligibility criteria towards the men who have sex with men (MSM) with highest HIV-risk, we assessed PrEP need (i.e. HIV-risk) using Amsterdam Cohort Studies data from 2011-2017 for all non-PrEP using MSM. Outcomes were incident HIV-infection and newly-diagnosed anal STI. Determinants were current PrEP eligibility criteria (anal STI and condomless sex (CAS)) and additional determinants (age, education, group sex, alcohol use during sex and chemsex). We used targeted maximum likelihood estimation (TMLE) to estimate the relative risk (RR) and 95% confidence intervals (CI) of determinants on outcomes, and calculated population attributable fractions (PAFs) with 95% CI using RRs from TMLE. Among 810 included MSM, 22 HIV-infections and 436 anal STIs (n = 229) were diagnosed during follow-up. Chemsex (RR = 5.8 (95% CI 2.0-17.0); PAF = 55.3% (95% CI 43.3-83.4)), CAS with a casual partner (RR = 3.3 (95% CI 1.3-8.7); PAF = 38.0% (95% CI 18.3-93.6)) and anal STI (RR = 5.3 (95% CI 1.7-16.7); PAF = 22.0 (95% CI -16.8 to 100.0)) were significantly (P < 0.05) associated with and had highest attributable risk fractions for HIV. Chemsex (RR = 2.0 (95% CI 1.6-2.4); PAF = 19.5 (95% CI 10.6-30.6)) and CAS with a casual partner (RR = 2.5 (95% CI 2.0-3.0); PAF = 28.0 (95% CI 21.0-36.4)) were also significantly associated with anal STI, as was younger age (16-34/≥35; RR = 1.7 (95% CI 1.4-2.1); PAF = 15.5 (95% CI 6.4-27.6)) and group sex (RR = 1.3 (95% CI 1.1-1.6); PAF = 9.0 (95% CI -2.3 to 23.7)). Chemsex should be an additional PrEP eligibility criterion.

[Monkeypox, a new pandemic?] / Uitbraak van monkeypox: een nieuwe pandemie?

Monkeypox (MPX) is a disease caused by the monkeypox virus. It is a viral zoonotic disease, endemic in Central and West Africa. Human-to-human spread also occurs and is a feature of the current global outbreak. As far as we know, exponential transmission during this outbreak is not related to changed viral characteristics but due to multiple high-risk contacts in a subset of people that have contracted the virus, so far almost exclusively affecting men who have sex with men (MSM). Appropriate public health measures and increased alertness of all health care providers is needed to increase case-finding and decrease transmission. There is a real chance of MPX to become endemic in large parts of the world.

Cutaneous Leishmaniasis: A 2022 Updated Narrative Review into Diagnosis and Management Developments.

This review is an update of an earlier narrative review published in 2015 on developments in the clinical management of cutaneous leishmaniasis (CL) including diagnosis, treatment, prevention and control measurements. CL is a vector-borne infection caused by the protozoan parasite Leishmania. The vector is the female sandfly. Globally, CL affects 12 million cases and annually 2 million new cases occur. CL is endemic in almost 100 countries and the total risk population is approximately 350 million people. WHO lists CL an emerging and uncontrolled disease and a neglected tropical disease. Local experience-based evidence remains the mainstay for the management of CL. Whereas intralesional therapeutic options are the first treatment option for most CL patients, those with mucocutaneous and disseminated involvement require a systemic therapeutic approach. Moreover, different Leishmania species can vary in their treatment outcomes. Therefore, species determination is critical for optimal CL clinical management. New DNA techniques allow for relatively easy Leishmania species determination, yet they are not easily implemented in resource-limited settings. There is a desperate need for novel, less toxic, and less painful treatment options, especially for children with CL. Yet, the large and well conducted studies required to provide the necessary evidence are lacking. To further control and potentially eliminate CL, we urgently need to improve vector control, and diagnostics, and we require efficient and safe vaccines. Alas, since CL primarily affects poor people, biotechnical companies dedicate little investment into the research programs that could lead to diagnostic, pharmaceutical, and vaccine innovations.