Decreased Time to Viral Suppression After Implementation of Targeted Testing and Immediate Initiation of Treatment of Acute Human Immunodeficiency Virus Infection Among Men Who Have Sex With Men in Amsterdam.

BACKGROUND: Men who have sex with men (MSM) with acute human immunodeficiency virus (HIV) infection (AHI) are a key source of new infections. To curb transmission, we implemented a strategy for rapid AHI diagnosis and immediate initiation of combination antiretroviral therapy (cART) in Amsterdam MSM. We assessed its effectiveness in diagnosing AHI and decreasing the time to viral suppression. METHODS: We included 63 278 HIV testing visits in 2008-2017, during which 1013 MSM were diagnosed. Standard of care (SOC) included HIV diagnosis confirmation in < 1 week and cART initiation in < 1 month. The AHI strategy comprised same-visit diagnosis confirmation and immediate cART. Time from diagnosis to viral suppression was assessed for 3 cART initiation periods: (1) 2008-2011: cART initiation if CD4 < 500 cells/µL (SOC); (2) January 2012-July 2015: cART initiation if CD4 < 500 cells/µL, or if AHI or early HIV infection (SOC); and (3a) August 2015-June 2017: universal cART initiation (SOC) or (3b) August 2015-June 2017 (the AHI strategy). RESULTS: Before implementation of the AHI strategy, the proportion of AHI among HIV diagnoses was 0.6% (5/876); after implementation this was 11.0% (15/137). Median time (in days) to viral suppression during periods 1, 2, 3a, and 3b was 584 (interquartile range [IQR], 267-1065), 230 (IQR, 132-480), 95 (IQR, 63-136), and 55 (IQR, 31-72), respectively (P < .001). CONCLUSIONS: Implementing the AHI strategy was successful in diagnosing AHI and significantly decreasing the time between HIV diagnosis and viral suppression.

Evaluation of the Hepatitis C Testing Strategy for Human Immunodeficiency Virus-Positive Men Who Have Sex With Men at the Sexually Transmitted Infections Outpatient Clinic of Amsterdam, the Netherlands.

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.

Sexually transmissible infections among female sex workers in Amsterdam between 2011 and 2016: does risk vary by work location?

Background Female sex workers (FSW) are at risk for sexually transmissible infections (STI). This study aimed to investigate whether the risk for chlamydia and gonorrhoea differs by work location among FSW in Amsterdam. Additionally, trends in STI positivity rates between 2011 and 2016 were assessed. METHODS: This was a retrospective analysis of routinely collected clinical data during STI consultations of FSW by the Prostitution and Healthcare Centre (P&G292). Work location was categorised as window prostitution, escorts/homeworkers, clubs/brothels/private houses/massage salons and other. RESULTS: In total, 7558 STI consultations of 2529 FSW in the period 2011-16 were included. Positivity rates for chlamydia and gonorrhoea were 6.6% and 2.0%, respectively. Infectious hepatitis B virus, syphilis and HIV were diagnosed in <0.2% of consultations. Positivity rates of chlamydia and rectal gonorrhoea differed significantly by work location (P < 0.001). Genital and rectal chlamydia and rectal gonorrhoea were significantly less likely among women working in window prostitution, except for the other-group. Risk factors for STI did not vary by work location. Among women working in window prostitution, positivity rates for oropharyngeal and genital chlamydia and genital gonorrhoea were significantly decreasing between 2011 and 2016 (P trend <0.05). CONCLUSIONS: The higher STI positivity among escorts/homeworkers and FSW in clubs/brothels/private houses/massage salons emphasises the need for extra attention to improve condom use and STI testing in this group. Factors associated with STI did not vary by work location, thus interventions, including those used by P&G292, to reduce STI risk, can be used for women at all work locations.

Participation, retention, and associated factors of women in a prospective multicenter study on Chlamydia trachomatis infections (FemCure).

Prospective studies are key study designs when attempting to unravel health mechanisms that are widely applicable. Understanding the internal validity of a prospective study is essential to judge a study's quality. Moreover, insights in possible sampling bias and the external validity of a prospective study are useful to judge the applicability of a study's findings. We evaluated participation, retention, and associated factors of women in a multicenter prospective cohort (FemCure) to understand the study's validity.Chlamydia trachomatis (CT) infected adult women, negative for HIV, syphilis, and Neisseria gonorrhoeae were eligible to be preselected and included at three sexually transmitted infection (STI) clinics in the Netherlands (2016-2017). The planned follow-up for participants was 3 months, with two weekly rectal and vaginal CT self-sampling and online questionnaires administered at home and at the clinic. We calculated the proportions of preselected, included, and retained (completed follow-up) women. Associations with non-preselection, noninclusion, and non-retention (called attrition) were assessed (logistic and Cox regression).Among the 4,916 women, 1,763 (35.9%) were preselected, of whom 560 (31.8%) were included. The study population had diverse baseline characteristics: study site, migration background, high education, and no STI history were associated with non-preselection and noninclusion. Retention was 76.3% (n = 427). Attrition was 10.71/100 person/month (95% confidence interval 9.97, 12.69) and was associated with young age and low education. In an outpatient clinical setting, it proved feasible to include and retain women in an intensive prospective cohort. External validity was limited as the study population was not representative (sampling bias), but this did not affect the internal validity. Selective attrition, however (potential selection bias), should be accounted for when interpreting the study results.

Letter to the editor: female sex workers and HPV vaccine.

When considering what the scientific evidence is for the potential added value to offer HPV vaccines to sex workers, not only its potential role for female sex workers should be examined, but its role for all those who conduct sex work. Our initial paper looked at the evidence in terms of HPV vaccine immunogenicity, efficacy, effect on transmission, induction of mucosal immunity, and not at implementation. Brown and Cabral considered our omission to address the aspects of implementation an 'academic mistake'. We disagree; implementation aspects are complex and require analyses of multiple barriers, and how to address these. It only makes sense to discuss these if there is scientific evidence for its implementation; otherwise offering the vaccine is not useful.

Diverging trends in incidence of HIV versus other sexually transmitted infections in HIV-negative MSM in Amsterdam.

OBJECTIVES: We investigated changes in incidence rates of HIV and sexually transmitted infections (STIs) and trends in sexual behavior in MSM from 2009 to 2017. DESIGN: Open prospective cohort study. METHODS: HIV-negative MSM enrolled in the Amsterdam Cohort Studies were included. Participants semiannually completed a questionnaire on sexual behavior and were tested for HIV-1, syphilis, and urethral, anal and pharyngeal chlamydia and gonorrhea. Time trends in incidence rates were analyzed using exponential survival models. RESULTS: During follow-up, 42 of 905 MSM acquired HIV. The HIV incidence rate was 1.9/100 person-years [95% confidence interval (CI) 1.0-3.7] in 2009 and decreased to 0.5/100 person-years (95% CI 0.2-1.4) in 2017 (P = 0.03). The largest decrease was observed in participants aged at least 35 years (P = 0.005), while the trend remained stable in 18-34 year olds (P = 0.4). The incidence rate for any bacterial STI was 16.8/100 person-years (95% CI 13.4-21.0) in 2010, and increased to 33.1/100 person-years (95% CI 29.0-37.9) in 2017 (P < 0.001). Between 2009 and 2017, the percentage reporting condomless anal sex with casual partners increased from 26.9 to 39.4% (P < 0.001), and the mean number of casual partners from eight (95% CI 8-8) to 11 (95% CI 10-11) (P = 0.05). Condomless anal sex with steady partner(s) remained stable over time (P = 0.5). CONCLUSION: Among MSM in Amsterdam, incidence rates of HIV versus other STI show diverging trends. The increase in STI incidence coincides with a decrease in condom use with casual partners. The decrease in HIV incidence, despite increased sexual risk behavior, suggests that other HIV prevention methods have been successful in reducing HIV transmission among MSM.

Sexual behaviour and incidence of HIV and sexually transmitted infections among men who have sex with men using daily and event-driven pre-exposure prophylaxis in AMPrEP: 2 year results from a demonstration study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) for HIV might induce risk compensation, defined as increased sexual risk behaviour leading to increased incidence of bacterial sexually transmitted infections (STIs). We examined the incidence of HIV, STIs, and sexual behaviour after initiating daily and event-driven PrEP. METHODS: AMPrEP is a demonstration study that assessed the incidence of HIV and bacterial STIs and sexual behaviour among PrEP users at the STI clinic of the Public Health Service of Amsterdam (Amsterdam, the Netherlands). Eligible adults (aged ≥18 years) were HIV-negative men who have sex with men (MSM) and transgender people who had reported one or more of the following in the previous 6 months: condomless anal sex with casual partners, at least one bacterial STI, use of post-exposure prophylaxis after a sexual risk incident, or an HIV-positive sexual partner with detectable viral load. Participants were given a choice of daily PrEP or event-driven PrEP regimens. Participants were seen every 3 months for HIV and STI testing. Participants also completed self-administered questionnaires about sexual behaviour at each visit. Over the first 2 years, we assessed the number and incidence rate of HIV and chlamydia, gonorrhoea, and syphilis, including STIs diagnosed in between study visits and assessed changes in incidence over time using piecewise exponential survival models. The number of sexual acts and sexual partners were also analysed and changes over time were assessed using negative binomial regression models. This study is ongoing; the data cutoff for this analysis was June 30, 2018. FINDINGS: Between Aug 3, 2015, and May 31, 2016, 376 participants were recruited, of whom nine participants were lost to follow-up, thus 367 participants were included in the analysis. Overall, 365 MSM and two transgender women were included, contributing 681·7 person-years of follow-up. At enrolment, 269 (73%) of 367 participants chose daily PrEP and 98 (27%) participants chose event-driven PrEP. Two individuals in the daily PrEP group became HIV-positive; overall HIV incidence rate was 0·30 per 100 person-years (95% CI 0·07-1·19). 253 participants were diagnosed with one or more STI during the first 2 years (incidence rate 90·4 per 100 person-years). STI incidence did not change over time (adjusted incidence rate ratio [aIRR] 1·00 per 3 month follow-up, 95% CI 0·93-1·07). More than a quarter of all STIs were diagnosed from tests done in between study visits. STI incidence was lower in the event-driven PrEP group than the daily PrEP group (aIRR 0·59, 95% CI 0·46-0·75). The number of condomless anal sex acts with casual partners per 3 months increased, but the number of partners and sex acts remained stable. INTERPRETATION: Although the overall incidence of STIs did not change during 2 years of PrEP use, the incidence of STIs was higher among participants using daily PrEP than those using event-driven PrEP, which is likely a result of differences in sexual behaviour. This finding suggests the need to tailor STI prevention interventions according to behavioural profiles. FUNDING: ZonMw, H-TEAM, Internal GGD research funds, Aidsfonds, Stichting AmsterdamDiner Foundation, Gilead Sciences, Janssen Pharmaceutica, M A C AIDS Fund, and ViiV Healthcare.

Should female sex workers be offered HPV vaccination?

Prophylactic vaccines are efficacious in preventing Human Papillomavirus (HPV) infection and subsequent cervical intraepithelial neoplasia (CIN), cervical cancer, other anogenital cancers, and anogenital warts. Female sex workers (SW) are at increased risk of acquiring sexually transmitted infections, including HPV. There are several reasons to offer HPV vaccination to SW: they are at high risk for HPV and often unvaccinated, and the immunogenicity of the vaccine is also excellent in previously HPV exposed women. Furthermore, women with disease caused by HPV may still benefit from vaccination. The efficacy of vaccinating mid-adult women (26-44 years old) against persistent HPV infection and CIN2+ is good. Although an SW may have been infected or exposed to HPV, she may not have been exposed to all vaccine-included hrHPV types. Vaccination induces mucosal immunity via the production of neutralizing antibodies on the surface of the female genital tract, thus preventing potential transmission to clients. Nevertheless, some considerations argue against offering vaccination to SWs. Current vaccines are only prophylactic and as such, do not affect current HPV infections. Women who have previously cleared HPV infections, may do so again and thus not need vaccination. Fewer SW might be naïve to HPV-types than currently thought. HPV vaccination has probably no effect on latent infections. Vaccinating sometime after sexual debut could be too late, as infections have already occurred. Taken together, some data suggest that vaccination of SW may offer health benefits, also for the community, but sufficient evidence is lacking. In certain cases, HPV vaccination of SW may be recommended. Evidence-based, public health decisions concerning vaccination of SW are challenging and could be facilitated with more research in this high-risk group.

Hepatitis A incidence, seroprevalence, and vaccination decision among MSM in Amsterdam, the Netherlands.

BACKGROUND: Several outbreaks of Hepatitis A virus (HAV) were recently documented among men who have sex with men (MSM) in Europe. We investigated the HAV incidence among MSM in Amsterdam, the Netherlands; and HAV seroprevalence and HAV vaccination decision among MSM visiting the Sexually Transmitted Infection (STI) clinic in Amsterdam. METHODS: Using surveillance data from 1992 to 2017 of MSM with acute HAV in Amsterdam, we estimated the incidence by calendar year and age. We explored HAV seroprevalence by calendar year and age, determinants for HAV seropositivity, and opting-in/out for HAV vaccination using data collected among MSM that visited the STI clinic between 2006 and 2017 and were included in a nationwide Hepatitis B virus (HBV) vaccination programme. Offering HAV vaccination at the STI clinic differed over three consecutive periods: not offered, offered for free, or offered for 75 euros. Logistic regression analyses were used to explore determinants. RESULTS: HAV incidence increased in 2016/17 after 4 years of absence and peaked in MSM around 35 years of age. Among MSM visiting the STI clinic, HAV seroprevalence was 37% (95%CI = 35-40%), which was constant over the period 2006-2017, and increased with age (p < 0.001). Determinants for HAV seropositivity in multivariable analysis were: older age (p < 0.001), originating from an HAV endemic country (p < 0.001), and being HBV seropositive (p = 0.001). MSM opted-in more frequently when HAV vaccination was offered for free versus paid (89% versus 11%, respectively; p < 0.001). Younger MSM were less inclined to vaccinate when payment was required (p = 0.010). Post-hoc analyses showed that 98% versus 46% of MSM visiting the Amsterdam STI clinic would be protected against HAV infection if HAV vaccination was offered for free or for 75 euros, respectively. CONCLUSIONS: The MSM population of Amsterdam is vulnerable to a new HAV outbreak. We strongly recommend that MSM have access to free hepatitis A vaccination.

Treatment Effectiveness of Azithromycin and Doxycycline in Uncomplicated Rectal and Vaginal Chlamydia trachomatis Infections in Women: A Multicenter Observational Study (FemCure).

BACKGROUND: Rectal infections with Chlamydia trachomatis (CT) are prevalent in women visiting a sexually transmitted infection outpatient clinic, but it remains unclear what the most effective treatment is. We assessed the effectiveness of doxycycline and azithromycin for the treatment of rectal and vaginal chlamydia in women. METHODS: This study is part of a prospective multicenter cohort study (FemCure). Treatment consisted of doxycycline (100 mg twice daily for 7 days) in rectal CT-positive women, and of azithromycin (1 g single dose) in vaginally positive women who were rectally untested or rectally negative. Participants self-collected rectal and vaginal samples at enrollment (treatment time-point) and during 4 weeks of follow-up. The endpoint was microbiological cure by a negative nucleic acid amplification test at 4 weeks. Differences between cure proportions and 95% confidence intervals (CIs) were calculated. RESULTS: We analyzed 416 patients, of whom 319 had both rectal and vaginal chlamydia at enrollment, 22 had rectal chlamydia only, and 75 had vaginal chlamydia only. In 341 rectal infections, microbiological cure in azithromycin-treated women was 78.5% (95% CI, 72.6%-83.7%; n = 164/209) and 95.5% (95% CI, 91.0%-98.2%; n = 126/132) in doxycycline-treated women (difference, 17.0% [95% CI, 9.6%-24.7%]; P < .001). In 394 vaginal infections, cure was 93.5% (95% CI, 90.1%-96.1%; n = 246/263) in azithromycin-treated women and 95.4% (95% CI, 90.9%-98.2%; n = 125/131) in doxycycline-treated women (difference, 1.9% [95% CI, -3.6% to 6.7%]; P = .504). CONCLUSIONS: The effectiveness of doxycycline is high and exceeds that of azithromycin for the treatment of rectal CT infections in women. CLINICAL TRIALS REGISTRATION: NCT02694497.

Relation between Chlamydia trachomatis infection and pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility in a Dutch cohort of women previously tested for chlamydia in a chlamydia screening trial.

OBJECTIVES: A better understanding of Chlamydia trachomatis infection (chlamydia)-related sequelae can provide a framework for effective chlamydia control strategies. The objective of this study was to estimate risks and risk factors of pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility (TFI) with a follow-up time of up until 8 years in women previously tested for chlamydia in the Chlamydia Screening Implementation study (CSI) and participating in the Netherlands Chlamydia Cohort Study (NECCST). METHODS: Women who participated in the CSI 2008-2011 (n=13 498) were invited in 2015-2016 for NECCST. Chlamydia positive was defined as a positive CSI-PCR test, positive chlamydia serology and/or self-reported infection (time dependent). Data on PID, ectopic pregnancy and TFI were collected by self-completed questionnaires. Incidence rates and HRs were compared between chlamydia-positive and chlamydia-negative women corrected for confounders. RESULTS: Of 5704 women included, 29.5% (95% CI 28.3 to 30.7) were chlamydia positive. The incidence rate of PID was 1.8 per 1000 person-years (py) (1.6 to 2.2) overall, 4.4 per 1000 py (3.3 to 5.7) among chlamydia positives compared with 1.4 per 1000 py (1.1 to 1.7) for chlamydia negatives. For TFI, this was 0.4 per 1000 py (0.3 to 0.5) overall, 1.3 per 1000 py (0.8 to 2.1) and 0.2 per 1000 py (0.1 to 0.4) among chlamydia positives and negatives, respectively. And for ectopic pregnancy, this was 0.6 per 1000 py (0.5 to 0.8) overall, 0.8 per 1000 py (0.4 to 1.5) and 0.6 per 1000 py (0.4 to 0.8) for chlamydia negatives. Among chlamydia-positive women, the strongest risk factor for PID was symptomatic versus asymptomatic infection (adjusted HR 2.88, 1.4 to 4.5) and for TFI age <20 versus >24 years at first infection (HR 4.35, 1.1 to 16.8). CONCLUSION: We found a considerably higher risk for PID and TFI in chlamydia-positive women, but the incidence for ectopic pregnancy was comparable between chlamydia-positive and chlamydia-negative women. Overall, the incidence rates of sequelae remained low. TRIAL REGISTRATION: NTR-5597.

Stable Low Hepatitis C Virus Antibody Prevalence Among HIV-Negative Men Who Have Sex With Men Attending the Sexually Transmitted Infection Outpatient Clinic in Amsterdam, 2007 to 2017.

BACKGROUND: In response to the increased hepatitis C virus (HCV) prevalence recently found among participants of the Amsterdam preexposure prophylaxis demonstration project, we evaluated HCV prevalence over time and the performance of the HCV-MOSAIC risk score for detection of HCV infection in HIV-negative men who have sex with men (MSM) attending the Amsterdam sexually transmitted infection (STI) clinic. METHODS: In October 2016, HIV-negative MSM were tested for anti-HCV and HCV RNA and completed the HCV-MOSAIC risk score. Anti-HCV prevalence was compared with that found in cross-sectional studies at the Amsterdam STI clinic (2007-2017). The time trend in HCV prevalence was modeled via logistic regression. The performance of the HCV-MOSAIC risk score, adjusted to identify prevalent HCV infection, was evaluated by calculating sensitivity and specificity. RESULTS: Of 504 HIV-negative MSM tested in October 2016, 5 were anti-HCV positive (1.0%, 95% confidence interval [CI], 0.4%-2.3%) and all were HCV RNA negative. Sensitivity and specificity of the adjusted HCV-MOSAIC risk score for prevalent infection were 80.0% (95% CI, 37.6%-96.4%) and 56.1% (95% CI, 51.7%-60.4%), respectively. The overall anti-HCV prevalence among 3264 HIV-negative MSM participating in cross-sectional studies at the Amsterdam STI clinic (2007-2017) was 0.8% (95% CI, 0.5%-1.2%) and did not change over time (P = 0.55). CONCLUSIONS: Anti-HCV prevalence among HIV-negative MSM attending the Amsterdam STI clinic in October 2016 was 1.0% and remained stable over time. We would therefore not recommend routine HCV screening of HIV-negative MSM at the STI clinic. However, given the increased prevalence among MSM using preexposure prophylaxis, periodic monitoring of HCV prevalence remains important.

Men who have sex with men more often chose daily than event-driven use of pre-exposure prophylaxis: baseline analysis of a demonstration study in Amsterdam.

INTRODUCTION: The Amsterdam PrEP project is a prospective, open-label demonstration study at a large sexually transmitted infection (STI) clinic. We examined the uptake of PrEP; the baseline characteristics of men who have sex with men (MSM) and transgender persons initiating PrEP; their choices of daily versus event-driven PrEP and the determinants of these choices. METHODS: From August 2015 through May 2016, enrolment took place at the STI clinic of the Public Health Service of Amsterdam, the Netherlands. MSM or transgender persons were eligible if they had at least one risk factor for HIV infection within the preceding six months. Participants were offered a choice between daily or event-driven use of tenofovir/emtricitabine. Baseline data were analysed using descriptive statistics and multivariable analysis was employed to determine variables associated with daily versus event-driven PrEP. RESULTS: Online applications were submitted by 870 persons, of whom 587 were invited for a screening visit. Of them, 415 were screened for eligibility and 376 initiated PrEP. One quarter (103/376, 27%) chose event-driven PrEP. Prevalence of bacterial STI was 19.0% and mean condomless anal sex (CAS) episodes in the preceding three months were 11. In multivariable analysis, older age (≥45 vs. ≤34, aOR 2.1, 95% CI 1.2 to 3.9), being involved in a steady relationship (aOR 1.7, 95% CI 1.0 to 2.7), no other daily medication use (aOR 0.6, 95% CI 0.3 to 0.9), and fewer episodes of CAS (per log increase aOR 0.7, 95% CI 0.6 to 0.9) were determinants for choosing event-driven PrEP. DISCUSSION: PrEP programmes are becoming one of the more important intervention strategies with the goal of reducing incident HIV-infection and we were unable to accommodate many of the persons applying for this study. Offering a choice of dosing regimen to PrEP users may enable further personalization of HIV prevention strategies and enhance up-take, adherence and cost-effectiveness. CONCLUSIONS: The majority of participants preferred daily versus event-driven use. Within this majority, a high number of CAS episodes before PrEP initiation was reported and we observed a high prevalence of STI. Determinants of choosing event-driven PrEP were older age, fewer CAS episodes, no other daily medication use, and involved in a steady relationship.

The Acceptability of Pre-Exposure Prophylaxis: Beliefs of Health-Care Professionals Working in Sexually Transmitted Infections Clinics and HIV Treatment Centers.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV infections, but is not yet implemented in the Netherlands. As the attitudes of health-care professionals toward PrEP can influence future PrEP implementation, we studied PrEP knowledge and beliefs and their association with PrEP acceptability among professionals in clinics for sexually transmitted infection (STI professionals) and HIV treatment centers (HIV specialists). In addition, we examined preferred regimens, attitudes toward providing PrEP to key populations and to reimbursement of PrEP costs. METHODS: An online questionnaire was distributed among 24 public health STI clinics and 27 HIV treatment centers nationwide in the Netherlands between January and August 2015. The acceptability of PrEP was measured on a 7-point Likert scale ranging from 1 = low to 7 = high acceptability. Univariable and multivariable linear regression analyses were used to explore associations between demographic characteristics, PrEP knowledge, beliefs about PrEP, and PrEP acceptability. RESULTS: In total, 209 people (143 STI professionals and 66 HIV specialists) completed the questionnaire. The mean acceptability of PrEP implementation was 4.28 (SD 1.68) among STI professionals and 4.42 (SD 1.67) among HIV specialists. The mean score on self-perceived knowledge related to PrEP efficacy was 3.90 (SD 1.57) among STI professionals and 5.68 (SD 1.08) among HIV specialists (p-value of <0.001). Beliefs associated with lower PrEP acceptability among both groups were the fear that PrEP use will lead to a decrease in condom use and an increase in STI, the high costs of PrEP and ethical issues regarding prescribing antiretroviral medication to healthy individuals. No preference for a daily or an event-driven regimen was detected. Most participants deemed the following groups to be eligible for PrEP: men who have sex with men (MSM) who regularly get post-exposure prophylaxis, MSM who never used condoms with casual partners and MSM with an HIV-positive partner with a detectable viral load. Over half of the participants indicated that PrEP users should partly (54.1%) or fully (35.4%) pay the costs of PrEP. CONCLUSION: In 2015, PrEP acceptability was only moderate among Dutch STI professionals and HIV specialists, which is far from an optimal setting. Addressing barriers to PrEP acceptability in educational programs for various types of health-care professionals is needed to successfully implement PrEP in the Netherlands.

Determinants of Human Papillomavirus Vaccination Intention Among Female Sex Workers in Amsterdam, the Netherlands.

INTRODUCTION: Female sex workers (FSWs) are at risk for human papillomavirus (HPV)-induced diseases but are currently not targeted by the HPV vaccination program in the Netherlands. We explored determinants of their intention to get vaccinated against HPV in case vaccination would be offered to them. METHODS: In 2016, FSWs 18 years and older having a sexually transmitted infection consultation with the Prostitution & Health Center (P&G292) in Amsterdam, either at the clinic or at their working location, were invited to complete a questionnaire assessing sociopsychological determinants of HPV vaccination intention (scale ranging from -3 to +3). Determinants of HPV vaccination intention were assessed with univariable and multivariable linear regression. In addition, we explored the effect of out-of-pocket payment on intention. RESULTS: Between May and September 2016, 294 FSWs participated. The median age was 29 years (interquartile range, 25-37 years). Human papillomavirus vaccination intention was high (mean, 2.0; 95% confidence interval [CI], 1.8-2.2). In multivariable analysis, attitude (ß = 0.6; 95% CI, 0.5-0.7), descriptive norm (ß = 0.2; 95% CI, 0.1-0.3), self-efficacy (ß = 0.2; 95% CI, 0.1-0.3), beliefs (ß = 0.1; 95% CI, 0.0-0.2), and subjective norm (ß = 0.1; 95% CI, 0.0-0.2) seemed to be the strongest predictors of HPV vaccination intention (R = 0.54). Human papillomavirus vaccination intention decreased significantly to a mean of 0.2 when vaccination would require out-of-pocket payment of &OV0556;350. CONCLUSIONS: The HPV vaccination intention among FSWs seems relatively high and is most strongly constituted in attitudinal, normative, and self-efficacy beliefs. Out-of-pocket payment will probably have a negative impact on their HPV vaccination acceptability.

Development and validation of the HCV-MOSAIC risk score to assist testing for acute hepatitis C virus (HCV) infection in HIV-infected men who have sex with men (MSM).

Current guidelines recommend hepatitis C virus (HCV) testing for HIV-infected men who have sex with men (MSM) with ongoing risk behaviour, without specifying the type of risk behaviour. We developed and validated the HCV-MOSAIC risk score to assist HCV testing in HIV-infected MSM. The risk score consisted of six self-reported risk factors identified using multivariable logistic regression using data from the Dutch MOSAIC study (n = 213, 2009-2013). Area under the ROC curve (AUC), sensitivity, specificity, post-test-probability-of-disease and diagnostic gain were calculated. The risk score was validated in case-control studies from Belgium (n = 142, 2010-2013) and the United Kingdom (n = 190, 2003-2005) and in cross-sectional surveys at a Dutch sexually transmitted infections clinic (n = 284, 2007-2009). The AUC was 0.82; sensitivity 78.0% and specificity 78.6%. In the validation studies sensitivity ranged from 73.1% to 100% and specificity from 56.2% to 65.6%. The post-test-probability-of-disease ranged from 5.9% to 20.0% given acute HCV prevalence of 1.7% to 6.4%, yielding a diagnostic gain of 4.2% to 13.6%. The HCV-MOSAIC risk score can successfully identify HIV-infected MSM at risk for acute HCV infection. It could be a promising tool to improve HCV testing strategies in various settings.

MSM starting preexposure prophylaxis are at risk of hepatitis C virus infection.

OBJECTIVES AND DESIGN: Hepatitis C virus (HCV) has been recognized as an emerging sexually transmitted infection (STI) among HIV-positive MSM. However, HIV-negative MSM at high risk for HIV might also be at increased risk for HCV. We studied the HCV prevalence in HIV-negative MSM who start preexposure prophylaxis (PrEP) in Amsterdam. Phylogenetic analysis was used to compare HCV strains obtained from HIV-negative and HIV-positive MSM. METHODS: At enrolment in the Amsterdam PrEP demonstration project, HIV-negative MSM were tested for the presence of HCV antibodies and HCV RNA. If positive for HCV RNA, an HCV NS5B gene fragment (709 bp) was sequenced and compared with HCV isolates from HIV-positive MSM (n = 223) and risk groups other than MSM (n = 153), using phylogenetic analysis. RESULTS: Of 375 HIV-negative MSM enrolled in Amsterdam PrEP, 18 (4.8%, 95% confidence interval 2.9-7.5%) of participants were anti-HCV and/or HCV RNA positive at enrolment; 15 of 18 (83%) had detectable HCV RNA. HCV genotyping showed genotype 1a (73%), 4d (20%), and 2b (7%). All HCV-positive MSM starting PrEP were part of MSM-specific HCV clusters containing MSM with and without HIV. CONCLUSION: HCV prevalence among HIV-negative MSM who started PrEP was higher than previously reported. All HIV-negative HCV-positive MSM were infected with HCV strains already circulating among HIV-positive MSM. The increasing overlap between sexual networks of HIV-positive and HIV-negative MSM might result in an expanding HCV-epidemic irrespective of HIV-status. Hence, routine HCV testing should be offered to MSM at high risk for HIV, especially for those enrolling in PrEP programs.

Incidence of repeat testing and diagnoses of Chlamydia trachomatis and Neisseria gonorrhoea in swingers, homosexual and heterosexual men and women at two large Dutch STI clinics, 2006-2013.

OBJECTIVE: Swingers, that is, heterosexuals who as a couple have sex with others, including group sex and bisexual behaviour, are an older-aged risk group for STIs. Here, we report on their repeat testing (reattendance) and STI yield compared with other heterosexuals and men who have sex with men (MSM, homosexual men) at two Dutch STI clinics. METHODS: Swingers are routinely (since 2006, South Limburg, registration-completeness: 99%) or partially (since 2010, Amsterdam, registration-completeness: 20%) included in the clinic patient registries. Data (retrospective cohort) are analysed to assess incidence (per 100 person-years (PY)) of reattendance and STI (Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG)) and associated factors calculating HRs. RESULTS: In South Limburg 7714 and in Amsterdam 2070 swinger consultations were identified. Since 2010, swingers' incidence of reattendance was 48-57/100 PY. Incidence was lower in MSM (30-39/100 PY, HR 0.56; 95% CI 0.51 to 0.61, South Limburg; HR 0.88; 95% CI 0.80 to 0.96, Amsterdam), heterosexual men (8-14/100 PY, HR 0.16; 95% CI 0.15 to 0.17, South Limburg; HR 0.33; 95% CI 0.30 to 0.36, Amsterdam) and women (13-20/100 PY, HR 0.56; 95% CI 0.51 to 0.61, South Limburg; HR 0.46; 95% CI 0.42 to 0.51, Amsterdam). Swingers' STI incidence at reattendance was 11-12/100 PY. Incidence was similar in heterosexual men (14-15/100 PY; HR 1.19; 95% CI 0.90 to 1.57, South Limburg; HR 1.20; 95% CI 0.91 to 1.59, Amsterdam) and women (12-14/100 PY; HR 1.14; 95% CI 0.88 to 1.49, South Limburg; HR 0.98; 95% CI 0.74 to 1.29, Amsterdam) and higher in MSM (18-22/100 PY; HR 1.59; 95% CI 1.19 to 2.12, South Limburg; HR 1.80; 95% CI 1.36 to 2.37, Amsterdam). Risk factors for STI incidence were partner-notified (contact-tracing), symptoms and previous STI. Swingers' positivity at any clinic attendance was 3-4% for NG (ie, higher than other heterosexuals) and 6-8% for CT (ie, lower than heterosexuals overall but higher than older heterosexuals). CONCLUSIONS: Systematic identification reveals that swingers are part of the normal STI clinic populations. They frequently repeat test yet are likely under-recognised in clinics which not routinely ask about swinging. Given swingers' notable STI rates, usage of services is warranted, although use may be restricted, that is, to those with an STI risk factor (as did Dutch clinics). As swingers have dense sexual networks, enhancing contact-tracing may have high impact.

Frequency and determinants of consistent STI/HIV testing among men who have sex with men testing at STI outpatient clinics in the Netherlands: a longitudinal study.

OBJECTIVES: Men who have sex with men (MSM) are at highest risk for STIs and HIV infections in the Netherlands. However, official guidelines on STI testing among MSM are lacking. They are advised to test for STIs at least every six months, but their testing behaviour is not well known. This study aimed to get insight into the proportion and determinants of consistent 6-monthly STI testing among MSM testing at STI outpatient clinics in the Netherlands. METHODS: This study included longitudinal surveillance data of STI consultations among MSM from all 26 STI outpatient clinics in the Netherlands between 1 June 2014 and 31 December 2015. Multinomial logistic regression analysis was used to identify determinants of consistent 6-monthly testing compared with single testing and inconsistent testing. Determinants of time between consultations among men with multiple consultations were analysed using a Cox Prentice-Williams-Peterson gap-time model. RESULTS: A total of 34 605 STI consultations of 18 634 MSM were included. 8966 (48.1%) men had more than one consultation, and 3516 (18.9%) men tested consistently 6-monthly. Indicators of high sexual risk behaviour, including having a history of STI, being HIV positive and having more than 10 sex partners, were positively associated with both being a consistent tester and returning to the STI clinic sooner. Men who were notified by a partner or who reported STI symptoms were also more likely to return to the STI clinic sooner, but were less likely to be consistent testers, identifying a group of event-driven testers. CONCLUSIONS: The proportion of consistent 6-monthly testers among MSM visiting Dutch STI outpatient clinics was low. Testing behaviour was associated with sexual risk behaviour, but exact motives to test consistently remain unclear. Evidence-based testing guidelines are needed to achieve optimal reductions in STI transmission in the future.

Design of the FemCure study: prospective multicentre study on the transmission of genital and extra-genital Chlamydia trachomatis infections in women receiving routine care.

BACKGROUND: In women, anorectal infections with Chlamydia trachomatis (CT) are about as common as genital CT, yet the anorectal site remains largely untested in routine care. Anorectal CT frequently co-occurs with genital CT and may thus often be treated co-incidentally. Nevertheless, post-treatment detection of CT at both anatomic sites has been demonstrated. It is unknown whether anorectal CT may play a role in post-treatment transmission. This study, called FemCure, in women who receive routine treatment (either azithromycin or doxycycline) aims to understand the post-treatment transmission of anorectal CT infections, i.e., from their male sexual partner(s) and from and to the genital region of the same woman. The secondary objective is to evaluate other reasons for CT detection by nucleic acid amplification techniques (NAAT) such as treatment failure, in order to inform guidelines to optimize CT control. METHODS: A multicentre prospective cohort study (FemCure) is set up in which genital and/or anorectal CT positive women (n = 400) will be recruited at three large Dutch STI clinics located in South Limburg, Amsterdam and Rotterdam. The women self-collect anorectal and vaginal swabs before treatment, and at the end of weeks 1, 2, 4, 6, 8, 10, and 12. Samples are tested for presence of CT-DNA (by NAAT), load (by quantitative polymerase chain reaction -PCR), viability (by culture and viability PCR) and CT type (by multilocus sequence typing). Sexual exposure is assessed by online self-administered questionnaires and by testing samples for Y chromosomal DNA. Using logistic regression models, the impact of two key factors (i.e., sexual exposure and alternate anatomic site of infection) on detection of anorectal and genital CT will be assessed. DISCUSSION: The FemCure study will provide insight in the role of anorectal chlamydia infection in maintaining the CT burden in the context of treatment, and it will provide practical recommendations to reduce avoidable transmission. Implications will improve care strategies that take account of anorectal CT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02694497 .