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Introduction: Oral pre-exposure prophylaxis (PrEP) prevents Human Immunodeficiency Virus (HIV) acquisition. In the Netherlands, PrEP is accessible through the national PrEP program (NPP) or general practitioners (GP). Still, some men who have sex with men (MSM) entering HIV care indicated having PrEP experience prior to diagnosis. We aimed to identify barriers and missed opportunities in PrEP uptake, care and use among MSM with HIV and previous PrEP experience., Methods: Between March 2022-March 2023, we conducted semi-structured in-depth interviews on PrEP among MSM diagnosed with HIV from 2019 onwards with previous PrEP experience. Interviewees were recruited through their HIV treatment centers and social media., Results: Of the 11 included MSM, most reported significant PrEP-uptake delay because of the limited NPP capacity and high threshold of accessing PrEP from GPs (e.g. stigma, lack of sexual health expertise). Additional uptake or use barriers included anticipated/experienced side-effects, burden of daily pill-taking or event-driven regimen complexity, the latter leading to PrEP discontinuation. Missed opportunities in counseling on adherence and safer sex alternatives after discontinuation were reported. Most interviewees considered informal PrEP unsuitable., Conclusion: PrEP uptake delay played a crucial role in context of HIV infection among MSM with HIV and previous PrEP experience. HIV diagnoses at or shortly after PrEP initiation emphasize the importance of ensuring rapid and timely PrEP access. Uptake barriers at GPs, stigma on sexuality, lack of expertise, and missed care opportunities need to be addressed. Early detection of PrEP protocol/user-mismatch and counseling on safer sex alternatives after discontinuation are pivotal for sustainable HIV prevention., Competing Interests: MP obtained unrestricted research grants and speaker/advisory fees from Gilead Sciences, Abbie and MSD; all of which were paid to her institute and were unrelated to the current work. UD obtained unrestricted research grants and speaker fees from Gilead Science; this was paid to his institution and was unrelated to the current work. No potential conflicts of interests were reported by the remaining authors. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2025 Koole et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

BackgroundIn the Netherlands, HIV pre-exposure prophylaxis (PrEP) has been available since 2019. However, the extent of PrEP use prior to HIV diagnosis and development of PrEP-resistance-associated mutations (RAMs) is not known.AimWe assessed prior PrEP use and potential transmission of PrEP RAMs among men who have sex with men (MSM) and transgender persons (TGP) with a new HIV diagnosis in the Netherlands.MethodsData on prior PrEP use between 1 January 2018 and 31 December 2022 were available from the Dutch national ATHENA cohort. We assessed proportion of prior PrEP use, detected PrEP associated RAMs and assessed potential onward transmission of RAMs between 2010 and 2022 using a maximum likelihood tree.ResultsData on prior PrEP use were available for 583/1,552 (36.3%) individuals, with 16% (94/583) reporting prior PrEP use. In 489 individuals reporting no prior PrEP use, 51.5% did not use PrEP due to: low HIV-risk perception (29%), no access (19.1%), personal preference (13.1%), and being unaware of PrEP (19.1%). For PrEP users, 13/94 (13.8%) harboured a M184V/I mutation, of whom two also harboured a K65R mutation. In people with a recent HIV infection, detection of PrEP RAMs increased from 0.23% (2/862) before 2019 to 4.11% (9/219) from 2019. We found no evidence of onward transmission of PrEP RAMs.ConclusionThe prevalence of PrEP-associated RAMs has increased since PrEP became available in the Netherlands. More widespread access to PrEP and retaining people in PrEP programmes when still at substantial risk is crucial to preventing new HIV infections.

Background: Knowledge on genital type-specific human papillomavirus (HPV) prevalence among men is important for prevention of HPV-related cancers and other diseases. Men who have sex with men (MSM) have higher anal prevalence than men who have sex with women only (MSW) but for genital HPV this is unclear. We performed a systematic review and meta-analysis of type-specific genital HPV prevalence among men, by sexual orientation., Methods: MEDLINE and Embase were used for searching publications reporting on male genital HPV prevalence with data from November 2011 onwards. A random-effects meta-analysis was conducted estimating pooled type-specific and grouped external genital and urethral HPV prevalence. Subgroup analyses were conducted for sexual orientation., Results: Twenty-nine studies were eligible. Of those, 13 studies reported prevalence among MSM, 5 among MSW, and 13 studies did not stratify by sexual orientation. The most common genotypes were HPV-6 and HPV-16 for both anatomical locations, although heterogeneity was high. HPV prevalence was similar among studies reporting on MSW, MSM, and men with unknown sexual orientation., Conclusions: Genital HPV is common among men, with HPV-6 and HPV-16 being the most common genotypes. Type-specific HPV genital prevalence appears to be similar among MSM and MSW, which contrasts with earlier findings on anal HPV., Competing Interests: Potential conflicts of interest. M. S. V. D. L. reports that his institution receives research funding from GSK; and he served on advisory boards of MSD and Novosanis; all payments were made to his institution. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The COVID-19 pandemic has widespread consequences for health facilities, social contacts, and health-seeking behaviour, affecting the incidence, diagnosis and reporting of other infectious diseases. We examined trends in reported chronic hepatitis C virus (HCV) infections and associated transmission routes in the Netherlands to identify the potential impact of COVID-19 on access to healthcare (testing) services., Methods: We analysed notification data of patients with chronic HCV reported to the National Notifiable Disease Surveillance System from January 2019 until December 2021 in the Netherlands. Rates of newly reported chronic cases per 100,000 population with 95% confidence intervals (CI) were calculated, and we compared proportional changes in transmission routes for chronic HCV between 2019, 2020 and 2021., Results: During the study period, a total of 1,521 chronic HCV infections were reported, 72% males, median age 52 years, and an overall rate of 8.8 (95%CI 8.4-9.2) per 100,000 population. We observed an overall decline (-41.9%) in the number of reported chronic HCV in 2020 compared to 2019, with the sharpest decline in men who have sex with men (MSM)-related transmission (-57.9% in 2020, p = 0.005)., Conclusions: Reported cases of chronic HCV strongly declined during the COVID-19 pandemic when healthcare services were scaled down. Between February and June 2021, reported chronic HCV cases increased again, indicating a recovery of healthcare services. MSM showed the largest decline compared to other groups. Further research is needed to fully understand the impact of access to healthcare, health seeking behaviour, and (sexual) transmission risks of HCV during the COVID-19 pandemic., (© 2023. The Author(s).)

This study identified subgroups of sexual behaviors associated with increased STI/HIV risk among those eligible for but not using pre-exposure prophylaxis (PrEP) in order to improve PrEP uptake and prioritization in the context of restricted capacity. We used data from sexual health centers (SHCs) in the Netherlands, including all visits of eligible but non-PrEP using men who have sex with men (MSM), men who have sex with men and women (MSMW) and transgender persons between July 2019 (start of the Dutch national PrEP pilot (NPP)) and June 2021. Using latent class analysis (LCA), we identified classes of sexual behaviors (number of partners, chemsex, group sex and sex work) and explored whether these classes were associated with STI diagnosis and sociodemographics. Across 45,582 visits of 14,588 eligible non-PrEP using individuals, the best fitting LCA model contained three classes of sexual behaviors. Classes were distinguished by seldomly reported sexual behaviors (class 1; 53.5%, n = 24,383), the highest proportions of ≥6 partners and group sex (class 2; 29.8%, n = 13,596), and the highest proportions of chemsex and sex work (class 3; 16.7% of visits, n = 7,603). Visits in classes 2 and 3 (vs. class 1) were significantly more often with individuals who were diagnosed with an STI, older (≥36 vs. ≤35 years), MSMW (vs. MSM), and visiting an urban (vs. non-urban) SHC; while these visits were significantly less often with individuals from an STI/HIV endemic area. The percentage of visits at which an STI was diagnosed was 17.07% (n = 4,163) in class 1, 19.53% (n = 2,655) in class 2 and 25.25% (n = 1,920) in class 3. The highest risk of STI, and thereby HIV, was in those engaging in specific subgroups of sexual behavior characterized by frequently reporting multiple partners, group sex, sex work or chemsex. PrEP uptake should be encouraged and prioritized for these individuals., Competing Interests: MP obtained unrestricted research grants and speaker/ advisory fees from Gilead Sciences, Abbvie and MSD; all of which were paid to her institute and were unrelated to the current work. EH obtained unrestricted research grants from Gilead Sciences, which were paid to her institute and were unrelated to the current work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors report no conflicts of interest., (Copyright: © 2023 de la Court et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

Background: During the COVID-19 pandemic, the disruption in care for sexually transmitted infections (STIs) and the social distancing measures have led to reductions in STI testing and sexual behavior. We assessed the impact of these COVID-19-related changes on transmission of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among men who have sex with men (MSM) in The Netherlands., Methods: We developed a mathematical model for CT and NG transmission among MSM, accounting for COVID-19-related changes in sexual behavior and testing in 2020 to 2021. Changes in 2020 were estimated from data from the Dutch COVID-19, Sex, and Intimacy Survey among MSM and the National Database of STI Clinics. Because of the lack of data for 2021, we examined several scenarios covering a range of changes., Results: A reduction of 10% and 40% in STI testing of symptomatic and asymptomatic, respectively, individuals with a 10% to 20% reduction in numbers of casual partners (according to partner status and activity level) during the second lockdown, resulted in a 2.4% increase in CT prevalence, but a 2.8% decline in NG prevalence in 2021. A 5% and 30% reduction in STI testing of symptomatic and asymptomatic, respectively, individuals with the same reduction in casual partners resulted in a 0.6% increase in CT prevalence and a 4.9% decrease in NG prevalence in 2021., Conclusions: The disruption in STI care due to COVID-19 might have resulted in a small increase in CT prevalence, but a decrease in NG prevalence. Scaling up STI care is imperative to prevent increases in STI transmission., Competing Interests: Conflicts of Interest and Sources of Funding: None declared., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

This study aimed to assess whether educational level is an independent determinant for sexually transmitted infections (STIs) among clients consulting Dutch sexual health centres (SHCs). With data from the National STI surveillance database (2015-2017), generalized estimating equations corrected for (sexual) risk factors were used to estimate associations between educational level and chlamydia and gonorrhoea among women ( n = 146,020), heterosexual men ( n = 82,882) and men who have sex with men (MSM) ( n = 52,149) and syphilis and HIV among MSM. Compared to the highest educational level (bachelor/master), all lower educational levels were associated with gonorrhoea among women (adjusted odds ratio 1.40; 95% CI 1.18-1.66 for higher general/pre-university level to 3.57; 95% CI 2.66-4.81 for no education/elementary school level) and heterosexual men (respectively 1.36; 1.06-1.74 to 3.84; 2.89-5.09). Women with no education/elementary school level (1.37; 1.17-1.62) and heterosexual clients with (pre-)vocational secondary educational level were more likely to test positive for chlamydia (women: 1.43; 1.39-1.48 and heterosexual men: 1.31; 1.26-1.37) than clients with higher general/pre-university level or bachelor/master level. In MSM, (pre-)vocational secondary educational level was associated with chlamydia (1.16; 1.11-1.22), gonorrhoea (1.15; 1.10-1.21) and syphilis (1.18; 1.08-1.29), and both (pre-)vocational secondary educational level (1.48; 1.25-1.76) and no education/elementary school level (1.81; 1.09-3.00) were associated with HIV. Lower educational levels were independent determinants of STI in SHC clients. Sexual health centres could facilitate STI testing and care among lower educated people by prioritizing their access.

Introduction: Surveillance for recent HIV infections was implemented at Dutch sexual health centres (SHCs) for planning and evaluation of HIV prevention initiatives. The study objective is twofold: (1) to explore trends in recent HIV infections and associated socio-demographic and behavioural risk factors among men who have sex with men (MSM )attending SHCs, to gain insight into subgroups at risk for acquiring HIV and(2) to illustrate how comparison with different reference groups affect associations with these risk factors., Methods: Residual plasma or serum samples from MSM newly HIV diagnosed at SHCs in 2014-2017 were tested with an avidity assay. Multinomial regression was used to analyse risk factors for recent HIV infections among MSM with established HIV infections among MSM and with HIV-negative MSM as reference groups., Results: Of newly diagnosed MSM, 33% were classified as recent HIV infection with avidity testing. Combining HIV-negative test results with avidity outcomes resulted in 54% recent infections. Recent infection was associated with having an STI in the past, multiple partners and condom use for both reference groups of MSM. Additionally, relative to the HIV-negative MSM, recent infection was associated with education and having a non-Western origin. In contrast, relative to MSM with established HIV infections, recent infection was associated with Western origin., Conclusion: Our results suggest ongoing but declining transmission of HIV and high uptake of HIV testing among MSM visiting SHCs. The identification of risk factors for recent infections can help healthcare professionals to target subgroups eligible for PrEP or condom use promotion. Differentiation by the reference group in explanatory models for recent infections is important as different risk factors were identified. Likely, associations relative to HIV-negative MSM follow those of acquiring HIV infection in general, whereas the comparison with the established HIV infection reference rather reflects the frequent testing behaviour of subgroups of MSM.

Objectives: To assess the cost-effectiveness of a preexposure prophylaxis (PrEP) programme offering a choice of daily and event-driven PrEP for men who have sex with men (MSM) in the Netherlands., Methods: We used an agent-based transmission model and an economic model to simulate a programme offering only daily PrEP and a programme offering daily and event-driven PrEP. Use of PrEP medication and preference for daily versus event-driven PrEP were estimated from the Amsterdam PrEP Demonstration Project (AMPrEP). We calculated costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICER), over 2018-2027. An ICER less than €20 000 per QALY gained was considered cost-effective., Results: Using AMPrEP data, we estimated that 27% of PrEP users chose event-driven PrEP with a median of 12 pills per month; daily PrEP users used a median of 30 pills per month. With PrEP, 3740 HIV infections were averted and 1482 QALYs were gained over 2018-2027, compared to the scenario without PrEP. The probability of the PrEP programme being cost-effective (compared to not having a PrEP programme) increased from 91% with daily PrEP to 94% with a choice of daily and event-driven PrEP. The probability of being cost-saving increased from 42% with only daily PrEP to 48% with choice of daily and event-driven PrEP., Conclusions: A daily PrEP programme for MSM would be cost-effective. Providing a choice of daily and event-driven PrEP can result in savings and is more likely to be cost-effective and cost-saving, compared to a programme offering only daily PrEP., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Risk-group HBV vaccination for men who have sex with men (MSM) was introduced in the Netherlands in 2002, followed by universal infant vaccination in 2011, that will enable termination of risk-group vaccination over time. The introduction of pre-exposure prophylaxis (PrEP) for HIV prevention might result in increased HBV testing and vaccination against HBV. The aim of this study was to investigate the impact of the transition from risk-group to universal HBV vaccination, accounting for improvements in HBV testing and treatment, as well as the introduction of PrEP., Methods: We developed a mathematical model for HBV transmission among MSM. Universal vaccination was modelled by assigning some MSM (5-15% in 2028 increasing to 80-90% in 2033 and thereafter) to be vaccinated when they become sexually active. We investigated different scenarios assuming 0.5% extra vaccination rate and 0.5% extra testing rate due to PrEP consultations; and 5% of HIV-negative MSM on PrEP, that will reduce the probability of HBV acquisition by 88%., Results: Universal vaccination resulted in a reduction of 24% (interquartile range; 22-25%) of the total number of HBV infections among MSM estimated to occur from 2020 to 2070. With universal vaccination, terminating risk-group vaccination in 2030 or 2040 resulted in 30% or 10% more HBV infections over 2020-2070, respectively, compared to continuation of risk-group vaccination until 2070. With PrEP and continued risk-group vaccination, the total number of HBV infections over 2020-2070 was reduced by 13%., Conclusions: Universal HBV vaccination can lead to a major reduction in HBV incidence among MSM in the future. The reduction becomes smaller when ending risk-group HBV vaccination, but larger by PrEP use for HIV prevention. Efforts to keep high levels of HBV vaccination, testing, and treatment have to be continued in the coming decades in order to eliminate HBV as a health threat for MSM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the impact and efficiency of combined testing for HIV and other STIs on HIV and STI transmission among men who have sex with men (MSM) and to assess what subgroups of MSM should be targeted for frequent testing., Methods: We developed an agent-based transmission model that simulates infection with HIV or Neisseria gonorrhoeae (NG) among MSM. We examined scenarios with increased percentages of MSM getting tested six monthly, among all MSM or only specific subgroups of MSM (defined according to recent gonorrhoea, number of partners and engagement in condomless anal intercourse (CAI)) and scenarios with reduced intervals between HIV/STI tests., Results: The most efficient strategies were those with increased percentage of MSM getting tested every 6 months among MSM with a recent gonorrhoea diagnosis; or among MSM who had CAI and ≥10 partners; or MSM who had ≥10 partners. Over 10 years, these strategies resulted in 387-718 averted HIV infections and required 29-164 additional HIV tests per averted HIV infection or one to seven additional gonorrhoea tests per averted NG infection. The most effective strategy in reducing HIV transmission was the one where the intervals between tests were reduced by half, followed by the strategy with increased percentage of MSM getting tested every 6 months among all MSM. Over 10 years, these strategies resulted in 1362 and 1319 averted HIV infections, but required 663 and 584 additional HIV tests per averted HIV infection, respectively., Conclusions: Targeting MSM with recent gonorrhoea diagnosis or MSM with many partners is efficient in terms of HIV/STI tests needed to prevent new HIV or NG infections. Major reductions in HIV incidence can be achieved with consistent HIV/STI testing every 6 months among larger groups, including low-risk MSM. To impede HIV transmission, frequent testing should be combined with other prevention measures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess the impact of a preexposure prophylaxis (PrEP) programme for high-risk men who have sex with men (MSM), which includes gonorrhoea testing and treatment, on the transmission of HIV and Neisseria among MSM in the Netherlands and the cost-effectiveness of such programme with and without risk compensation (in the form of reduced condom use)., Methods: We developed a stochastic agent-based transmission model of HIV and gonorrhoea. We simulated a capped (max 2.5% of MSM) and uncapped (5.5% of MSM in 2018 declining to 3% in 2027) daily PrEP programme for high-risk MSM, with 3-monthly HIV and gonorrhoea testing, with and without risk compensation. Epidemiological outcomes were calculated from the transmission model and used in an economic model to calculate costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICER), over 2018-2027, taking a healthcare payer perspective., Results: Without risk compensation, PrEP can lead to a reduction of 61 or 49% in the total number of new HIV infections in 2018-2027, if the programme is uncapped or capped to 2.5% of MSM, respectively. With risk compensation, this reduction can be 63 or 46% in the uncapped and capped programmes, respectively. In all scenarios, gonorrhoea prevalence decreased after introducing PrEP. Without risk compensation, 92% of simulations were cost-effective (of which 52% cost-saving). With risk compensation, 73% of simulations were cost-effective (of which 23% was cost-saving)., Conclusion: A nationwide PrEP programme for high-risk MSM can result in substantial reductions in HIV and gonorrhoea transmission and be cost-effective, even with risk compensation.

BackgroundWith regards to the global strategy towards eliminating viral hepatitis, reliable surveillance systems are essential to assess the national response for eliminating hepatitis C virus (HCV).AimWe aimed to assess the completeness of the two national registries with data on acute HCV infection in people with HIV, and estimated the number of acute HCV infections among adults (aged ≥ 18 years) with HIV in the Netherlands.MethodsIn this observational study, cases of HCV infection and reinfection among adults with a positive or unknown HIV-serostatus were identified from 2003 to 2016 in two national registries: the ATHENA cohort and the National Registry for Notifiable Diseases. For 2013-2016, cases were linked, and two-way capture-recapture analysis was carried out.ResultsDuring 2013-2016, there were an estimated 282 (95% confidence interval (CI): 264-301) acute HCV infections among adults with HIV. The addition of cases with an unknown HIV-serostatus increased the matches (from n = 107 to n = 129), and subsequently increased the estimated total: 330 (95%CI: 309-351). Under-reporting was estimated at 14-20%.ConclusionUnder-reporting of acute HCV infection among people with HIV could partially be explained by an unknown HIV-serostatus, or by differences in HCV stage (acute or chronic) at first diagnosis. Surveillance data should ideally include both acute and chronic HCV infections, and enable to distinguish these as well as initial- and re-infections. National surveillance of acute HCV can be improved by increased notification of infections.

Objectives: To assess the cost-effectiveness of increased consistent HIV testing among MSM in the Netherlands., Methods: Among MSM testing at sexually transmitted infection clinics in the Netherlands in 2014-2015, approximately 20% tested consistently every 6 months. We examined four scenarios with increased percentage of MSM testing every 6 months: a small and a moderate increase among all MSM; a small and a moderate increase only among MSM with at least 10 partners in the preceding 6 months. We used an agent-based model to calculate numbers of HIV infections and AIDS cases prevented with increased HIV testing. These numbers were used in an economic model to calculate costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) due to increased testing, over 2018-2027, taking a healthcare payer perspective., Results: A small increase in the percentage testing every 6 months among all MSM resulted in 490 averted HIV infections and an average ICER of &OV0556;27 900/QALY gained. A moderate increase among all MSM, resulted in 1380 averted HIV infections and an average ICER of &OV0556;36 700/QALY gained. Both were not cost-effective, with a &OV0556;20 000 willingness-to-pay threshold. Increasing the percentage testing every 6 months only among MSM with at least 10 partners in the preceding 6 months resulted in less averted HIV infections than increased testing among all MSM, but was on average cost-saving., Conclusion: Increased HIV testing can prevent considerable numbers of new HIV infections among MSM, but may be cost-effective only if targeted at high-risk individuals, such as those with many partners.

Background: In 2014 the World Health Organisation (WHO) established validation criteria for elimination of mother-to-child transmission (EMTCT) of HIV and syphilis. Additionally, the WHO set targets to eliminate hepatitis, including hepatitis B (HBV). We evaluated to what extent the Netherlands has achieved the combined WHO criteria for EMTCT of HIV, syphilis and HBV., Methods: Data of HIV, syphilis and HBV infections among pregnant women and children (born in the Netherlands with congenital infection) for 2009-2015, and data required to validate the WHO criteria were collected from multiple sources: the antenatal screening registry, the HIV monitoring foundation database, the Perinatal Registry of the Netherlands, the national reference laboratory for congenital syphilis, and national HBV notification data., Results: Screening coverage among pregnant women was > 99% for all years, and prevalence of HIV, syphilis and HBV was very low. In 2015, prevalence of HIV, syphilis and HBV was 0.06, 0.06 and 0.29%, respectively. No infections among children born in the Netherlands were reported in 2015 for all three diseases, and in previous years only sporadic cases were observed In 2015, treatment of HIV positive pregnant women was 100% and HBV vaccination of children from HBV positive mothers was > 99%. For syphilis, comprehensive data was lacking to validate WHO criteria., Conclusions: In the Netherlands, prevalence of maternal HIV, syphilis and HBV is low and congenital infections are extremely rare. All minimum WHO criteria for validation of EMTCT are met for HIV and HBV, but for syphilis more data are needed to prove elimination.

Objectives: Early testing for HIV and entry into care are crucial to optimise treatment outcomes of HIV-infected patients and to prevent spread of HIV. We examined risk factors for presentation with late or advanced disease in HIV-infected patients in the Netherlands., Methods: HIV-infected patients registered in care between January 1996 and June 2014 were selected from the ATHENA national observational HIV cohort. Risk factors for late presentation and advanced disease were analysed by multivariable logistic regression. Furthermore, geographical differences and time trends were examined., Results: Of 20,965 patients, 53% presented with late-stage HIV infection, and 35% had advanced disease. Late presentation decreased from 62% (1996) to 42% (2013), while advanced disease decreased from 46% to 26%. Late presentation only declined significantly among men having sex with men (MSM; p <0.001), but not among heterosexual males (p=0.08) and females (p=0.73). Factors associated with late presentation were: heterosexual male (adjusted OR (aOR), 1.59; 95% CI 1.44 to 1.75 vs MSM), injecting drug use (2.00; CI 1.69 to 2.38), age ≥ 50 years (1.46; CI 1.33 to 1.60 vs 30-49 years), region of origin (South-East Asia 2.14; 1.80 to 2.54, sub-Saharan Africa 2.11; 1.88 to 2.36, Surinam 1.59; 1.37 to 1.84, Caribbean 1.31; 1.13 to 1.53, Latin America 1.23; 1.04 to 1.46 vs the Netherlands), and location of HIV diagnosis (hospital 3.27; 2.94 to 3.63, general practitioner 1.66; 1.50 to 1.83, antenatal screening 1.76; 1.38 to 2.34 vs sexually transmitted infection clinic). No association was found for socioeconomic status or level of urbanisation. Compared with Amsterdam, 2 regions had higher adjusted odds and 2 regions had lower odds of late presentation. Results were highly similar for advanced disease., Conclusions: Although the overall rate of late presentation is declining in the Netherlands, targeted programmes to reduce late HIV diagnoses remain needed for all risk groups, but should be prioritised for heterosexual males, migrant populations, people aged ≥ 50 years and certain regions in the Netherlands., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: HIV-1 infection is characterized by chronic generalized CD8 and CD4 T cell hyperactivation, the biological effect of which is not understood., Objective: To study the relation between chronic immune activation and CD4 T cell depletion in HIV-1 infection., Design: Prospective cohort study among participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who have a known seroconversion date (n = 102)., Methods: CD4 and CD8 T cell activation marker expression was analysed by FACScan before and after seroconversion (1 and 5 years after seroconversion); T cell proliferation and T cell numbers were also measured. Cox proportional hazard analyses were used to study the predictive value of these parameters for progression to AIDS., Results: Preseroconversion low CD4 T cell numbers or elevated levels of CD4 T cell activation were associated with increased risk for development of AIDS after HIV-1 seroconversion. Progression to AIDS was associated with loss of both CD4 and CD8 naive T cells. The predictive value of CD8 T cell activation was confirmed and, in addition, in the course of infection low CD4 T cell counts and increasing proportions of dividing CD4 T cells, dividing CD8 T cells or elevated CD4 T cell activation marker expression became independent predictors of progression to AIDS., Conclusions: Increased T cell activation has predictive value for HIV-1 disease progression even before seroconversion. These data support the hypothesis that persistent hyperactivation of the immune system may lead to erosion of the naive T cell pool and CD4 T cell depletion.

HIV-1 infection is established by CCR5-utilizing (R5) variants, and CXCR4-utilizing (X4) variants emerge in approximately 50% of infected patients. We studied the role of CCR5 and CXCR4 expression before and 1 and 5 years after seroconversion in HIV-1 disease in a prospective study of 102 seroconverters. High percentages of CCR5(+) cells among total cells (relative hazard [RH], 2.55; 95% confidence interval [95% CI], 0.99-6.52), but not among CD45RO(-)CD4(+) and CD45RO(+)CD4(+) cells preseroconversion and among total cells and CD45RO(-)CD4(+) cells (RH, 2.70; 95% CI, 1.06-6.92 and RH, 3.54; 95% CI, 1.27-9.90, respectively) 5 years after seroconversion were associated with more rapid progression to AIDS. One year after seroconversion, high percentages of CXCR4(+) cells among total and CD45RO(-)CD4(+) cells were associated with delayed development of X4 variants (RH, 0.49; 95% CI, 0.20-1.21 and RH, 0.41; 95% CI, 0.17-1.02, respectively), whereas no association was observed for the percentage of CCR5(+) cells. In a larger study population, high early serum viral RNA and low CD4(+) T cell numbers were associated with more rapid development of X4 variants. Our results exclude target cell availability as a driving force for R5-to-X4 virus phenotype evolution.

Objectives: To determine indirectly the effect of changes in levels of reproductive hormones on CD4 lymphocyte counts by investigating the impact of pregnancy and menopause on CD4 lymphocyte counts in HIV-infected women., Methods: Participants were 382 women with a known interval of HIV seroconversion. Review of questionnaires or patient charts provided information on pregnancy and menopause. A linear regression model with a random intercept and slope, which adjusts for multiple CD4 lymphocyte counts per woman, was applied to estimate the CD4 decline following HIV seroconversion and to evaluate the effect of pregnancy and menopause on the CD4 path., Results: The 382 women had a median age of 25 years at seroconversion and yielded 1428 CD4 lymphocyte counts from 3 to 10 years after seroconversion. At 3 years from seroconversion, 20 women had passed the menopause (i.e., the last menses) and five more subsequently passed this point during follow-up; 25 women had a pregnancy after study entry. Postmenopausal women had lower CD4 lymphocyte counts 3 years after seroconversion than premenopausal women (333 vs 399 x 106 cells/l; P = 0.09), and pregnant women had lower counts than non-pregnant women (375 vs 399 x 106 cells/l; P = 0.36). The monthly CD4 decline was not associated with pregnancy and menopause. Adjustment for age did not change the results., Conclusions: The results suggest that CD4 lymphocyte counts differ between pre- and postmenopausal women, perhaps because of changes in the level of reproductive hormones in the menopause, but associations were not statistically significant. Pregnancy had no statistically significant effect on CD4 lymphocyte counts.

CD1d-restricted NKT cells express an invariant TCR and have been demonstrated to play an important regulatory role in a variety of immune responses. Invariant NKT cells down-regulate autoimmune responses by production of type 2 cytokines and can initiate antitumor and antimicrobial immune responses by production of type 1 cytokines. Although defects in the (invariant) Valpha24+Vbeta11+ NKT cell population have been observed in patients with cancer and autoimmune diseases, little is known regarding the protective role of Valpha24+Vbeta11+ NKT cells in human infectious disease. In a cross-sectional study in HIV-1-infected individuals, we found circulating numbers of Valpha24+Vbeta11+ NKT cells to be reduced, independent of CD4+ T cell counts, CD4:CD8 ratios, and viral load. Because a small minority of Valpha24+Vbeta11+ NKT cells of healthy donors expressed HIV-1 (co)receptors and the vast majority of Valpha24+Vbeta11+ NKT cells in HIV-1-infected individuals expressed the Fas receptor, the depletion was more likely due to Fas-mediated apoptosis than to preferential infection of Valpha24+Vbeta11+ NKT cells by HIV-1. A longitudinal cohort study, in which patients were analyzed before seroconversion and 1 and 5 years after seroconversion, demonstrated that a large proportion of the depletion occurred within the first year postseroconversion. In this longitudinal study no evidence was found to support an important role of Valpha24+Vbeta11+ NKT cells in determining the rate of progression during HIV-1 infection.