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Biomedical HIV-prevention strategies (BmPS) among men who have sex with men (MSM), such as pre-exposure prophylaxis (PrEP) and viral load sorting (VLS), are essential but relatively new and their uptake gradual. Using an extension of the causal attitude network approach, we investigated which beliefs are related to uptake of PrEP and VLS at each time-point. We included 632 HIV-negative MSM from the Amsterdam Cohort Studies from four data-waves between 2017 and 2019. We estimated weighted, undirected networks for each time-point, where we included pairwise interactions of PrEP and VLS uptake and related beliefs. PrEP use increased from 10 to 31% (p < 0.001), while VLS was reported by 7-10% at each time-point. Uptake of both BmPS was directly related to the perceived positive impact of the strategy on one's quality of sex life and perceived supportive social norms. Overall network structure differed between time points, specifically in regard to PrEP. At earlier time points, perceptions of efficacy and affordability played an important role for PrEP uptake, while more recently social and health-related concerns became increasingly important.The network structure differed across data-waves, suggesting specific time changes in uptake motives. These findings may be used in communication to increase prevention uptake., (© 2023. The Author(s).)

Men who have sex with men (MSM) initiating human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) may increase condomless anal sex (CAS) and number of partners, and, consequently, more often acquire sexually transmitted infections (STIs). Using data from the Amsterdam Cohort Studies, we compared sexual behavior and STI among MSM after PrEP-initiation with controls not initiating PrEP. The MSM reported on sexual behavior and were tested for HIV, chlamydia, gonorrhea, and syphilis semi-annually. We matched MSM who initiated PrEP between January 1, 2015 and December 31, 2019 1:1 to MSM who did not use time-dependent propensity scores based on age, sexual behavior, and STI. Primary end-points were number of casual partners, and proportion with CAS and receptive CAS (rCAS) with casual partners, sexualized drug use (SDU), any STI, and anal STI. We modeled end-points during the 4 years before and 2 years after PrEP-initiation or matched PrEP-initiation timepoint by using logistic regression (dichotomous end-points) or negative binomial regression (count end-point), adjusted for calendar year. Two hundred twenty-eight out of the 858 (26.6%) MSM initiated PrEP. We matched 198 out of 228 (86.8%) to a control. Before PrEP-initiation, end-points increased over time in both groups, with no statistically significant difference. The odds of CAS, rCAS, and anal STI were on average higher after than before PrEP-initiation in PrEP initiators, whereas after versus before differences were not observed in controls. After PrEP-initiation, PrEP initiators had statistically significantly more casual partners, and higher odds of CAS, rCAS, SDU, any STI, and anal STI than controls. These findings support frequent STI screening and counseling in MSM using PrEP.

Objectives: To assess differences in socio-demographics, HIV testing and healthcare seeking behavior between individuals diagnosed late and those diagnosed early after HIV-acquisition., Design: Cross-sectional study among recently HIV-diagnosed migrant and non-migrant individuals living in the Netherlands., Methods: Participants self-completed a questionnaire on socio-demographics, HIV-testing and healthcare seeking behavior preceding HIV diagnosis between 2013-2015. Using multivariable logistic regression, socio-demographic determinants of late diagnosis were explored. Variables on HIV-infection, testing and access to care preceding HIV diagnosis were compared between those diagnosed early and those diagnosed late using descriptive statistics., Results: We included 143 individuals with early and 101 with late diagnosis, of whom respectively 59/143 (41%) and 54/101 (53%) were migrants. Late diagnosis was significantly associated with older age and being heterosexual. Before HIV diagnosis, 89% of those with early and 62% of those with late diagnosis had ever been tested for HIV-infection (p<0.001), and respectively 99% and 97% reported healthcare usage in the Netherlands in the two years preceding HIV diagnosis (p = 0.79). Individuals diagnosed late most frequently visited a general practitioner (72%) or dentist (62%), and 20% had been hospitalized preceding diagnosis. In these settings, only in respectively 20%, 2%, and 6% HIV-testing was discussed., Conclusion: A large proportion of people diagnosed late had previously tested for HIV and had high levels of healthcare usage. For earlier-case finding of HIV it therefore seems feasible to successfully roll out interventions within the existing healthcare system. Simultaneously, efforts should be made to encourage future repeated or routine HIV testing among individuals whenever they undergo an HIV test., Competing Interests: The authors have declared that no competing interests exist.

Aims: To test whether recreational drug use (RDU) and sexualized drug use (SDU) changed in the Amsterdam area between 2008 and 2018 and quantify associations of SDU with condomless anal sex (CAS), recent human immunodeficiency virus (HIV) or sexually transmitted infections (STI) among human immunodeficiency virus (HIV)-negative men who have sex with men (MSM)., Design: Open prospective cohort study., Setting: Public Health Service of Amsterdam, the Netherlands., Participants: A total of 976 HIV-negative MSM, aged ≥ 18 years., Measurements: Self-reported RDU and sexual behaviour in the past 6 months. Laboratory-confirmed HIV and STI (chlamydia, gonorrhoea and syphilis). We studied: any RDU; any SDU (i.e. any RDU during sex); specific SDU (i.e. use of mephedrone, methamphetamine, gamma-hydroxybutyric acid/gamma-butyrolactone, ketamine, amphetamine, cocaine and/or ecstasy during sex); use of individual drugs; and use of individual drugs during sex. We evaluated changes over calendar years in the proportion of individuals with these end-points [using logistic regression with generalized estimating equations (GEE)] and number of drugs (using negative binomial regression with GEE), adjusted for current age, country of birth and education level., Findings: Median age of participants in 2008 was 33.2 years (interquartile range = 27.8-40.1); 83.1% were born in the Netherlands. The proportion of any RDU increased from 67.2% in 2008 to 69.5% in 2018 [adjusted odds ratio (aOR) = 1.25; 95% confidence interval (CI) = 1.03-1.51]. Any SDU increased from 53.8% in 2008 to 59.8% in 2013 (aOR = 1.23; 95% CI = 1.07-1.42) and remained stable afterwards. Specific SDU increased from 25.0% in 2008 to 36.1% in 2018 (aOR = 2.10; 95% CI = 1.71-2.58). The average number of drugs used increased for those reporting any RDU, any SDU and specific SDU (all P < 0.05. Among those engaging in sex, any SDU was associated with CAS (aOR = 1.36; 95% CI = 1.19-1.55), HIV (aOR = 5.86; 95% CI = 2.39-14.4) and STI (aOR = 2.31; 95% CI = 1.95-2.73). Specific SDU was associated with CAS (aOR = 1.58; 95% CI = 1.37-1.81), HIV (aOR = 6.30; 95% CI = 3.28-12.1) and STI (aOR = 2.15; 95% CI = 1.81-2.55)., Conclusions: Among human immunodeficiency virus (HIV)-negative men who have sex with men in Amsterdam, recreational drug use, including sexualized drug use, increased between 2008 and 2018. Sexualized drug use was strongly associated with condomless anal sex, HIV and sexually transmitted infections., (© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Men who have sex with men (MSM) are at increased risk of anogenital human papillomavirus (HPV) infections. We aimed to assess the incidence and clearance of penile high-risk HPV (hrHPV) infections and their determinants among HIV-negative MSM living in the Netherlands., Methods: Between 2010 and 2015, HIV-negative MSM were semiannually tested for penile HPV and completed detailed questionnaires on health and sexual behavior. Self-collected penile swabs were tested for HPV DNA using SPF10-PCR DEIA/LiPA25 system. Type-specific hrHPV incidence (IR) and clearance rates (CR) were calculated for 12 hrHPV types (HPV-16, HPV-18, HPV-31, HPV-33, HPV-35, HPV-39, HPV-45, HPV-51, HPV-52, HPV-56, HPV-58, and HPV-59). Determinants of incidence and clearance of HPV-16 and HPV-18, separately, and combined 7 hrHPV types covered by the nonavalent vaccine were assessed by Poisson regression using generalized estimating equations for combined hrHPV types., Results: We included 638 HIV-negative MSM, with a median age of 38 (interquartile range, 33-43) years. HPV-16 had an IR of 4.9/1000 person-months of observation at risk (PMO; 95% confidence interval [95% CI], 3.8-6.3) and CR of 90.6/1000 PMO (95% CI, 60.7-135.1). The IR and CR of HPV-18 were 3.4/1000 PMO (95% CI, 2.5-4.5) and 119.2/1000 PMO (95% CI, 76.9-184.8), respectively. Age and condom use during insertive anal sex were not associated with hrHPV incidence, whereas high number of recent sex partners was., Conclusions: The relatively high IR and low CR of penile HPV-16 and HPV-18 among HIV-negative MSM correlates with their high prevalence and oncogenic potential. Incident HPV infections were associated with recent sexual risk behavior., Competing Interests: Conflict of Interest and Sources of Funding: The institution of M.F.S.v.d.L. received study funding from Sanofi Pasteur MSD and Janssen Infectious Diseases and Vaccines; he was a coinvestigator in a Merck-funded investigator-initiated study; he was an investigator on a Sanofi Pasteur MSD–sponsored trial; he served on a vaccine advisory board of GSK; his institution received in-kind contribution for a human papillomavirus study from Stichting Pathologie Onderzoek en Ontwikkeling (SPOO). D.A.M.H. is a minority shareholder of Self-screen B.V., a spin-off company of VUmc. Self-screen B.V. holds patents related to the work, and develops, manufactures, and licenses a high-risk human papillomavirus assay and methylation marker assays. D.A.M.H. has served on the speaker's bureau of QIAGEN and occasionally on the scientific advisory boards of Pfizer and Bristol-Myers Squibb., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

To assess whether HIV-negative men who have sex with men (MSM) have realistic views of the current implications of living with HIV, we compared data of 950 tested HIV-negative and 122 never-tested MSM on anticipated consequences of an HIV-infection to the actual experiences of 438 MSM living with HIV. Data were collected with a self-reported, web-based survey conducted between May-June 2019 in the Netherlands. Results indicated that, compared to HIV-positive MSM, HIV-negative MSM significantly overestimated 95% (37/39) of items assessing HIV-related burden. Never-tested participants overestimated 85% (33/39) of items. Overestimation in never-tested MSM was modified with increasing age and having HIV-positive friends/relatives. The high level of overestimation suggests the ongoing need to correct for misperceptions, as this could help reduce stigma towards those living with HIV and diminish fear of an HIV-diagnosis. The latter might be important to improve testing uptake in older never-tested MSM with outdated views on HIV., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Men who have sex with men (MSM) and who are unaware of their HIV infection contribute to onward HIV transmission and are more likely to progress to severe illness. We therefore assessed determinants of never testing for HIV among MSM living in the Netherlands. Between April and July 2019, 950 HIV-negative and 122 never-tested MSM completed a cross-sectional survey on sociodemographics, HIV testing behavior, and sexual risk taking, which was distributed through gay networking sites/apps. In never-tested MSM, median age was 37 (interquartile range = 22-51) years and 37 (30%) reported recent sexual risk behavior. Never testing was associated with younger age [adjusted odds ratio (aOR) per year increase = 0.98, 95% confidence interval (CI) = 0.97-1.00, p  = 0.015], having sex with men and women (aOR = 2.85, 95% CI = 1.57-5.62, p  = 0.001), and not knowing others living with HIV (aOR = 3.85, 95% CI = 2.35-6.32, p  < 0.001) in multi-variable logistic regression analysis. A significant interaction effect between education level and residential area was observed ( p  = 0.001). Among higher-educated MSM, those living outside a large urban area had higher odds of never testing compared to those living in an urban area (aOR = 6.26, 95% CI = 2.42-16.24, p  < 0.001). Lower-educated MSM had higher odds of never testing irrespective of residential area (large urban area: aOR = 12.06, 95% CI = 4.00-36.38; outside large urban area: aOR 9.29, 95% CI = 3.64-23.76; p  < 0.001 for both). Among MSM recently exposed to sexual risk, never testing was associated with having sex with men and women (aOR = 2.80, 95% CI = 1.09-7.18, p  = 0.032) and not knowing others with HIV (aOR = 4.91, 95% CI = 1.97-12.24, p  = 0.001). To conclude, testing interventions for those never tested should be tailored to residential area and education level, and inclusive of bisexuality.

Background: Extended-spectrum β-lactamase Enterobacteriaceae (ESBL-E) may be sexually transmitted. Men who have sex with men (MSM) have different sexual behaviour than the general population, and thus may be at risk for ESBL-E carriage. This study determined the prevalence of ESBL-E carriage and its association with sexual behaviour among MSM in Amsterdam, The Netherlands., Materials and Methods: In total, 583 HIV-positive and HIV-negative MSM from the Amsterdam Cohort Study were screened for rectal ESBL-E carriage between April and December 2018. Participants completed a self-administered questionnaire on (sexual) behaviour and risk factors for antimicrobial resistance. The proportion of the study population with ESBL-E carriage was compared by number of sexual partners using logistic regression, and across clusters of sexual behaviours with steady and casual partners, separately, using latent class analyses; all results were adjusted for recent use of antibiotics, travel and hospitalization., Results: Overall, 16.3% [95% confidence interval (CI) 13.4-19.5] of the study population tested positive for ESBL-E. The odds of ESBL-E carriage increased as number of sexual partners increased [adjusted odds ratio per ln(partner+1), 1.57, 95% CI 1.26-1.94; P<0.001]. There was no association between ESBL-E carriage and sexual behaviour with steady partner(s). Compared with participants in the 'no sex with casual partner(s)' cluster, adjusted odds of being ESBL-E positive were 2.95-fold higher (95% CI 1.52-5.80) for participants in the 'rimming and frottage' cluster (P=0.001) and 2.28-fold higher (95% CI 0.98-5.31) for participants in the 'toy use and fisting' cluster (P=0.056)., Conclusions: The prevalence of ESBL-E in MSM is higher compared with the overall Dutch population, likely due to sexual transmission with casual partners. This implies that sexually active MSM should be considered a risk group for ESBL-E carriage., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To investigate the impact of Dutch COVID-19 restrictions on sexual behavior and HIV/sexually transmitted infection (STI) acquisition among men who have sex with men (MSM) participating in the Amsterdam Cohort Studies (ACS) on HIV in Amsterdam., Methods: ACS participants complete a questionnaire on sexual behavior and are tested for HIV/STI biannually. They may also be tested at the STI clinic in-between study visits. On May 29, 2020, ACS participants were invited to complete an online questionnaire on health, COVID-19 risk perceptions, and sexual behavior. Determinants of reporting casual sex partners (CSP) during COVID-19 restrictions were examined using logistic regression., Results: Of 683 MSM, 353 (52%; median age, 47 years; interquartile range, 38-53 years) completed the questionnaire. Since COVID-19, 73% reported a reduction in the number of CSP. CSP during COVID-19 restrictions were reported by 133 MSM (38%) and, in multivariable analysis, was associated with not having a college/university degree, being single, lower perceived importance of avoiding COVID-19, number of CSP before COVID-19, and current preexposure prophylaxis use (P < 0.05 for all). During COVID-19 restrictions, no HIV infections were diagnosed, and the STI positivity rate was 8%., Conclusion: Since COVID-19, the number of CSP decreased among MSM, and there may have been a temporary reduction in HIV/STI transmission. Some MSM were not fully compliant to social distancing regulations and reported CSP, which was related to prior sexual behavior and low perceived importance of avoiding COVID-19. For these men, it is important to maintain accessible HIV/STI-related testing and care during times of lockdown., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We aimed to investigate the motives, barriers and experiences of HIV-STAR study participants. The HIV-STAR study was an analytical HIV treatment interruption trial (ATI) aiming to evaluate the origin of viral rebound, conducted in Ghent, Belgium., Methods: A mixed-method study was performed among 11 participants of the HIV-STAR study. Two self-administered questionnaires with 32 and 23 items, respectively, assessed motives, barriers and experiences of the research participants. In-depth interviews were conducted to further explore and understand topics that had emerged from these surveys., Results: Motives of ATI study participants were primarily related to the improvement of their own health perspectives and to their contribution to find an HIV cure. Barriers for ATI participation mostly related to practical issues, such as difficulty in planning study visits. Ten out of 11 participants reported a very high overall satisfaction and were willing to participate in another ATI. This satisfaction was predominantly linked to clear communication and guidance. Invasive sampling during the ATI was less of a burden than anticipated by participants. However, most participants underestimated the emotional impact of HIV treatment interruption, which was associated with feelings of uncertainty and loss of control. Risk of HIV transmission because of viral rebound was also mentioned as burdensome during this phase., Conclusions: Involvement in an ATI was positively evaluated by HIV-STAR participants. Contributing to HIV cure research outweighed the burden of study participation for most participants. The latter aspects were attenuated by mutual decision making and the experience of empathy from the research team. Still, issues regarding privacy and the psychosocial impact of treatment interruption, including sexuality and HIV transmissibility, should be addressed in a better way., Competing Interests: 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., (© 2021 The Author(s).)

Background: With biomedical developments in treatment and prevention of HIV, the implications of living with HIV are considerably more manageable. Within this context, we aimed to describe and quantify the present-day burden of living with HIV among men who have sex with men (MSM) in the Netherlands., Methods: In this mixed-methods study, we did in-depth interviews on HIV-related burden with MSM diagnosed with HIV between 2014 and 2018. Interviewees were recruited at three HIV treatment centres and the Public Health Service of Amsterdam in the Netherlands. Using the transcripts from all interviewees, the qualitative analysis was done by two independent researchers applying an open-coding process. Results were used to generate a questionnaire measuring HIV-related burden, which was distributed via gay dating apps or sites and social media. MSM diagnosed with HIV before 2019 who completed the questionnaire were included in the quantitative analyses. Descriptive analyses were used to report burden prevalence and to explore differences in burden among MSM diagnosed at different antiretroviral therapy periods. Sociodemographic determinants of burden were explored using multinomial logistic regression., Findings: Between May, 2018, and March, 2019, 18 of 25 MSM who consented for further contact were interviewed, after which thematic saturation was reached. The interviewees revealed that aspects related to medicalisation and emotional consequences were burdensome temporarily after diagnosis, whereas aspects related to HIV status disclosure, stigma, and the sexual and social life were mentioned to be burdensome more persistently. Between April and July, 2019, 613 MSM with HIV started the quantitative survey, of whom 438 (71%) completed the questionnaire and were included in the analyses. These 438 MSM were diagnosed with HIV between 1984 and 2018. The median time since HIV diagnosis was 8 years (IQR 4-13). In total, 135 (31%) of 438 online respondents reported that living with HIV was generally experienced as burdensome and 361 (82%) would be relieved if HIV could be cured. Compared with a low level of burden, a moderate level of burden was associated with having another chronic condition (p=0·0030), and a high level of burden was associated with a more recent diagnosis (p=0·0060) and not knowing other individuals with HIV (p=0·0020). Disclosure dilemmas were reported to be the most burdensome, resulting in difficulties initiating sex (122 [32%] of 378 respondents) and establishing relationships (85 [41%] of 207 respondents). The most prevalent emotional consequences were shame (112 [26%] of 438 respondents) and stress (80 [18%] of 438 respondents). Disclosure and taking antiretroviral therapy in the presence of others were experienced as more burdensome among those diagnosed after 2005 than among those diagnosed in or before 2005., Interpretation: Our findings highlight that despite medical advancements, further stigma reduction programmes and adapted psychosocial support for specific profiles of MSM living with HIV are needed., Funding: HIV Transmission Elimination Amsterdam Initiative., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.

Background: Flat penile lesions (FPL) in heterosexual men are thought to play a role in the transmission of HPV. We investigated the association between FPL and penile HPV, and explored determinants of FPL in men who have sex with men (MSM)., Methods: In 2015-2016, MSM were recruited based on HIV and penile HPV status in a previous cohort. MSM self-completed a questionnaire. Peniscopy was performed after application of acetic acid to visualize FPL. Penile physician-collected samples were tested for HPV-DNA using the highly sensitive SPF10-PCR DEIA/LiPA25 system. HPV viral load (VL) was determined using a quantitative type-specific (q)PCR targeting the L1-region. Presence of HPV and HIV, HPV VL and circumcision status were compared between MSM with and without FPL., Results: We included 116 MSM, of whom 59/116 (51%) MSM were HIV-positive and 54/116 (47%) had FPL. A penile HPV infection was present in 31/54 (57%) MSM with FPL and 34/62 (55%) MSM without FPL (p = 0.8). There was no difference between MSM with and without FPL regarding presence of penile HPV infection, HPV VL, HIV status or circumcision status (p > 0.05 for all)., Conclusion: Among MSM in Amsterdam, we found no association between FPL and penile HPV, HPV VL, HIV status or circumcision status., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Deferral of men who have sex with men (MSM) from blood donation is highly debated. We therefore investigated their suitability to donate blood., Methods: We compared the antibody prevalence of 10 sexually and transfusion-transmissible infections (TTIs) among 583 MSM and 583 age-matched repeat male blood donors. MSM were classified as low risk (lr) or medium-to-high risk (hr) based on self-reported sexual behavior and as qualified or unqualified using Dutch donor deferral criteria. Infection pressure (IP) was defined as the number of antibody-reactive infections, with class A infections (human immunodeficiency virus-1/2, hepatitis B virus, hepatitis C virus, human T-cell lymphotropic virus-1/2, syphilis) given double weight compared to class B infections (cytomegalovirus, herpes simplex virus-1/2, human herpesvirus 8, hepatitis E virus, parvovirus B19)., Results: Donors had a lower median IP than qualified lr-MSM and qualified hr-MSM (2 [interquartile range {IQR}, 1-2] vs 3 [IQR, 2-4]; P < .001). Low IP was found in 76% of donors, 39% of qualified lr-MSM, and 27% of qualified hr-MSM. The prevalence of class A infections did not differ between donors and qualified lr-MSM but was significantly higher in qualified hr-MSM and unqualified MSM. Recently acquired class A infections were detected in hr-MSM only. Compared to blood donors, human herpesviruses were more prevalent in all MSM groups (P < .001)., Conclusions: IP correlates with self-reported risk behavior among MSM. Although lr-MSM might form a low threat for blood safety with regard to class A infections, the high seroprevalence of human herpesviruses in lr-MSM warrants further investigation., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: To investigate the incidence and risk factors of immune reconstitution inflammatory syndrome (IRIS) associated with toxoplasmic encephalitis (TE) in patients starting combination antiretroviral therapy (cART)., Design: A historical multicenter cohort study., Methods: We included all HIV-infected patients diagnosed with toxoplasmic encephalitis in six Dutch hospitals between 1996 and 2016. Diagnosis of TE-IRIS was made using predefined IRIS criteria. We distinguished paradoxical TE-IRIS (worsening of underlying treated infection) from unmasking TE-IRIS (unmasking of subclinical infection after start of cART). We compared CD4 cell count, plasma viral load and timing of cART initiation between patients with and without paradoxical TE-IRIS., Results: A total of 211 toxoplasmic encephalitis cases were included. Among 143 cases at risk for paradoxical TE-IRIS, we identified five cases of paradoxical TE-IRIS (3.5%). In six other cases, we could not differentiate paradoxical TE-IRIS from recurrence of disease due to inadequate secondary Toxoplasma prophylaxis. There was no difference in time between start of toxoplasmic encephalitis treatment and cART initiation for patients who did or did not develop paradoxical TE-IRIS (P = 0.50). Within the group of 2228 patients who started cART while having a CD4 cell count below 200 × 10 cells/l and receiving adequate primary prophylaxis, we identified eight cases of unmasking TE-IRIS (0.36%). Unmasking TE-IRIS could not be differentiated from a newly occurring toxoplasmic encephalitis in six other patients, as they were not receiving adequate primary prophylaxis against Toxoplasma., Conclusion: Unmasking TE-IRIS was rare in this cohort, whereas paradoxical TE-IRIS did occur more often. We found no relationship between the timing of cART initiation and the occurrence of paradoxical TE-IRIS.