The Best Predictor of Future Behavior May Be the Past: Exploring Behavior Change in Men Who Have Sex with Men Using Pre-exposure Prophylaxis in the Netherlands.

Pre-exposure prophylaxis (PrEP) use prevents HIV transmission, and may lead to changes in sexual behavior. We aimed to explore sexual behavior over time, and identify predictors of behavior change in men who have sex with men (MSM) using PrEP at sexual health centers (SHC) in the Netherlands. We used longitudinal data from the national STI surveillance database (January 2018-June 2021) of HIV-negative MSM who first initiated PrEP in the national PrEP pilot. We modelled behavior change after PrEP initiation, and identified predictors of behavior change using multi-state Markov models. The probability of stopping group sex, chemsex, use of poppers or erection stimulants, and having ≥ 10 partners in the past 6 months among included MSM (n = 4,349, n SHC visits = 21,820) was higher compared to the probability of starting with these behaviors after PrEP initiation. However, MSM who used condoms consistently during anal sex had a high probability of changing to inconsistent condom use (0.8) at the next visit, and inconsistent condom users mostly remained inconsistent (0.8). First visit, visiting the SHC more often (vs. regular), and STI diagnosis were predictors of starting or continuing with most of the behaviors associated with increased risk. Behavior change was less likely among older participants (> 34 compared to ≤ 34 years), and during COVID-19 lockdown and post-lockdown periods compared to pre-COVID-19. Although condom use decreased over time, transitions towards stopping with other behaviors associated with increased likelihood of acquiring an STI after PrEP initiation were common. This may suggest increased sexual empowerment, especially among younger MSM. Predictors of behavior change may help to identify MSM who are likely to start with or continue to engage in these behaviors in the near future and to provide suitable and timely counselling about behavior and PrEP adherence.

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

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

Concordance between daily diary reported pre-exposure prophylaxis intake and intraerythrocytic tenofovir diphosphate in the Amsterdam Pre-exposure Prophylaxis demonstration project.

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

Differences in STI/HIV Burden and Sexual Health Care-Seeking Behavior Among First- and Second-Generation Migrant and Western-Born Male Sex Workers Who Have Sex With Men in the Netherlands: A Retrospective Cohort Study.

BACKGROUND: Globally, migrant sex workers have a higher burden of sexually transmitted infections (STI)/human immunodeficiency virus (HIV). This large study aimed to assess demographics, STI/HIV burden, and sexual health care-seeking behavior of first-generation migrant and second-generation migrant male sex workers who have sex with men (MSW-MSM) versus Western-born MSW-MSM. METHODS: Coded STI clinic consultations (n = 6970) from 3116 individual MSW-MSM attending any Dutch STI clinic between 2016 and 2021 were included. First-generation migrant: born outside of northern/central/southern/western Europe/North America/Oceania. Second-generation migrant: ≥1parent born outside of northern/central/southern/western Europe/North America/Oceania. Multivariable logistic regression analysis assessed associations between MSW-MSM groups and STI in first consultation in the data. A Cox proportional hazard regression compared the incidence of a first repeat consultation between migration groups, stratified by STI in first consultation. All analyses were adjusted for age and urbanity of STI clinic region. RESULTS: First-generation migrant MSW-MSM (n = 1085) were mostly born in Latin America (50%), whereas second-generation migrant MSW-MSM (n = 368) mostly originated from North Africa (30.4%). The proportion of STI diagnoses differed (33.2%, 29.3%, 23.3%; P < 0.001) between the first-generation migrant, second-generation migrant, and Western-born MSW-MSM. First-generation migrant MSW-MSM versus Western-born had an adjusted odds ratio of 1.6 (95% confidence interval, 1.3-1.9) of STI diagnosis in the first consultation. First-generation migrant MSW-MSM versus Western-born had an adjusted hazard ratio of 1.5 (95% confidence interval, 1.3-1.8) of having a first repeat consultation at any time, when stratified for no STI in the first consultation. CONCLUSIONS: The STI/HIV burden is high among all 3 MSW-MSM groups. First-generation migrants have higher odds of STI, but retention in care seems similar. Results highlight the importance of low-threshold STI testing and care for (migrant) MSW-MSM.

Low Hepatitis C Virus Prevalence among Men Who Have Sex with Men Attending Public Health Services in The Netherlands.

The hepatitis C virus (HCV) prevalence is high among men who have sex with men (MSM) with HIV in the Netherlands. Large reductions in HCV incidence among MSM with HIV, however, have occurred since treatment with direct-acting antivirals. Over the years, a broader understanding of the HCV epidemic has shown that HCV infections are not solely restricted to MSM with HIV, but they also occur among HIV-negative MSM. Currently, HCV testing among HIV-negative MSM is only provided for PrEP users and is not part of routine sexually transmitted infection (STI) screening among HIV-negative MSM who are not using PrEP. In this study, we screened 1885 HIV-negative MSM who did not participate in a PrEP program, with over 1966 STI screening visits at four different public health clinic sites. Among the 1885 MSM, only one person had a new HCV infection, resulting in a 0.05% (95% confidence interval 0.0-0.3) incidence. Based on our findings, we can conclude that systematic HCV testing at STI clinics may not yield significant benefits for this particular population.

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

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

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

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

Determinants of adherence to daily PrEP measured as intracellular tenofovir diphosphate concentrations over 24 months of follow-up among men who have sex with men.

OBJECTIVES: Adherence is key to the effectiveness of oral pre-exposure prophylaxis (PrEP) to prevent HIV. Therefore, we aimed to explore factors associated with adherence to daily PrEP (dPrEP). METHODS: Men who have sex with men (MSM) using dPrEP (emtricitabine/tenofovir disoproxil) within the Amsterdam PrEP demonstration project at the Public Health Service of Amsterdam, provided dried blood spots (DBS) 12 and 24 months after PrEP initiation. From DBS, we determined intracellular tenofovir diphosphate (TFV-DP) concentrations to assess adherence; TFV-DP ≥700 fmol/punch was considered adequate. We assessed associations of sociodemographic, clinical and behavioural characteristics with TFV-DP concentrations using multivariable linear regression. RESULTS: Of 263 participants who attended 12-month or 24-month study visits while on dPrEP, 257 (97.7%) provided DBS at one or both visits (492 DBS in total). Median TFV-DP concentration was 1299 (IQR 1021-1627) fmol/punch (12 months: 1332 (1087-1687); 24 months: 1248 (929-1590]). Higher TFV-DP concentrations were associated with: older age (p=0.0008), condomless anal sex with a casual partner in 6 months preceding PrEP initiation (+166 fmol/punch; 95% CI 36.5 to 296) and using a mobile application providing visualised feedback on PrEP use and sexual behaviour (+146 fmol/punch; 95% CI 28.1 to 263). Lower TFV-DP concentrations were associated with longer duration of PrEP use (24 vs 12 months; -91.5 fmol/punch; 95% CI -155 to -28.1). Time-updated number of sex partners, diagnosed STIs and chemsex were not associated with TFV-DP concentrations. CONCLUSIONS: Overall, TFV-DP concentrations were high among MSM using dPrEP, indicating excellent adherence. Especially older participants, those who reported condomless anal sex with a casual partner prior to PrEP initiation and those who used an app with visualised feedback showed higher levels of adherence. As TFV-DP concentrations had decreased slightly at 2 years of PrEP use when compared with 1 year, we emphasise the importance of adherence counselling to those who continue using PrEP. TRIAL REGISTRATION NUMBER: NL5413.

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

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

Choosing event-driven and daily HIV pre-exposure prophylaxis - data from two European PrEP demonstration projects among men who have sex with men.

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

Transient Changes in Preexposure Prophylaxis Use and Daily Sexual Behavior After the Implementation of COVID-19 Restrictions Among Men Who Have Sex With Men.

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

Adherence to event-driven HIV PrEP among men who have sex with men in Amsterdam, the Netherlands: analysis based on online diary data, 3-monthly questionnaires and intracellular TFV-DP.

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

Improving adherence to daily preexposure prophylaxis among MSM in Amsterdam by providing feedback via a mobile application.

OBJECTIVE: Improving adherence to preexposure prophylaxis (PrEP) by providing automated feedback on self-reported PrEP use via a mobile application (app). DESIGN: Randomized clinical trial among MSM participating in the Amsterdam PrEP demonstration project (AMPrEP). METHODS: Eligible participants were randomized 1 : 1 to the control or intervention app. Both allowed daily reporting of sexual behaviour and medication intake; the intervention app also provided visual feedback. Dried blood spots collected at 12 and 24 months yielded intracellular tenofovir diphosphate concentrations (TFV-DP). We assessed proportions of participants with poor (TFV-DP <700 fmol/punch; primary outcome), good (TFV-DP ≥700 fmol/punch) and excellent (TFV-DP ≥1250 fmol/punch; secondary outcome) adherence at both time-points, and the association with the control or intervention app. RESULTS: We randomized 229 participants, 118 to the intervention and 111 to the control arm. The primary, per-protocol, analysis included 83 participants per arm. In total, 22/166 (13%) of participants adhered poorly, 144/166 (87%) good and 66/166 (40%) excellently. App feedback did not result in a lower proportion of participants with poor adherence [control: 9 of 83 (11%); intervention: 13 of 83 (16%); P = 0.36]. App feedback did result in a larger proportion of participants with excellent adherence [control: 26/83 (31%); intervention: 40/83 (48%); P = 0.026]. CONCLUSION: In this highly adherent population, app feedback did not improve the proportion of participants with poor adherence to PrEP.Clinical Trial Number Netherlands Trial Register: NL5413.

Understanding pre-exposure prophylaxis (PrEP) regimen use: Switching and discontinuing daily and event-driven PrEP among men who have sex with men.

BACKGROUND: Optimising HIV pre-exposure prophylaxis (PrEP) provision requires insight into preferences of PrEP regimens and PrEP discontinuation. We assessed regimen switching and discontinuation and their determinants among men who have sex with men (MSM) participating in the Amsterdam PrEP demonstration project. METHODS: Between 3-August-2015 and 31-May-2016, we enrolled MSM (n = 374) and TGP (n = 2) in a prospective, longitudinal study. Participants could choose between daily or event-driven PrEP regimens at enrolment and every 3 months. We assessed transition intensities (TI) and determinants of switching (i) between regimens, and (ii) from either regimen to discontinuing PrEP using a multi-state Markov model. PrEP discontinuation was defined as formally stopping study participation or having no study visit for ≥6 months. FINDINGS: Of 367 analysed participants, 73·3% chose daily and 26·7% event-driven PrEP at enrolment. Median follow-up was 3·1 years (IQR 2·9-3·2). 121 participants switched their PrEP regimen at least once (cumulative probability 34·2%, 95% CI 29·4-39·6), with 90 switches from event-driven to daily PrEP (TI 0·35/PY, 95% CI 0·29-0·44) and 113 switches from daily to event-driven PrEP (TI 0·16/PY, 95% CI 0·13-0·20). Switching from event-driven to daily PrEP was associated with younger age, not reporting sex with HIV-positive partners, chemsex, and sexual compulsivity. Switching from daily to event-driven PrEP were associated with younger age and lower sexual satisfaction. 67 participants discontinued PrEP (cumulative probability 17·7%, 95% CI 14·1-22·2), with no difference between regimens: event-driven (n = 23, TI 0·08/PY, 95% CI 0·05-0·13) and daily PrEP (n = 44, TI 0·06/PY, 95% CI 0·04-0·08). Discontinuing daily PrEP was associated with younger age, fewer casual partners, and higher number of condomless anal sex acts with casual partners. INTERPRETATION: Switching between PrEP regimens was common, while going from event-driven to daily PrEP use was associated with certain sexual-related determinants (i.e. chemsex, sexual compulsivity, no known HIV-positive partners). PrEP discontinuation rates were low and independent of regimens. PrEP care should consider the reasons for choice and switch of regimen and involve education on safely switching or discontinuing PrEP, especially among younger MSM. FUNDING: ZonMw, H-TEAM, RIVM, GGD research funds, Aidsfonds, Amsterdam Diner Foundation, Gilead Sciences, Gilead Sciences Europe Ltd, Janssen Pharmaceuticals, MAC AIDS Fund, ViiV Healthcare.

Human Immunodeficiency Virus-Negative Men Who Have Sex With Men Have an Altered T-Cell Phenotype and Bioenergy Metabolism.

BACKGROUND: We recently reported that the levels of activation, exhaustion, and terminal differentiation within the peripheral T-cell compartment were increased in men who have sex with men (MSM) compared with blood bank donors. During activation and differentiation, T cells undergo metabolic changes to maintain their energy demand. METHODS: The effect of cytomeglovirus (CMV) infection and risk behavior on the immune phenotype of peripheral T cells and the immune bioenergy metabolism profile in human immunodeficiency virus-negative MSM (with high or low sexual risk behavior) and blood bank donors was evaluated. RESULTS: Men who have sex with men exhibited increased levels of T-cell activation and terminal differentiation and an impairment of the bioenergy metabolism (mitochondrial respiration and glycolysis) compared with blood bank donors. Cytomeglovirus infection was associated with increased terminal differentiation of CD4+ (B = 3.41; 95% confidence interval [CI], 1.98-4.85; P < .0001) and CD8+ T cells (CD57+: B = 1.21, 95% CI = 0.41-2.02, P = .004; CD27-CD28-: B = 2.20, 95% CI = 1.21-3.18, P < .0001; and CD57+ of CD28-: B = 1.02, 95% CI = 0.38-1.66, P = .002) and increased glycolysis (B = 0.97; 95% CI, 0.27-1.67; P = .007). Risk behavior was associated with increase activation of CD4+ T cells (B = 0.22; 95% CI, 0.07-0.37; P = .005), increased terminal differentiation of CD4+ (B = 0.82; 95% CI, 0.44-1.20; P < .0001) and CD8+ T cells (B = 1.55; 95% CI, 0.58-2.51; P = .002), and decreased glycolysis (glycolysis: B = -0.40, 95% CI = -0.68 to 0.12, P = .006; and glycolytic capacity: B = -0.54, 95% CI = -0.91 to 0.16, P = .005). CONCLUSIONS: Men who have sex with men show an increased prevalence of bloodborne and sexually transmitted infection, indicating that immunological changes in the T-cell population and the bioenergy metabolism observed in MSM can most likely be attributed to chronic antigen exposure.

Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity.

Both the absence of cyclophilin D (CypD) and the presence of mitochondrial bound hexokinase II (mtHKII) protect the heart against ischemia/reperfusion (I/R) injury. It is unknown whether CypD determines the amount of mtHKII in the heart. We examined whether CypD affects mtHK in normoxic, ischemic and preconditioned isolated mouse hearts. Wild type (WT) and CypD-/- mouse hearts were perfused with glucose only and subjected to 25 min ischemia and reperfusion. At baseline, cytosolic and mtHK was similar between hearts. CypD ablation protected against I/R injury and increased ischemic preconditioning (IPC) effects, without affecting end-ischemic mtHK. When hearts were perfused with glucose, glutamine, pyruvate and lactate, the preparation was more stable and CypD ablation-resulted in more protection that was associated with increased mtHK activity, leaving little room for additional protection by IPC. In conclusion, in glucose only-perfused hearts, deletion of CypD is not associated with end-ischemic mitochondrial-HK binding. In contrast, in the physiologically more relevant multiple-substrate perfusion model, deletion of CypD is associated with an increased mtHK activity, possibly explaining the increased protection against I/R injury.