Co-Administration of Influenza and COVID-19 Vaccines: Policy Review and Vaccination Coverage Trends in the European Union, UK, US, and Canada between 2019 and 2023.

Recommending co-administration of influenza and COVID-19 vaccines has emerged as a strategy to enhance vaccination coverage. This study describes the policy on co-administration and uptake of influenza and COVID-19 vaccination in Europe, the United Kingdom, the United States, and Canada between 2019 and 2023. We collected co-administration policy data from governmental websites, national health organizations, and newspapers. Influenza vaccination coverage among persons ≥65 years and COVID-19 vaccination coverage rates among persons ≥60 years or the general population were collected using national databases, the ECDC database, or ourworldindata.org between 2019 and 2023. Descriptive analyses were used. We collected data from 30/32 (94%) countries on vaccination policy in seasons 2021-2022 and 2022-2023, with most countries (25/30 to 30/30) having policies recommending co-administration. For influenza vaccination coverage, we collected data from 29/32 (91%, 2019-2020), 28/32 (88%, 2020-2021), 27/32 (84%, 2021-2022), and 6/32 (19%, 2022-2023) countries. COVID-19 vaccination was collected from 32/32 (2020-2021), 31/32 (97%, 2021-2022), and 24/32 (75%, 2022-2023) countries. Influenza vaccination coverage increased from 2019-2020 to 2021-2022. COVID-19 vaccination coverage was higher among countries with higher influenza vaccination coverage. By 2022-2023, all countries included implemented a policy supporting co-administration. A positive correlation existed between higher influenza vaccination coverage and higher COVID-19 vaccination rates.

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.

The Impact of Pre-exposure Prophylaxis on Sexual Well-Being Among Men Who Have Sex with Men.

Pre-exposure prophylaxis (PrEP) is a promising strategy to reduce HIV incidence among men who have sex with men (MSM). How and when PrEP is used could in part be influenced by its impact on the sexual well-being of its users. Yet, the impact of PrEP on sexual well-being has received little attention in current literature and is not well-understood. We conducted 43 in-depth interviews (June 2017-June 2018) with HIV-negative MSM who started PrEP within the Amsterdam PrEP study. We used purposive sampling to select participants who (1) reported changes on well-being indicators; (2) switched between PrEP-dosing regimens; (3) neither changed regimens nor changed on well-being indicators. Transcribed interviews were qualitatively analyzed by means of an open-coding process. Results showed that PrEP minimized HIV-related fear, increased self-esteem, and reduced stigma and shame about having condomless anal sex. The psychological relief provided by PrEP also enabled relaxation which reduced pain during anal sex. PrEP use increased the diversity of partner choices and improved the perceived quality of sexual relationships and the ability to develop relationships. Along with this positive impact, almost half of interviewees reported concurrent negative experiences. In some cases, PrEP triggered more extreme sexual behaviors and/or problematic increases in preoccupation with sex and drug use. These were perceived as having a negative impact on sexual relationships, sexual well-being, PrEP adherence, and general health. In conclusion, our findings suggest that PrEP contributes to improvements in sexual well-being that go beyond protection from HIV. Counseling strategies should be devised to help PrEP users mitigate possible co-existing negative consequences of PrEP use.

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.

Latent classes of sexual risk and corresponding STI and HIV positivity among MSM attending centres for sexual health in the Netherlands.

OBJECTIVES: Continuing high STI positivity among men who have sex with men (MSM) attending centres for sexual health (CSH) indicates that high-risk behaviour is ongoing. The objective of this study was to gain a better insight into risk behaviours among MSM attending CSH and to explore STI and HIV positivity by subgroups. METHODS: We used national data routinely collected during CSH consultations for this study. From September to December 2017, questions on group sex, substance use and sex with HIV-positive partners were asked at each CSH consultation. We analysed latent classes of client-related factors and sexual risk behaviour among MSM attending CSH in this period. We examined STI positivity and prevalence ratios by latent classes. RESULTS: A total of six classes were identified in order of increasing risk: 'overall low-risk behaviour' (n=2974; 22.0%), 'Western origin and multiple sex partners' (MSP) (n=4182; 30.9%), 'Non-Western origin and MSP' (n=2496; 18.5%), 'living with HIV' (n=827; 6.1%), 'group sex and HIV-positive partners' (n=1798; 13.3%) and 'group sex and chemsex' (n=1239; 9.2%). The any STI positivity ranged from 14.0% in the overall low-risk behaviour class to 35.5% in the group sex and chemsex class. HIV positivity did not differ significantly between classes. The Western origin and MSP class was largest and accounted for the majority of STI and HIV infections. CONCLUSIONS: Although STI positivity increased with increased risky behaviours, considerable STI positivity was found in all six latent classes. Comparable HIV positivity between classes indicates risk reduction strategies among subgroups engaged in risky behaviours. The differences in risk behaviour and STI positivity require preventive strategies tailored to each subgroup.

Identification and characterization of latent classes based on drug use among men who have sex with men at risk of sexually transmitted infections in Amsterdam, the Netherlands.

BACKGROUND AND AIMS: Men who have sex with men (MSM) are at high risk for both drug use and sexually transmitted infections (STI). We aimed to (1) identify subgroups of drug use during sex among MSM in Amsterdam and after classifying participants and (2) compare sexual behaviour and STI across groups. DESIGN: Cross-sectional study. Latent class analysis was used to identify subgroups with similar drug use patterns, between which sexual behaviour and STI prevalence were compared. SETTING: Four different studies conducted at the STI out-patient clinic in Amsterdam, the Netherlands, between January 2014 and June 2016. PARTICIPANTS: A total of 1130 self-declared MSM, aged ≥ 18 years. MEASUREMENTS: Self-reported drug use, laboratory-confirmed STI, socio-demographics, sexual behaviour (including number of partners), condom use. FINDINGS: Median age was 40 years [interquartile range (IQR) = 32-47]. We identified five latent classes of users, which we labelled: 'no substance' (n = 162), 'alcohol' (n = 159), 'nitrites and erectile dysfunction drugs (EDD)' (n = 286), 'polydrug' (n = 257) and 'chems' (n = 266). Median number of sex partners significantly differed across classes (P < 0.001), ranging from two (IQR = 1-6) in the 'no substance' class to 20 (IQR = 10-45) in the 'chems' class. The proportion of MSM reporting condomless anal sex also differed across classes (P < 0.001), ranging from 45.6% in the 'no substance' class to 86.5% in the 'chems' class. Compared with the 'no substance' class, the odds of STI were 3.9-fold [95% confidence interval (CI) = 1.1-14.4] higher in the 'alcohol' class, 8.9-fold (95% CI = 2.7-29.2) higher in the 'nitrites and EDD' class, 12.8-fold (95% CI = 3.9-41.9) higher in the 'polydrug' class and 15.0-fold (95% CI = 4.6-48.8) higher in the 'chems' class. CONCLUSION: There are five distinct classes of drug use in a sexual context among men who have sex with men in Amsterdam, the Netherlands. Classes with higher levels of drug use appear to coincide with higher levels of sexual risk behaviour and sexually transmitted infections.

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

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

A Mobile Application to Collect Daily Data on Preexposure Prophylaxis Adherence and Sexual Behavior Among Men Who Have Sex With Men: Use Over Time and Comparability With Conventional Data Collection.

BACKGROUND: We studied the use of a mobile application (app) to measure human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) adherence and sexual behavior, assessed determinants of app use, and we compared data in app and questionnaires. METHODS: Men who have sex with men participating in the Amsterdam PrEP project (AMPrEP) on daily or event-driven PrEP at the Public Health Service of Amsterdam completed the data on sexual risk behavior and PrEP adherence through a standard questionnaire every 3 months and on a daily basis using the project's app. Regression analyses were used to assess factors associated with app use. Among those who reported 90% or greater of data in the app, the number of PrEP pills taken and number of unknown casual sex partners were compared between the app and the questionnaires by Wilcoxon signed-rank test. RESULTS: Of all participants (n = 374), 94% (352 of 374) reported data in the app at least once; 72% (261 of 362) reported data ≥90% of the days in the sixth month and 62% (222 of 359) in the 12th month following PrEP initiation.Factors associated with reporting data in the app were using daily PrEP and recent initiation of PrEP. The reported numbers of pills taken and unknown sexual partners were comparable between app and questionnaires. CONCLUSIONS: The AMPrEP app was used frequently, especially by those using a daily PrEP regimen. Data collected by app regarding adherence and sexual risk behavior were consistent with questionnaire data among those who used the app consistently. An app is a promising tool to measure PrEP adherence and sexual risk behavior.

Acquisition of wild-type HIV-1 infection in a patient on pre-exposure prophylaxis with high intracellular concentrations of tenofovir diphosphate: a case report.

BACKGROUND: Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly effective against acquisition of HIV infection, and only two cases of infection with a multidrug-resistant virus have been reported under adequate long-term adherence, as evidenced by tenofovir diphosphate concentrations in dried blood spots. We report a case of wild-type HIV-1 infection despite consistent use of emtricitabine and tenofovir disoproxil fumarate. METHODS: The patient participated in the Amsterdam PrEP project, a demonstration project of daily and event-driven PrEP. We did extensive testing for HIV, including plasma HIV RNA and nested PCR on bulk peripheral blood mononuclear cells (PBMCs) and sigmoid biopsies after seroconversion. FINDINGS: A 50-year-old man who has sex with men and had been on daily emtricitabine and tenofovir disoproxil fumarate for 8 months presented with fever, urinary tract infection caused by Escherichia coli, anal lymphogranuloma venereum infection, and a positive fourth-generation HIV test. We found an atypical seroconversion pattern, with initially only gp160 antibodies detected in the western blot. HIV RNA could not be detected in plasma, and nested PCR for HIV RNA and DNA on bulk PBMCs and sigmoid biopsies were negative. PrEP was discontinued; 3 weeks later HIV RNA was detected in plasma. No drug-resistant mutations were detected. Tenofovir diphosphate concentrations in dried blood spots were stable and high. INTERPRETATION: To our knowledge, this is the first detailed case report suggesting wild-type HIV-1 infection despite good adherence, evidenced by repeatedly high concentrations of tenofovir diphosphate in dried blood spots. PrEP providers need to be aware that infection can occur despite good adherence. Regular HIV testing and awareness of atypical patterns of seroconversion is highly recommended. FUNDING: ZonMw, National Institute for Public Health and the Environment, Internal GGD research funds, Aidsfonds, Stichting AmsterdamDiner Foundation, Gilead Sciences, Janssen Pharmaceutica, M A C AIDS Fund, and ViiV Healthcare.

Design of a syndemic based intervention to facilitate care for men who have sex with men with high risk behaviour: the syn.bas.in randomized controlled trial.

BACKGROUND: Men who have sex with men (MSM) constitute a risk group for sexual transmitted infections (STIs), including HIV. Despite counselling interventions, risk behaviour remains high. Syndemic theory holds that psychosocial problems often co-occur, interact and mutually reinforce each other, thereby increasing high risk behaviours and co-occurring diseases. Therefore, if co-occurring psychosocial problems were assessed and treated simultaneously, this might decrease high risk behaviour and disease. METHOD: An open label randomized controlled trial will be conducted among 150 MSM with high risk behaviour recruited from the STI clinic of Amsterdam. Inclusion criteria are: HIV negative MSM with two STI and/or PEP treatment in the last 24 months, or HIV positive MSM with one STI in the last 24 months. All participants get questionnaires on the following syndemic domains: ADHD, depression, anxiety disorder, alexithymia and sex- and drug addiction. Participants in the control group receive standard care: STI screenings every three months and motivational interviewing based counselling. Participants in the experimental group receive standard care plus feedback based on the results of the questionnaires. All participants can be referred to co-located mental health or addiction services. The primary outcome is help seeking behaviour for mental health problems and/or drug use problems. The secondary outcomes are STI incidence and changes in sexual risk behaviour (i.e. condom use, number of anal sex partners, drug use during sex). DISCUSSION: This study will provide information on syndemic domains among MSM who show high risk behaviour and on the effect of screening and referral on help seeking behaviour and health (behaviour) outcomes. TRIAL REGISTRATION: Trial Registration at clinicaltrail.gov, identifier NCT02859935 .

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

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