2022

Publication

“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“. De la Court, F., Boyd, A., Coyer, L., Van den Elshout, M., De Vries, H.J.C., Matser, A., Hoornenborg, E., Prins, M. on behalf of the HIV Transmission Elimination AMsterdam (H-TEAM) Consortium. HIV Med. 13, doi: 10.111/hiv.13374.

Abstract

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.

Keywords
COVID-19; men who have sex with men; pre-exposure prophylaxis; sexual healthcare use; sexually transmitted infections.

Publication

“Estimating the potential to prevent locally acquired HIV infections in a UNAIDS Fast-Track City, Amsterdam“. Blenkinsop, A., Monod, M., Van Sighem, A., Pantazis, N., Bezemer, D., Op de Coul, E., Van de Laar, T., Fraser, C., Prins, M., Reiss, P., De Bree, G.J., Ratmann, O. eLife 11: e76487, doi: 10.7554/eLife.76487.

Abstract

Background
More than 300 cities including the city of Amsterdam in the Netherlands have joined the UNAIDS Fast-Track Cities initiative, committing to accelerate their HIV response and end the AIDS epidemic in cities by 2030. To support this commitment, we aimed to estimate the number and proportion of Amsterdam HIV infections that originated within the city, from Amsterdam residents. We also aimed to estimate the proportion of recent HIV infections during the 5-year period 2014-2018 in Amsterdam that remained undiagnosed.

Methods
We located diagnosed HIV infections in Amsterdam using postcode data (PC4) at time of registration in the ATHENA observational HIV cohort, and used HIV sequence data to reconstruct phylogeographically distinct, partially observed Amsterdam transmission chains. Individual-level infection times were estimated from biomarker data, and used to date the phylogenetically observed transmission chains as well as to estimate undiagnosed proportions among recent infections. A Bayesian Negative Binomial branching process model was used to estimate the number, size and growth of the unobserved Amsterdam transmission chains from the partially observed phylogenetic data.

Results
Between January 1 2014 and May 1 2019, there were 846 HIV diagnoses in Amsterdam residents, of whom 516 (61%) were estimated to have been infected in 2014-2018. The rate of new Amsterdam diagnoses since 2014 (104 per 100,000) remained higher than the national rates excluding Amsterdam (24 per 100,000), and in this sense Amsterdam remained a HIV hotspot in the Netherlands. An estimated 14% [12-16%] of infections in Amsterdan MSM in 2014-2018 remained undiagnosed by May 1 2019, and 41% [35-48%] in Amsterdam heterosexuals, with variation by region of birth. An estimated 68% [61-74%] of Amsterdam MSM infections in 2014-2018 had an Amsterdam resident as source, and 57% [41-71%] in Amsterdam heterosexuals, with heterogeneity by region of birth. Of the locally acquired infections, an estimated 43% [37-49%] were in foreign-born MSM, 41% [35-47%] in Dutch-born MSM, 10% [6-18%] in foreign-born heterosexuals, and 5% [2-9%] in Dutch-born heterosexuals. We estimate the majority of Amsterdam MSM infections in 2014-2018 originated in transmission chains that pre-existed by 2014.

Conclusions
This combined phylogenetic, epidemiologic, and modelling analysis in the UNAIDS Fast-Track City Amsterdam indicates that there remains considerable potential to prevent HIV infections among Amsterdam residents through city-level interventions. The burden of locally acquired infection remains concentrated in MSM, and both Dutch-born and foreign-born MSM would likely benefit most from intensified city-level interventions.

Funding
This study received funding as part of the H-TEAM initiative from Aidsfonds (project number P29701). The H-TEAM initiative is being supported by Aidsfonds (grant number: 2013169, P29701, P60803), Stichting Amsterdam Dinner Foundation, Bristol-Myers Squibb International Corp. (study number: AI424-541), Gilead Sciences Europe Ltd (grant number: PA-HIV-PREP-16-0024), Gilead Sciences (protocol numbers: CO-NL-276-4222, CO-US-276-1712, CO-NL-985-6195), and M.A.C AIDS Fund.

Publication

“Can we screen less frequently for STI among PrEP users? Assessing the effect of biannual STI screening on timing of diagnosis and transmission risk in the AMPrEP Study”. Jongen, V.W., Zimmerman, H.M.L., Goedhart, M., Bogaards J.A., Davidovich, U., Coyer L., de Vries H.J.C., Prins M., Hoornenborg E., Schim van der Loeff M.F. on behalf of the Amsterdam PrEP Project Team in the HIV Transmission Elimination Amsterdam (H-TEAM) initiative. Sex Transm Infect 2022 (online publication ahead of print), doi: 10.113/sextrans-2022-055439.

Abstract

Background
In many countries, HIV pre-exposure prophylaxis (PrEP) users are screened quarterly for STIs. We assessed the consequences of less frequent STI testing. We also assessed determinants of asymptomatic STI and potential for onward transmission.

Methods
Using data from the AMPrEP study, we assessed the proportion of syphilis, and genital, anal, and pharyngeal chlamydia and gonorrhoea diagnoses which would have been delayed with biannual versus quarterly screening. We assessed the potential for onward transmission by examining reported condomless anal sex (CAS) in periods after to-be-omitted visits when screening biannually. We assessed determinants of incident asymptomatic STIs using Poisson regression and calculated individual risk scores on the basis of the coefficients from this model.

Results
We included 366 participants. Median follow-up was 47 months (IQR 43-50). 1,183STIs were diagnosed, of which 932(79%) asymptomatic. With biannual screening, 483 asymptomatic STIs (52%) diagnoses would have been delayed at 364 study visits. Of these visits, 129 (35%), 240 (66%) and 265 (73%) were followed by periods of CAS with steady, known casual or unknown casual partners, respectively. Older participants had a lower risk of asymptomatic STI (incidence rate ratio (IRR) 0.86/10-year increase, 95% CI 0.80 to 0.92), while CAS with known (IRR 1.36, 95% CI 1.10 to 1.68) and unknown (IRR 1.86, 95% CI 1.48 to 2.34) casual partners and chemsex (IRR 1.51, 95% CI 1.28 to 1.78) increased the risk. The individual risk scores had limited predictive value (sensitivity=0.70 (95% CI 0.66 to 0.74), specificity=0.50 (95% CI 0.48 to 0.51)).

Conclusion
Reducing the STI screening frequency to biannually among PrEP users will likely result in delayed diagnoses, potentially driving onward transmission. Although determinants for asymptomatic STIs were identified, predictive power was low.

Keywords
Chlamydia Infections; NEISSERIA GONORRHOEAE; PREP; Pre-Exposure Prophylaxis; SYPHILIS.

Publication

“Perceptions of HIV cure and willingness to participate in HIV cure-related trials among people enrolled in the Netherlands cohort study on acute HIV infection”. Van Paassen, P., Dijkstra, M., Peay, H.L., Rokx, C., Verbon, A., Reiss, P., Prins, J.M., Henderson, G.E., Rennie, S., Nieuwkerk, P.T., de Bree, G.J. Journal of Virus Eradication 2022, doi: https://doi.org/10.1016/j.jve.2022.100072.

Abstract

Background
People who initiate antiretroviral therapy (ART) during acute HIV infection are potential candidates for HIV cure-related clinical trials, as early ART reduces the size of the HIV reservoir. These trials, which may include ART interruption (ATI), might involve potential risks. We explored knowledge and perception of HIV cure and willingness to participate in cure-related trials among participants of the Netherlands Cohort Study on Acute HIV infection (NOVA study), who started antiretroviral therapy immediately after diagnosis of acute HIV infection.

Methods
We conducted 20 in-depth qualitative interviews with NOVA study participants between October-December 2018. Data were analyzed thematically, using inductive and iterative coding techniques.

Findings
Most participants had limited knowledge of HIV cure and understood HIV cure as complete eradication of HIV from their bodies. HIV cure was considered important to most participants, mostly due to the stigma surrounding HIV. More than half would consider undergoing brief ATI during trial participation, but only one person considered extended ATI. Viral rebound and increased infectiousness during ATI were perceived as large concerns. Participants remained hopeful of being cured during trial participation, even though they were informed that no personal medical benefit was to be expected.

Interpretation
Our results highlight the need for thorough informed consent procedures with assessment of comprehension and exploration of personal motives prior to enrollment in cure-related trials. Researchers might need to moderate their expectations about how many participants will enroll in a trial with extended ATI.

2021

Publication

“Offering a choice of daily and event-driven preexposure prophylaxis for men who have sex with men in the Netherlands: a cost-effectiveness analysis”. Van Hoek, A.J., Reitsema, M., Xiridou, M., Van Sighem, A., Van Benthem, B., Wallinga, J., van Duijnhoven, Y., Van der Loeff, M.F., Prins, M., Hoornenborg, E. the Amsterdam PrEP Project team in the HIV Transmission Elimination Amsterdam (H-TEAM) Initiative. AIDS 35(10): 1677-1682, doi: 10.1097/QAD.0000000000002913.

Abstract
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.
Publication

“Improving adherence to daily preexposure prophylaxis among MSM in Amsterdam by providing feedback via a mobile application”. Van den Elshout, M.A.M., Hoornenborg, E., Achterbergh, R.C.A., Coyer, L., Anderson, P.L., Davidovich, U., de Vries, H.J.C., Prins, M., Van der Loeff, M.F. the Amsterdam PrEP Project team in the HIV Transmission Elimination Amsterdam (H-TEAM) Initiative. AIDS 35(11): 1823-1834, doi: 10.1097/QAD.0000000000002949.

Abstract
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.
Publication

“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”. Jongen, V.W., Hoornenborg, E., Van den Elshout, M.A.M., Boyd, A., Zimmermann, H.M.L., Coyer, L., Davidovich, U., Anderson, P.L., de Vries, H.J.C., Prins, M., Schim van der Loeff, M.F. the Amsterdam PrEP Project team in the HIV Transmission Elimination Amsterdam (H-TEAM) Initiative. Journal of th eInternational Aids Society 24(5): e25708, doi: 10.1002/jia2.25708.

Abstract

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.
Publication

“Cohort profile: the Netherlands Cohort Study on Acute HIV infection (NOVA), a prospective cohort study of people with acute or early HIV infection who immediately initiate HIV treatment”. Dijkstra, M., Prins, H., Prins, J.M., Reiss, P., Boucher, C., Verbon, A., Rokx, C., de Bree, G.J. BMJ Open 2021;11:e048582, doi: 10.1136/bmjopen-2020-048582.

Abstract

Purpose
Initiation of combination antiretroviral therapy (cART) during acute or early HIV-infection (AEHI) limits the size of the viral reservoir and preserves immune function. This renders individuals who started cART during AEHI promising participants in HIV-cure trials. Therefore, we established a multicentre prospective cohort study in the Netherlands that enrols people with AEHI. In anticipation of future cure trials, we will longitudinally investigate the properties of the viral reservoir size and HIV-specific immune responses  among cohort participants.

Participants
Participants immediately initiate intensified cART: dolutegravir, emtricitabine/tenofovir and darunavir/ritonavir (DRV/r). After  weeks, once baseline resistance data are available, DRV/r is discontinued. Three study groups are assembled based on the  preparedness of individuals to participate in the extensiveness of sampling. Participants accepting immediate treatment and follow-up but declining additional sampling are included in study group 1 (‘standard’) and routine diagnostic procedures are performed. Participants willing to undergo blood, leukapheresis and semen sampling are included in study group 2 (‘less invasive’). In study group 3 (‘extended’), additional tissue (gut-associated lymphoid tissue, peripheral lymph node) and cerebrospinal fluid sampling are performed.

Findings to date
Between 2015 and 2020, 140 individuals with AEHI have been enrolled at nine study sites. At enrolment, median age was 36 (IQR  8–47) years, and 134 (95.7%) participants were men. Distribution of Fiebig stages was as follows: Fiebig I, 3 (2.1%); II, 20 (14.3%); III, 7  (5.0%); IV, 49 (35.0%); V, 39 (27.9%); VI, 22 (15.7%). Median plasma HIV RNA was 5.9 (IQR 4.7–6.7) log10 copies/mL and CD4  count 510 (IQR 370–700) cells/mm3. Median time from cART initiation to viral suppression was 8.0 (IQR 4.0–16.0) weeks.

Future plans
The Netherlands Cohort Study on Acute HIV infection remains open for participant enrolment and for additional sites to join the  network. This cohort provides a unique nationwide platform for conducting future in-depth virological, immunological, host genetic and interventional studies investigating HIV-cure strategies.

Publication

“Prevention challenges with current perceptions of HIV burden among HIV-negative and never-tested men who have sex with men in the Netherlands: a mixed-methods study”. Zimmermann, H.M., van Bilsen, W.P., Boyd, A., Prins, M., van Harreveld, F., Davidovich, U. for the HIV Transmission Elimination Team Amsterdam. J Int AIDS Soc. 24(8):e25715, doi: 10.1002/jia2.25715.

Abstract

Introduction
As biomedical advances improved HIV treatment, the perceptions of severity and anticipated consequences of HIV could have changed accordingly. This study investigates the current perceptions of severity and anticipated consequences of HIV infection and its association with sexual risk behaviour among HIV-negative and never-tested men who have sex with men (MSM) living in the Netherlands.

Methods
In-depth interviews with recently diagnosed HIV-positive MSM were used to develop a questionnaire measuring the perceived severity and anticipated consequences of HIV infection. The questionnaire was distributed online between April and July 2019. A structural equation model was constructed to explore the anticipated consequences contributing to the perceived HIV severity and to assess the association between the perceived severity and sexual risk behaviour.

Results
In total, 1,072 HIV-negative and never-tested MSM completed the questionnaire, of whom 28% reported recent sexual risk behaviour. Almost one-quarter of participants (23%) had a low perceived HIV severity, which was associated with more prevalent sexual risk taking (β = -0.07, 95% CI = -0.12/-0.01). In this model, the perceived severity of HIV was more strongly associated with anticipated psychological consequences of HIV (β = 0.34, 95% CI = 0.24 to 0.44) and to a lesser extent with anticipated negative consequences of HIV on sex/relationships (β = 0.28, 95% CI = 0.19 to 0.38) and disclosure-related consequences (β = 0.16, 95% CI = 0.07 to 0.26). Health-related consequences of HIV were not significantly associated with the severity perceptions (β = 0.06, 95% CI = -0.03 to 0.14).

Conclusions
Anticipated negative social and psychological consequences of HIV mostly contribute to high HIV-severity perceptions in MSM. A smaller subgroup of MSM does not perceive HIV as a serious disease, which is associated with increased sexual risk taking. Efforts to normalize living with HIV are essential but might present a challenge for HIV prevention as it could, for a minority of MSM, decrease the motivation to prevent HIV infection.

Keywords: HIV; burden; men who have sex with men; prevention and control; sexual risk behaviour.

Introduction
As biomedical advances improved HIV treatment, the perceptions of severity and anticipated consequences of HIV could have changed accordingly. This study investigates the current perceptions of severity and anticipated consequences of HIV infection and its association with sexual risk behaviour among HIV-negative and never-tested men who have sex with men (MSM) living in the Netherlands.

Methods
In-depth interviews with recently diagnosed HIV-positive MSM were used to develop a questionnaire measuring the perceived severity and anticipated consequences of HIV infection. The questionnaire was distributed online between April and July 2019. A structural equation model was constructed to explore the anticipated consequences contributing to the perceived HIV severity and to assess the association between the perceived severity and sexual risk behaviour.

Results
In total, 1,072 HIV-negative and never-tested MSM completed the questionnaire, of whom 28% reported recent sexual risk behaviour. Almost one-quarter of participants (23%) had a low perceived HIV severity, which was associated with more prevalent sexual risk taking (β = -0.07, 95% CI = -0.12/-0.01). In this model, the perceived severity of HIV was more strongly associated with anticipated psychological consequences of HIV (β = 0.34, 95% CI = 0.24 to 0.44) and to a lesser extent with anticipated negative consequences of HIV on sex/relationships (β = 0.28, 95% CI = 0.19 to 0.38) and disclosure-related consequences (β = 0.16, 95% CI = 0.07 to 0.26). Health-related consequences of HIV were not significantly associated with the severity perceptions (β = 0.06, 95% CI = -0.03 to 0.14).

Conclusions
Anticipated negative social and psychological consequences of HIV mostly contribute to high HIV-severity perceptions in MSM. A smaller subgroup of MSM does not perceive HIV as a serious disease, which is associated with increased sexual risk taking. Efforts to normalize living with HIV are essential but might present a challenge for HIV prevention as it could, for a minority of MSM, decrease the motivation to prevent HIV infection.

Keywords: HIV; burden; men who have sex with men; prevention and control; sexual risk behaviour.

Publication

“Factors Associated with Never Testing for HIV: Directions for Targeted Testing Interventions Among Men Who Have Sex with Men”. Van Bilsen, W.P.H., Zimmermann, H.M.L., Boyd, A., van Harreveld, F., Davidovich, U. AIDS Patient Care STDS 35(6): 204-210, doi: 10.1089/apc.2021.0024.

Abstract

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.

Keywords: Amsterdam; HIV; men who have sex with men; sexual risk behavior; the Netherlands.

Publication

The Burden of Living With HIV is Mostly Overestimated by HIV-Negative and Never-Tested Men Who Have Sex With Men. “. Zimmermann, H.M.L., van Bilsen, W.P.H., Boyd, A., Matser, A., van Harreveld, F,, Davidovich, U. for the HIV Transmission Elimination Amsterdam Initiative. AIDS Behav. 2021, doi: 10.1007/s10461-021-03281-1.

Abstract

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.

Keywords: Burden; HIV; Male; Men who have sex with men; Quality of life; Social stigma.

Publication

Who is providing HIV diagnostic testing? Comparing HIV testing by general practitioners and sexual health centres in five regions in the Netherlands, 2011-2018“. Bogers, S.J., Twisk, D.E., Beckers, L.M., Götz, H.M., Meima, B., Kroone, M., Hoornenborg, E., Ott, A., Luning-Koster, M.N., Dukers-Muijrers, N.H.T.M., Hoebe, C.J.P.A., Kampman, C.J.G., Bosma, F., Schim van der Loeff, Geerlings, S.E., van Bergen, J.E.A.M. Sex Transm Infect. 2021: 055109, doi: 10.1136/sextrans-2021-055109.

Abstract

Objectives: General practitioners (GPs) and sexual health centres (SHCs) are the main providers of HIV testing and diagnose two-thirds of HIV infections in the Netherlands. We compared regional HIV testing and positivity by GPs versus SHCs to gain insight into strategies to improve HIV testing, to enable timely detection of HIV infections.

Methods: Laboratory data (2011-2018) on HIV testing by GPs and SHCs in five Dutch regions with varying levels of urbanisation were evaluated. Regional HIV testing rates per 10 000 residents ≥15 years (mean over period and annual) were compared between providers using negative binomial generalised additive models and additionally stratified by sex and age (15-29 years, 30-44 years, 45-59 years, ≥60 years). χ2 tests were used to compare positivity percentage between the two groups of providers.

Results: In the study period, 505 167 HIV tests (GP 36%, SHC 64%) were performed. The highest HIV testing rates were observed in highly urbanised regions, with large regional variations. The HIV testing rates ranged from 28 to 178 per 10 000 residents by GPs and from 30 to 378 per 10 000 by SHCs. Testing rates by GPs were lower than by SHCs in three regions and comparable in two. In all regions, men were tested less by GPs than by SHCs; for women, this varied by region. Among those aged 15-29 years old, GPs’ testing rates were lower than SHCs’, while this was reversed in older age categories in four out of five regions. The overall mean HIV positivity was 0.4%. In contrast to other regions, positivity in Amsterdam was significantly higher among individuals tested by GPs than by SHCs.

Conclusions: This retrospective observational study shows that besides SHCs, who perform opt-out testing for key groups, GPs play a prominent role in HIV testing, especially in non-key populations, such as women and older individuals. Large regional variation exists, requiring region-specific interventions to improve GPs’ HIV testing practices.

Keywords: HIV; epidemiology; general practice; primary health care; sexual health.

Publication

Promoting HIV indicator condition-guided testing in hospital settings (PROTEST 2.0): study protocol for a multicentre interventional study“. Bogers, S.J., Schim van der Loeff, Davidovich, U., Boyd, A., van der Valk, M., Brinkman, K., de Bree, G.J., Reiss, P., van Bergen, J.E.A.M., Geerlings, S.E., for the HIV Transmission Elimination Amsterdam (H-TEAM) initiative. BMC Infect Dis 21(1): 519, doi: 10.1186/s12879-021-06183-8.

Abstract

Background: Late presentation remains a key barrier towards controlling the HIV epidemic. Indicator conditions (ICs) are those that are AIDS-defining, associated with a prevalence of undiagnosed HIV > 0.1%, or whose clinical management would be impeded if an HIV infection were undiagnosed. IC-guided HIV testing is an effective strategy in identifying undiagnosed HIV, but opportunities for earlier HIV diagnosis through IC-guided testing are being missed. We present a protocol for an interventional study to improve awareness of IC-guided testing and increase HIV testing in patients presenting with ICs in a hospital setting.

Methods: We designed a multicentre interventional study to be implemented at five hospitals in the region of Amsterdam, the Netherlands. Seven ICs were selected for which HIV test ratios (proportion of patients with an IC tested for HIV) will be measured: tuberculosis, cervical/vulvar cancer or high-grade cervical/vulvar dysplasia, malignant lymphoma, hepatitis B and C, and peripheral neuropathy. Prior to the intervention, a baseline assessment of HIV test ratios across ICs will be performed in eligible patients (IC diagnosed January 2015 through May 2020, ≥18 years, not known HIV positive) and an assessment of barriers and facilitators for HIV testing amongst relevant specialties will be conducted using qualitative (interviews) and quantitative methods (questionnaires). The intervention phase will consist of an educational intervention, including presentation of baseline results as competitive graphical audit and feedback combined with discussion on implementation and opportunities for improvement. The effect of the intervention will be assessed by comparing HIV test ratios of the pre-intervention and post-intervention periods. The primary endpoint is the HIV test ratio within ±3 months of IC diagnosis. Secondary endpoints are the HIV test ratio within ±6 months of diagnosis, ratio ever tested for HIV, HIV positivity percentage, proportion of late presenters and proportion with known HIV status prior to initiating treatment for their IC.

Discussion: This protocol presents a strategy aimed at increasing awareness of the benefits of IC-guided testing and increasing HIV testing in patients presenting with ICs in hospital settings to identify undiagnosed HIV in Amsterdam, the Netherlands.

Trial registration: Dutch trial registry: NL7521. Registered 14 February 2019.

Publication

Current evidence on the adoption of indicator condition guided testing for HIV in western countries: A systematic review and meta-analysis“. Bogers, S.J., Hulstein, S.H., Schim van der Loeff, de Bree, G.J., Reiss, P., van Bergen, J.E.A.M., Geerlings, S.E. for the HIV Transmission Elimination Amsterdam (H-TEAM) initiative. EClinicalMedicine 35: 100877, doi: 10.1016/j.eclinm.2021.100877.

Abstract

Background: Indicator condition (IC) guided testing for HIV is an effective way to identify undiagnosed people living with HIV, but studies suggest its implementation is lacking. This systematic review provides an overview of the adoption of IC-guided testing in Western countries.

Methods: Seven ICs were selected: tuberculosis (TB), malignant lymphoma, hepatitis B, hepatitis C, cervical/vulvar carcinoma/intraepithelial neoplasia grade 2+ (CC/CIN2+, VC/VIN2+), and peripheral neuropathy (PN). Embase and Ovid MEDLINE were searched up to November 20th, 2020. Publications of all types, using data from ≥2009, reporting on HIV test ratios in patients ≥18 years in all settings in Western countries were eligible. HIV test ratios and positivity were reported per IC. A random effects-model for proportions was used to calculate estimated proportions (ES) with 95% CIs. This study was registered at PROSPERO, registration number CRD42020160243.

Findings: Fifty-seven references, including 23 full-text articles and 34 other publications were included. Most (28/57) reported on HIV testing in TB. No reports on HIV testing in VC/VIN2+ or PN patients were eligible for inclusion. Large variation in HIV test ratios was observed between and within ICs, resulting from different testing approaches. Highest HIV test ratios (pooled ratio: 0·72, 95%CI 0·63–0·80) and positivity (0·05, 95% CI 0·03–0·06) were observed among TB patients, and lowest among CC/CIN2+ patients (pooled ES test ratio: 0·12, 95%CI 0·01–0·31, positivity: 0·00, 95%CI 0·00–0·00).

Interpretation: IC-guided HIV testing is insufficiently implemented in Western countries. The large variation in test ratios provides insight into priority areas for implementing routine IC-guided HIV testing in the future.

Funding: HIV Transmission Elimination in Amsterdam (H-TEAM) consortium and Aidsfonds (grant number P-42,702).

Publication

Rationale, design and initial results of an educational intervention to improve provider-initiated HIV testing in primary care“. Bogers, S.J., Schim van der Loeff, M.F., van Dijk, N., Groen, K., Groot Bruinderink, M.L., de Bree, G.J., Reiss, P., Geerlings, S.E., van Bergen, J.E.A.M. Fam Pract. 38(4): 441-447, doi: 10.1093/fampra/cmaa139.

Abstract

Objectives: In the Netherlands, general practitioners (GPs) perform two-thirds of sexually transmitted infection (STI) consultations and diagnose one-third of HIV infections. GPs are, therefore, a key group to target to improve provider-initiated HIV testing. We describe the design and implementation of an educational intervention to improve HIV testing by Amsterdam GPs and explore trends in GPs’ testing behaviour.

Methods: Interactive sessions on HIV and STI using graphical audit and feedback started in 2015. Participating GPs developed improvement plans that were evaluated in follow-up sessions. Laboratory data on STI testing by Amsterdam GPs from 2011 to 2017 were collected for graphical audit and feedback and effect evaluation. The primary outcome was the HIV testing rate: number of HIV tests per 10 000 person-years (PY). Secondary endpoints were chlamydia and gonorrhoea testing rates and HIV positivity ratios.

Results: Since 2015, 41% of GPs participated. HIV testing rate declined from 2011 to 2014 (from 175 to 116 per 10 000 PY), more in women than men (176 to 101 versus 173 to 132), and stabilized from 2015 to 2017. The HIV positivity ratio declined from 0.8% in 2011 to 0.5% in 2017. From 2011 to 2017, chlamydia and gonorrhoea testing rates declined in women (from 618 to 477 per 10 000 PY) but remained stable in men (from 270 to 278).

Conclusions: The stabilization of the downward trend in HIV testing coincided with this educational intervention. Follow-up data are needed to formally assess the intervention’s impact on GP testing behaviour whilst considering contextual factors and secular trends.

Keywords: HIV; continuing medical education; general practice; primary care; quality improvement; sexually transmitted disease.

Publication

Understanding Reasons for HIV Late Diagnosis: A Qualitative Study Among HIV-Positive Individuals in Amsterdam, The Netherlands“. Bedert, M., Davidovich, U., de Bree, G., van Bilsen, W., van Sighem, A., Zuilhof, W., Brinkman, K., van der Valk, M., de Wit, J. for the HIV Transmission Elimination Amsterdam (H-TEAM) initiative. AIDS and Behavior (2021), doi: 10.1007/s10461-021-03239-3. 

Abstract
Since the introduction of effective anti-retroviral therapy, early diagnosis and treatment of HIV have become increasingly important from individual and public health perspectives. People who are diagnosed with a CD4 count below 350 cells/µL blood are today considered to be “late” diagnoses. In an effort to understand the reasons for late diagnosis, we conducted in-depth interviews (n = 14) in Amsterdam, the Netherlands. Two main factors were identified: psychosocial factors and health-system factors. Psychosocial factors relate to people’s personal relationship with health professionals, low risk perception, fear related to the outcome of testing, and trauma from observed past experiences of living with HIV. Health-system factors relate to institutional barriers and missed opportunities during client-provider interactions. We conclude that in order to mitigate late diagnosis, the social and institutional context within which HIV testing is conducted should be addressed.

2020

Publication

Decision-making regarding condom use among daily and event-driven users of preexposure prophylaxis in the Netherlands“. Zimmerman, H.M.L., Jongen, V.W., Boyd, A., Hoornenborg, E., Prins, M., De Vries, H.J.C., Schim van der Loeff, M.F.S., Davidovich, U. Amsterdam PrEP Project Team in the HIV Transmission Elimination Amsterdam Inititative (H-TEAM). AIDS 34(15) 2295-2304, doi: 10.1097/QAD.0000000000002714.

Abstract

Objective
To explore the frequency of and reasons for using condoms among men who have sex with men (MSM) on preexposure prophylaxis (PrEP).

Design
We analyzed quantitative app-based diary data on daily sexual practices (August 2015-February 2019) and qualitative in-depth interviews among MSM using daily PrEP and event-driven PrEP (edPrEP) in the Amsterdam PrEP demonstration project.

Methods
Participants could report daily about sex acts, PrEP use and condom use per partner type (steady and casual partners). We examined four strategies of PrEP and condom use: PrEP only, PrEP and condoms, condoms only, and neither strategy. We compared the proportions of sex acts per strategy between PrEP regimens. In 43 in-depth interviews, we explored motives for implementing each strategy.

Results
Three hundred and fifty-two participants reported 48 949 anal sex acts. PrEP only was the most common strategy employed with any partner type (81%, n = 39 650/48 949) and was motivated by anticipating more pleasurable sex, sexually transmitted infection’s perceived curability, and habituation to condomless sex. Combining PrEP and condoms was more often chosen for sex acts with casual partners (18%, n = 6829/37 317) than with steady partners (5%, n = 614/11 632) and was linked to, for example, higher perceived vulnerability for sexually transmitted infections or HIV and avoidance of PrEP disclosure. Condoms only was uncommon but occurred particularly among edPrEP users (4%, n = 379/8695). Applying neither strategy was common among edPrEP users with steady partners (25%, n = 538/2122) and was motivated by low perceived HIV risk.

Conclusion
Condoms remain a viable option for PrEP users in certain settings. Condoms were applied in higher risk settings, to avoid PrEP disclosure, or as substitute for PrEP, especially among edPrEP users.

Publication

Understanding pre-exposure prophylaxis (PrEP ) regimen use: Switching and discontinuing daily and event-driven PrEP among men who have sex with men“. Coyer, L., Van den Elshout, M.A.M., Achterbergh, R.C.A., Matser, A., Schim van der Loeff, M.F., Davidovich, U., De Vries, H.J.C., Prins, M., Hoornenborg, E., Boyd, A., Amsterdam PrEP team in the HIV Transmission Elimination Amsterdam (H-TEAM) Initiative. eClinicalMedicine 29(3):  100650, doi: 10.1016/j.eclinm.2020.100650.

Abstract
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.

Publication

Burden of living with HIV among men who have sex with men: a mixed-methods study“. Van Bilsen, W.P.H., Zimmermann, H.M.L., Boyd, A., Davidovich, U. for the HIV Transmission Elimination Amsterdam Initiative. Lancet HIV. 2020 Dec;7(12):e835-e843, doi: 10.1016/S2352-3018(20)30197-1.

Abstract

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.

Publication

“Decreased Time to Viral Suppression After Implementation of Targeted Testing and Immediate Initiation of Treatment of Acute Human Immunodeficiency Virus Infection Among Men Who Have Sex With Men in Amsterdam”. Dijkstra, M., van Rooijen, M.S., Hillebregt, M.M., van Sighem, A., Smith, C., Hogewoning, A., Davidovich, U., Heijman, T., Hoornenborg, E., Reiss, P., van der Valk, M., Prins, M., Prins, J.M., Schim van der Loeff, M.F., de Bree, G.J. for the HIV Transmission Elimination Amsterdam (H-TEAM) initiative. Clinical Infectious Diseases, ciaa505, doi: 10.1093/cid/ciaa505.

Abstract
Background

Men who have sex with men (MSM) with acute human immunodeficiency virus (HIV) infection (AHI) are a key source of new infections. To curb transmission, we implemented a strategy for rapid AHI diagnosis and immediate initiation of combination antiretroviral therapy (cART) in Amsterdam MSM. We assessed its effectiveness in diagnosing AHI and decreasing the time to viral suppression.

Methods

We included 63 278 HIV testing visits in 2008–2017, during which 1013 MSM were diagnosed. Standard of care (SOC) included HIV diagnosis confirmation in < 1 week and cART initiation in < 1 month. The AHI strategy comprised same-visit diagnosis confirmation and immediate cART. Time from diagnosis to viral suppression was assessed for 3 cART initiation periods: (1) 2008–2011: cART initiation if CD4 < 500 cells/μL (SOC); (2) January 2012–July 2015: cART initiation if CD4 < 500 cells/μL, or if AHI or early HIV infection (SOC); and (3a) August 2015–June 2017: universal cART initiation (SOC) or (3b) August 2015–June 2017 (the AHI strategy).

Results

Before implementation of the AHI strategy, the proportion of AHI among HIV diagnoses was 0.6% (5/876); after implementation this was 11.0% (15/137). Median time (in days) to viral suppression during periods 1, 2, 3a, and 3b was 584 (interquartile range [IQR], 267–1065), 230 (IQR, 132–480), 95 (IQR, 63–136), and 55 (IQR, 31–72), respectively (P < .001).

Conclusions

Implementing the AHI strategy was successful in diagnosing AHI and significantly decreasing the time between HIV diagnosis and viral suppression.

Publication

“Changes in mental health and drug use among men who have sex with men using daily and event-driven pre-exposure prophylaxis: Results from a prospective demonstration project in Amsterdam, the Netherlands”. Achterbergh, R.C.A., Hoornenborg, E., Boyd, A., Coyer, L., Meuzelaar, S.J.A., Hogewoning, A.A., Davidovich, U., van Rooijen, M.S., Schim van der Loeff, M.F., Prins, M., de Vries, H.J.C. EClinicalMedicine (2020), doi: 10.1016/j.eclinm.2020.100505.

Abstract

Background

Gay, bisexual and other men who have sex with men (GBMSM) are at increased risk of mental health disorders and drug use. In GBMSM taking pre-exposure prophylaxis (PrEP) for HIV, the proportion engaging in risk behaviors could increase due to decreased perception in HIV risk. In turn, this could leave them further susceptible to mental health disorders.

Methods

The AMsterdam PrEP study (AMPrEP) is a demonstration project offering a choice of daily PrEP or event-driven PrEP regimen at the STI clinic of the Public Health Service of Amsterdam. Eligible participants were HIV-negative GBMSM and transgender people at risk of HIV, aged ≥18 years. We assessed anxiety and depressive mood disorders (Mental Health Inventory 5), sexual compulsivity (Sexual Compulsivity Scale), alcohol use disorder (Alcohol Use Disorder Identification Test), and drug use disorder (Drug Use Disorder Identification Test) using yearly self-administered assessments (August 2015–September 2018). The proportion of mental health problems were analyzed and changes over time and between regimen were assessed using a logistic regression model. Variables associated with the development or recovery of disorders were assessed using a multistate Markov model.

Outcomes

Of 376 enrolled, we analyzed 341 participants with data at baseline and at least one follow-up visit. During a median follow-up of 2.5 years (IQR=2.3–2.7), the proportion assessed with sexual compulsivity decreased from 23% at baseline to 10% at the last visit (p<0.001) and drug use disorder decreased from 38% at baseline to 31% at the last visit (p = 0.004). No changes occurred in proportion assessed with anxiety/depressive mood disorders (20% at baseline, 18% at last visit, p = 0.358) or alcohol use disorder (28% at baseline, 22% at the last visit, p = 0.106). During follow-up, participants reported significant less use of alcohol (p<0.001), nitrites (p<0.001) and ecstasy (p<0.001). We found no differences between daily and event-driven PrEP users. The development and recovery of disorders during follow-up were highly interrelated.

Interpretation

Mental health disorders are prevalent among those initiating PrEP. We did not find increases in mental health disorders during PrEP use, but rather a decrease in sexual compulsivity and drug use disorders. The initial prevalence of mental health disorders in our study point at the continuous need to address mental health disorders within PrEP programs.

Funding

ZonMw, H-TEAM, Internal GGD research funds, Aidsfonds, Stichting AmsterdamDiner Foundation, Gilead Sciences, Janssen Pharmaceutica, M A C AIDS Fund, and ViiV Healthcare.

2019

Publication

“Is reaching 90-90-90 enough to end AIDS? Lessons from Amsterdam”. de Bree, G.J., van Sighem, A., Zuilhof, W., van Bergen, J.E.A.M., Prins, M., Heidenrijk, M., van der Valk, M., Brokx, P., Reiss, P. on behalf of the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative. Current Opinion in HIV and AIDS 14(6): 455-463, doi: 10.1097/COH.0000000000000586.

Abstract

Purpose of review

Although cities present opportunities for infectious pathogens such as HIV to spread, public health infrastructure within these cities also provides opportunities to design effective approaches to eliminate transmission of these pathogens. The HIV Transmission Elimination AMsterdam (H-TEAM) Initiative, a consortium of relevant stakeholders involved in HIV prevention and care, designed an integrated approach to curb the HIV epidemic in Amsterdam, including providing preexposure prophylaxis (PrEP), increasing awareness of acute HIV infection, offering same-day test and treat, and improving indicator disease-driven HIV testing.

Recent findings

In 2013, approximately 230 people in Amsterdam were newly diagnosed with HIV, largely belonging to one of two key affected populations, namely MSM and people with a migration background. Since the start of H-TEAM in 2014, a decrease in new diagnoses was observed (130 in 2017), with an increasing proportion of MSM who had been diagnosed with a recent infection.

Summary

The H-TEAM shows that a city-based concerted effort is feasible. However, major challenges remain, such as reducing the number of late HIV diagnoses, and identifying and providing appropriate services to a diminishing group of individuals who are likely the source of transmission.

Publication

“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”. Hoornenborg, E., Coyer, L., Achterbergh, R.C.A., Matser, A., Schim van der Loeff, M.F., Boyd, A., Van Duijnhoven, Y.T.H.P., Bruisten, S., Oostvogel, P., Davidovich, U., Hogewoning, A., Prins, M., De Vries, H.J.C., on behalf of the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam Initiative (H-TEAM). Lancet HIV 6(7): e447-e455, doi: 10.1016/S2352-3018(19)30136-5

Abstract

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.

Publication

“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”. Finkenflügel, R.N.N., Hoornenborg, E., Achterbergh, R.C.A., Marra, E., Davidovich, U., De Vries, H.J.C., Prins, M., Schim van der Loeff, M.F., on behalf of the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam Initiative (H-TEAM). Sexually Transmitted Diseases, 64(6): 400-406, doi: 10.1097/OLQ.0000000000000999

Abstract

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.

2018

Publication

“Change in sexual risk behaviour after 6 months of pre-exposure prophylaxis use: results from the Amsterdam pre-exposure prophylaxis demonstration project”. Hoornenborg, E., Coyer, L., van Laarhoven, A., Achterbergh, R.C.S., de Vries, H.J.C., Prins, M., Schim van der Loeff, M.F., on behalf of the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam Initiative (H-TEAM) (2018b). AIDS 2018, 32(11): 1527-1532, doi: 10.1097/QAD.0000000000001874

Abstract

Objective

HIV pre-exposure prophylaxis (PrEP) use may lead to higher STI incidence via behavioural risk compensation. We examined changes in sexual behaviour between baseline and 6 months after PrEP initiation among MSM and transgender women (TGW). Design: Prospective, open-label demonstration study at a large sexually transmitted infection (STI) clinic in Amsterdam, the Netherlands.

Methods

Participants answered questions about sexual behaviour in the preceding 3 months, including number of anal sex partners and frequency of anal sex with and without condom by partner type and were tested for STI. Sexual behaviour at baseline was compared with 6 months after PrEP initiation using Wilcoxon signed rank tests. Logistic regression was used to identify factors associated with an increase in receptive condomless anal sex acts (rCASa) with casual partners.

Results

Data were available for 328 (99%) MSM and 2 (1%) TGW. The number of receptive and insertive condomless anal sex acts (CASa) increased (baseline: median 11, interquartile range 4–23; 6 months: median 14, interquartile range 6–26, P<0.001), whereas the number of anal sex partners (P¼0.2) and anal sex acts (P¼0.8) remained unchanged. Prevalence of STI was stable. Older age, prior engagement in chemsex, recent use of postexposure prophylaxis and choosing a daily PrEP regimen at baseline were associated with an increase in rCASa with casual partners.

Conclusion

Over the first 6 months after initiation of PrEP, an increase in insertive and receptive CASa with casual partners was observed. Long-term follow-up data are needed and STI incidence needs to be closely monitored.

Publication

“Increasing awareness and prompting HIV testing: contributions of Amsterdam HIV Testing Week 2016”. den Haas, C., Meddens, E.M., van Bergen, J.E.A.M., de Bree, G.J., Hogewoning, A.A., Brinkman, K., de Wit, J.B.F., on behalf of the HIV Transmission Elimination AMsterdam initiative. International Journal of STD & AIDS 0(0): 1-9, doi: 10.1177/0956462418770014

Abstract

We evaluated Amsterdam HIV Testing Week (HTW) 2016 regarding its primary goals of raising awareness and prompting HIV testing. Participating services offered free, anonymous HIV testing, with a focus on reaching men who have sex with men (MSM) and people with a non-western migration background. Sociodemographic characteristics, HIV testing history, intention to test regularly, beliefs about personal risk and severity of HIV, and perceived social norms regarding HIV testing and people living with HIV were assessed among all who tested. A community quick scan assessed awareness of Amsterdam HTW 2016 and attitudes and intentions regarding HIV testing. Of 806 people tested, 59.6% (405/679) belonged to key populations. None tested HIV-positive and 37.6% intended to test regularly in the future. The com- munity quick scan found moderate awareness of Amsterdam HTW 2016. Awareness was highest among recent testers and HIV-positive MSM and not associated with HIV testing attitudes and intentions. People tested during Amsterdam HTW 2016 were from key populations and/or were not (adequately) reached via traditional testing approaches. The contribution of the Amsterdam HTW approach to raising awareness and prompting HIV testing in key populations may benefit from focusing on HIV-negative individuals who have not been tested recently.

Publication

“Men who have sex with men more often chose daily than event-driven use of pre-exposure prophylaxis: baseline analysis of a demonstration study in Amsterdam”. Hoornenborg, E., Achterbergh, R.C.A., Schim van der Loeff, M.F., Davidovich, U., Helm, J.J., Hogewoning, A., van Duijnhoven, Y.T.H.P., Sonder, G.J.B., de Vries, H.J.C., Prins, M., on behalf of the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam Initiative (2018a). Journal of the International Aids Society 21(3): e25105, doi: 10.1002/jia2.25105

Abstract

Introduction

The Amsterdam PrEP project is a prospective, open-label demonstration study at a large sexually transmitted infection (STI) clinic. We examined the uptake of PrEP; the baseline characteristics of men who have sex with men (MSM) and transgender persons initiating PrEP; their choices of daily versus event-driven PrEP and the determinants of these choices.

Methods

From August 2015 through May 2016, enrolment took place at the STI clinic of the Public Health Service of Amsterdam, the Netherlands. MSM or transgender persons were eligible if they had at least one risk factor for HIV infection within the preceding six months. Participants were offered a choice between daily or event-driven use of tenofovir/emtricitabine. Baseline data were analysed using descriptive statistics and multivariable analysis was employed to determine variables associated with daily versus event-driven PrEP.

Results

Online applications were submitted by 870 persons, of whom 587 were invited for a screening visit. Of them, 415 were screened for eligibility and 376 initiated PrEP. One quarter (103/376, 27%) chose event-driven PrEP. Prevalence of bacterial STI was 19.0% and mean condomless anal sex (CAS) episodes in the preceding three months were 11. In multivariable analysis, older age (≥45 vs. ≤34, aOR 2.1, 95% CI 1.2 to 3.9), being involved in a steady relationship (aOR 1.7, 95% CI 1.0 to 2.7), no other daily medication use (aOR 0.6, 95% CI 0.3 to 0.9), and fewer episodes of CAS (per log increase aOR 0.7, 95% CI 0.6 to 0.9) were determinants for choosing event-driven PrEP.

Discussion

PrEP programmes are becoming one of the more important intervention strategies with the goal of reducing incident HIV-infection and we were unable to accommodate many of the persons applying for this study. Offering a choice of dosing regimen to PrEP users may enable further personalization of HIV prevention strategies and enhance up-take, adherence and cost-effectiveness.

Conclusions

The majority of participants preferred daily versus event-driven use. Within this majority, a high number of CAS episodes before PrEP initiation was reported and we observed a high prevalence of STI. Determinants of choosing event-driven PrEP were older age, fewer CAS episodes, no other daily medication use, and involved in a steady relationship.

2017

Publication

“Acquisition of wild-type HIV-1 infection in a patient on pre-exposure prophylaxis with high intracellular concentrations of tenofovir diphosphate: a case report”. Hoornenborg, E., Prins, M., Achterbergh, R.C.A., Woittiez, L.R., Cornelissen, M., Jurriaans, S., Kootstra, N.A., Anderson, P.L., Reiss, P., de Vries, H.C.J., Prins, J.M., de Bree, G.J., on behalf of the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam Initiative (H-TEAM) (2017b). Lancet HIV 4(11): E522-E528, doi: 10.1016/S2352-3018(17)30132-7

Abstract

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.

Publication

“HIV testing week 2015: lowering barriers for HIV testing among high-risk groups in Amsterdam”. Bartelsman, M., Joore, I.K., van Bergen, J.E., Hogewoning, A.A., Zuure, F.R., van Veen, M.G., on behalf of the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative (2017) BMC Infectious Diseases 17: 529, doi: 10.1186/s12879-017-2617-0

Abstract

Background

Evaluation of the HIV Testing Week (HTW) 2015 in Amsterdam: the number of (positive) tested persons, characteristics and testing history of the tested population, the differences in attendance per location and the healthcare workers’ experiences and opinions concerning the HTW.

Methods

The HTW took place from 28 November till 4 December 2015. Anonymous HIV rapid testing (INSTI™ HIV1/HIV2 Ab test or Determine™ HIV-1/2 Ag/Ab test) was offered free of charge at four hospitals, 12 general practitioner (GP) clinics, a sexually transmitted infections (STI) clinic, a laboratory, sites of a community-based organisation, and at outreach locations. Home-based testing (OraQuick® In-Home HIV Test) was offered online. The focus was to motivate two groups to test: men who have sex with men (MSM) and non-Western migrants. Questionnaires regarding participant’s characteristics and HIV testing history were collected. Also healthcare workers were asked to complete a questionnaire evaluating the HTW.

Results

In total, 1231 participants were tested. With three positive HIV tests, the detection rate was 0.3% (95%CI 0.26–0.37). Of all participants, 24.7% (304/1231) were MSM. Respectively, 22.3% (275/1231) and 15.7% (193/1231) were first- and second-generation migrants from a non-Western country. Altogether, 56.7% (698/1231) of participants belonged to one of the targeted risk groups. For 32.7% (402/1231) of participants, it was the first time they received testing, and 35.1% (432/1231) were tested more than 1 year ago. Among MSM 13.2% were tested for the first time, among first- and second-generation non-Western migrants this percentage was significantly higher at 27.2% and 33.5% respectively (p < 0.01). The number of tested participants per location varied widely, especially between GP clinics (range 3–63). Healthcare workers were positive about the HTW: about half (46.2%) stated they would more readily offer an HIV test following their experience with the HTW.

Conclusions

This was the first time the Amsterdam HTW was organised on such a large scale. The majority of the tested population belonged to one of the targeted risk groups and received testing either for the first time or for the first time in over a year. It is important to further build upon the experiences of the HTW and offer free of charge low-threshold HIV testing more structurally. An evaluation of cost-effectiveness is also warranted for future editions of the HTW.

Publication

“Development and validation of a risk score to assist screening for acute HIV-1 infection among men who have sex with men”. Dijkstra, M., de Bree, G.J., Stolte, I.G., Davidovich, U., Sanders, E.J., Prins, M., Schim van der Loef, M.F. (2017). BMC Infectious Diseases 17(1): 425, doi: 10.1186/s12879-017-2508-4

Abstract

Background

Early treatment of acute HIV-1 infection (AHI) is beneficial for patients and could reduce onward transmission. However, guidelines on whom to test for AHI with HIV-1 RNA testing are lacking.

Methods

A risk score for possible AHI based on literature and expert opinion – including symptoms associated with AHI and early HIV-1 – was evaluated using data from the Amsterdam Cohort Studies among men who have sex with men (MSM). Subsequently, we optimized the risk score by constructing two multivariable logistic regression models: one including only symptoms and one combining symptoms with known risk factors for HIV-1 seroconversion, using generalized estimating equations. Several risk scores were generated from these models and the optimal risk score was validated using data from the Multicenter AIDS Cohort Study.

Results

Using data from 1562 MSM with 175 HIV-1 seroconversion visits and 17,271 seronegative visits in the Amsterdam Cohort Studies, the optimal risk score included four symptoms (oral thrush, fever, lymphadenopathy, weight loss) and three risk factors (self-reported gonorrhea, receptive condomless anal intercourse, more than five sexual partners, all in the preceding six months) and yielded an AUC of 0.82. Sensitivity was 76.3% and specificity 76.3%. Validation in the Multicenter AIDS Cohort Study resulted in an AUC of 0.78, sensitivity of 56.2% and specificity of 88.8%.

Conclusions

The optimal risk score had good overall performance in the Amsterdam Cohort Studies and performed comparable (but showed lower sensitivity) in the validation study. Screening for AHI with four symptoms and three risk factors would increase the efficiency of AHI testing and potentially enhance early diagnosis and immediate treatment.

Publication

“MSM starting pre-exposure prophylaxis are at risk of hepatitis C virus infection”. Hoornenborg, E., Achterbergh, R.C.A., Schim van der Loeff, M.F., Davidovich, U., Hogewoning, A., de Vries, H.J.C., Schinkel, J., Prins, M., van de Laar, T.J.W., on behalf of the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam Initiative (H-TEAM) & MOSAIC study group (2017a). AIDS 31(11): 1603-1610, doi: 10.1097/QAD.0000000000001522

Abstract

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.