“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.
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.
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.
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.
“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
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.
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.
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.
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.
“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
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.
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.
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.
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.
“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
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.
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.
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.
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.
“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
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.
“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
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.
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.
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.
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.
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.
“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
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.
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.
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.
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.
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.
“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
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.
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.
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.
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.
“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
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.
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.
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%.
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.
“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
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.
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.
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.
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.