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

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

Mpox outbreak in the Netherlands, 2022: public health response, characteristics of the first 1,000 cases and protection of the first-generation smallpox vaccine.

In early May 2022, a global outbreak of mpox started among persons without travel history to regions known to be enzootic for monkeypox virus (MPXV). On 8 August 2022, the Netherlands reported its 1,000th mpox case, representing a cumulative incidence of 55 per million population, one of the highest cumulative incidences worldwide. We describe characteristics of the first 1,000 mpox cases in the Netherlands, reported between 20 May and 8 August 2022, within the context of the public health response. These cases were predominantly men who have sex with men aged 31-45 years. The vast majority of infections were acquired through sexual contact with casual partners in private or recreational settings including LGBTQIA+ venues in the Netherlands. This indicates that, although some larger upsurges occurred from point-source and/or travel-related events, the outbreak was mainly characterised by sustained transmission within the Netherlands. In addition, we estimated the protective effect of first-generation smallpox vaccine against moderate/severe mpox and found a vaccine effectiveness of 58% (95% CI: 17-78%), suggesting moderate protection against moderate/severe mpox symptoms on top of any possible protection by this vaccine against MPXV infection and disease. Communication with and supporting the at-risk population in following mitigation measures remains essential.

HIV-1-infection in a man who has sex with men despite self-reported excellent adherence to pre-exposure prophylaxis, the Netherlands, August 2021: be alert to emtricitabine/tenofovir-resistant strain transmission.

In August 2021, a man who has sex with men was diagnosed with HIV-1 infection despite using event-driven pre-exposure prophylaxis for over 2 years with self-reported excellent adherence. Sequencing identified resistance-associated mutations (RAM) M184V and K65R, conferring resistance to emtricitabine and tenofovir, and RAM V108I and E138A. Background RAM prevalence was two of 164 (1.2%) new HIV diagnoses in Amsterdam (2017-19). We reiterate the need for frequent HIV testing among PrEP users and additional testing in case of symptoms.

Increasing trends of lymphogranuloma venereum among HIV-negative and asymptomatic men who have sex with men, the Netherlands, 2011 to 2017.

IntroductionLymphogranuloma venereum (LGV), an invasive form of Chlamydia trachomatis infection, has been reported among (mainly HIV-positive) men who have sex with men (MSM) since 2003. In the Netherlands, LGV testing recommendations changed from selective to universal testing in 2015. Changes in tested populations could have led to incomparable LGV positivity rates over time.AimWe investigated LGV trends among MSM attending Centres for Sexual Health using surveillance data between 2011 and 2017.MethodsLGV positivity was calculated among MSM tested for rectal Chlamydia infection and MSM tested specifically for LGV. With multivariable logistic regression analysis, the association between years and LGV was adjusted for testing indicators and determinants.ResultsWe included 224,194 consultations. LGV increased from 86 in 2011 to 270 in 2017. Among LGV-positives, proportions of HIV-negative and asymptomatic MSM increased from 17.4% to 45.6% and from 31.4% to 49.3%, respectively, between 2011 and 2017. Among MSM tested for rectal chlamydia, LGV positivity increased from 0.12% to 0.33% among HIV-negatives and remained stable around 2.5% among HIV-positives. Among LGV-tested MSM, LGV positivity increased from 2.1% to 5.7% among HIV-negatives and from 15.1% to 22.1% among HIV-positives. Multivariable models showed increased odds ratios and significant positive associations between years and LGV.ConclusionsAlthough increased testing and changes in LGV incidence are difficult to disentangle, we found increasing LGV trends, especially when corrected for confounding. LGV was increasingly attributed to HIV-negative and asymptomatic MSM, among whom testing was previously limited. This stresses the importance of universal testing and continuous surveillance.

Integrating hepatitis B, hepatitis C and HIV screening into tuberculosis entry screening for migrants in the Netherlands, 2013 to 2015.

We evaluated uptake and diagnostic outcomes of voluntary hepatitis B (HBV) and C virus (HCV) screening offered during routine tuberculosis entry screening to migrants in Gelderland and Amsterdam, the Netherlands, between 2013 and 2015. In Amsterdam, HIV screening was also offered. Overall, 54% (461/859) accepted screening. Prevalence of chronic HBV infection (HBsAg-positive) and HCV exposure (anti-HCV-positive) in Gelderland was 4.48% (9/201; 95% confidence interval (CI): 2.37-8.29) and 0.99% (2/203; 95% CI: 0.27-3.52), respectively, all infections were newly diagnosed. Prevalence of chronic HBV infection, HCV exposure and chronic HCV infection (HCV RNA-positive) in Amsterdam was 0.39% (1/256; 95% CI: 0.07-2.18), 1.17% (3/256; 95% CI: 0.40-3.39) and 0.39% (1/256; 95% CI: 0.07-2.18), respectively, with all chronic HBV/HCV infections previously diagnosed. No HIV infections were found. In univariate analyses, newly diagnosed chronic HBV infection was more likely in participants migrating for reasons other than work or study (4.35% vs 0.83%; odds ratio (OR) = 5.45; 95% CI: 1.12-26.60) and was less likely in participants in Amsterdam than Gelderland (0.00% vs 4.48%; OR = 0.04; 95% CI: 0.00-0.69). Regional differences in HBV prevalence might be explained by differences in the populations entering compulsory tuberculosis screening. Prescreening selection of migrants based on risk factors merits further exploration.

Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015.

Resistance of Neisseria gonorrhoeae to azithromycin and ceftriaxone has been increasing in the past years. This is of concern since the combination of these antimicrobials is recommended as the first-line treatment option in most guidelines. To analyse trends in antimicrobial resistance, we retrospectively selected all consultations with a positive N. gonorrhoeae culture at the sexually transmitted infection clinic, Amsterdam, the Netherlands, from January 2012 through September 2015. Minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone were analysed per year, and determinants associated with decreased susceptibility to azithromycin (MIC > 0.25 mg/L) or ceftriaxone (MIC > 0.032 mg/L) were assessed. Between 2012 and 2015 azithromycin resistance (MIC > 0.5 mg/L) was around 1.2%, the percentage of isolates with intermediate MICs (> 0.25 and ≤ 0.5 mg/L) increased from 3.7% in 2012, to 8.6% in 2015. Determinants associated with decreased azithromycin susceptibility were, for men who have sex with men (MSM), infections diagnosed in the year 2014, two infected sites, and HIV status (HIV; associated with less decreased susceptibility); for heterosexuals this was having ≥ 10 sex partners (in previous six months). Although no ceftriaxone resistance (MIC > 0.125 mg/L) was observed during the study period, the proportion of isolates with decreased ceftriaxone susceptibility increased from 3.6% in 2012, to 8.4% in 2015. Determinants associated with decreased ceftriaxone susceptibility were, for MSM, infections diagnosed in 2014, and pharyngeal infections; and for heterosexuals, infections diagnosed in 2014 or 2015, being of female sex, and having ≥ 10 sex partners. Continued decrease of azithromycin and ceftriaxone susceptibility will threaten future treatment of gonorrhoea. Therefore, new treatment strategies are warranted.

Sexualized drug use and STD and HIV incidence among men who have sex with men in Amsterdam, the Netherlands.

BACKGROUND: We assessed the association between sexualized drug use (SDU), and incident sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV) infections among men who have sex with men (MSM). METHODS: We used data from the MS2 cohort study, conducted at the STI Outpatient Clinic of the Public Health Service of Amsterdam, the Netherlands, in 2014-2019. Eligible participants were adult HIV-negative MSM with ≥2 STDs in the preceding year and MSM living with HIV and ≥1 STD. Participation encompassed 3-monthly visits including STD screening and questionnaires on drug use. Primary outcomes were incident HIV, anal chlamydia/gonorrhoea, and syphilis. We studied the association between SDU of individual drugs and incident HIV and STDs, using Poisson regression. Analyses were adjusted for age and HIV-status. RESULTS: 131 HIV-negative MSM and 173 MSM living with HIV were included for analysis. SDU with GHB/GBL (aIRR = 7.2, 95% CI = 1.4-35.5) in the 3 months before testing was associated with incident HIV. SDU with GHB/GBL (aIRR = 1.2, 95% CI = 1.0-1.4), ketamine (aIRR = 1.3, 95% CI = 1.0-1.6) or methamphetamine (aIRR = 1.3, 95% CI = 1.0-1.6) was associated with incident anal chlamydia/gonorrhoea. We found no association between SDU with specific drug types and syphilis incidence. CONCLUSIONS: SDU with GHB/GBL, ketamine and methamphetamine among MSM was associated with incident HIV and anal chlamydia/gonorrhoea. HIV-negative MSM engaging in SDU should be advised to use HIV pre-exposure prophylaxis, and all MSM engaging in SDU should be advised to have STD screening regularly. We suggest counselling on STDs among MSM engaging in SDU.

Clinical pattern and treatment outcome of Cutaneous Leishmaniasis in two hospitals in Bahir Dar, Ethiopia (2017-2021).

INTRODUCTION: Cutaneous Leishmaniasis (CL) in Ethiopia is caused by a unique species, L. aethiopica. In Ethiopia, there are limited studies that provide detailed clinical descriptions of CL, treatment options, and treatment outcomes. METHODOLOGY: We conducted a descriptive study based on routinely collected data in medical files from two hospitals in Bahir Dar, Ethiopia, from 2017 to 2021. Three months following the end of therapy, we retrieved sociodemographic and clinical data, as well as data on the treatment outcome. RESULTS: Between March 2017 and June 2021, 94 patients were diagnosed with CL at the two hospitals. Of those, 46 (48.9%) of individuals had localized CL, 36 (38.3%) mucocutaneous leishmaniasis (MCL), and 12 (12.8%) diffuse CL. Sixty-five (69.1%) of the participants were men. The most prevalent morphologic appearances were plaque (n = 42, 46.2%), nodule (n = 38, 41.8%), infiltrative (n = 34, 36.2%), crusted (n = 32, 34%), and ulcerated (n = 24, 25.5%). Scarred, volcanic, and patchy lesions were also documented. Systemic pentavalent antimonials were the most common treatment (n = 55, 58.5%), curing 21/38 (55%) of the patients. Pentavalent antimonials were also given intralesionally to seventeen patients (18.1%), with 15/16 (94%) of them being cured. Overall, 61% (40/66) of patients with documented treatment outcomes were cured. CONCLUSIONS: As CL in Ethiopia has a wide array of clinical presentations, clinicians should be suspicious of patients from endemic areas who present with dermatologic manifestations. Physicians can employ local treatment as a first line before resorting to systemic therapy.

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

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

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

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

"Stopping the itch": mass drug administration for scabies outbreak control covered for over nine million people in Ethiopia.

INTRODUCTION: In 2018, the Ethiopian Ministry of Health embarked on a Mass Drug Administration (MDA) campaign that involved over 9 million people in Ethiopia - the largest scabies MDA campaign ever conducted on a global level. We describe its implementation and report on a) numbers screened and identified with scabies, b) treatment category and drug type and c) human resources used, duration, and cost of the campaign. METHODOLOGY: The MDA campaign was conducted according to national guidelines and activities including: planning and organization, engagement of local leaders, community mobilisation and advocacy, awareness-raising among health workers, field implementation, and monitoring and evaluation. The campaign was conducted between July and August 2018. RESULTS: The MDA campaign was implemented by about 15,000 people, mostly from the community, over an average of 6 days and reached 9, 057, 427 people. A total of 875,890 (9.7%) scabies cases were detected and 995,471 (11.0%) contacts received treatment. (Contact-to-case ratio = 1.3). Scabies prevalence varied, the highest prevalence was seen in Central Gondar (39.2%), South Gondar (16.7%) and North Gondar (15.0%), these neighbouring zones contributing more than two third of all scabies cases in the region. Of 1,738,304 (93%) who received treatment, 94% received ivermectin, the rest topical permethrin and sulfur. The average coverage capacity of an MDA campaign staff member was 84 people per day. The total cost was 11,696,333 United States Dollars (USD). Cost per 100,000 population = 129,135 USD. CONCLUSIONS: This experience of rapid-large scale implementation would be useful to scale up similar interventions and "stop the itch" in other regions of Ethiopia.

Does mass drug administration for community-based scabies control works? The experience in Ethiopia.

INTRODUCTION: After a scabies outbreak in Amhara Region, Ethiopia in 2015/2016, the Regional Health Bureau performed an extensive Mass Drug Administration (MDA). In May 2017, we collected data to assess the impact of the treatment on the scabies control. METHODOLOGY: We retrieved baseline data from the 2015/16 burden assessment: campaign organization and administration information. We did a community based cross-sectional study using a structured questionnaire on disease and treatment history plus the presence or absence of active scabies in three Zones. We selected households using stratified random sampling deployed 7581 questionnaires and performed key informant interviews. RESULTS: 46.3% had a previous scabies diagnosis in the last 2 years of which 86.1% received treatment, and the cure rate was 90.6%. Fifteen months after intervention the scabies prevalence was 21.0 % (67.3% new cases and 32.7% recurrences). The highest burden of new cases (93.1%) was found in the North Gondar zone. The likelihood of treatment failure was higher for treatments offered in clinics (12.2%) as opposed to via the campaign (7.9%). Failure to follow the guidelines, shortage of medicine and lack of leadership prioritization were identified as reasons for resurgence of the disease. CONCLUSIONS: We demonstrated that community engagement is essential in the success of scabies MDA, alongside strong political commitment, and guideline adherence. Effectiveness and sustainability of the MDA was compromised by the failing of proper contact treatment, surveillance and case management.

Motives for choosing, switching and stopping daily or event-driven pre-exposure prophylaxis - a qualitative analysis.

INTRODUCTION: In settings where both daily and event-driven pre-exposure prophylaxis (PrEP) are offered to men who have sex with men (MSM), a clear understanding of the motives to choose between the different dosing-regimens can facilitate more effective PrEP implementation. We therefore studied the motives for choosing for, switching between, and stopping daily or event-driven PrEP. METHODS: We used data (August 2015-June 2017) from the prospective, longitudinal, open-label Amsterdam PrEP demonstration study, in which daily (dPrEP) and event-driven PrEP (edPrEP) were offered to 374 HIV-negative MSM and two transgender persons. Participants self-selected the preferred PrEP-regimen at baseline and could switch regimens at three-monthly follow-up visits. We measured motives for choosing PrEP-regimen at baseline and for switching and stopping PrEP at follow-up visits. Open- and closed-end items were combined and qualitatively analysed. RESULTS: Choices of PrEP-regimens were determined by personal and contextual factors, involving the perceived self-efficacy concerning adherence, the risk-context, and the anticipated impact of PrEP on physical and sexual wellbeing. dPrEP was preferred because of the anticipated better adherence and the fear of side-effects relating to edPrEP re-initiations. Moreover, dPrEP was perceived to be more effective than edPrEP. Motives to choose edPrEP were the expected physical burden of dPrEP, anticipated side-effects of dPrEP, and fear to forget daily doses. Regarding the risk-context: dPrEP was preferred for unplanned and/or frequent sex, while edPrEP was chosen when risk was predictable and/or less frequent. While some chose for dPrEP to gain more sexual freedom, others chose for edPrEP to minimize sexual risk episodes. Changes in the above factors, such as changing risk patterns, changing relationships or changing physical conditions, resulted in switching regimens. Choices to stop PrEP were related to lower sexual risk, adherence issues and side-effects. CONCLUSIONS: The great diversity of motives illustrates the importance of offering a choice of PrEP-regimens. In counselling of MSM starting PrEP, choices for PrEP-regimens may be addressed as a continuum of flexible and changeable options over time. This may help individuals choose the PrEP-regimen that best fits their current sexual context, priorities and personal capabilities and therefore will be more easily adhered to.

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.

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.