Background
Daily and event-driven HIV pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine is highly effective to prevent HIV in men who have sex with men (MSM). PrEP care generally ...consists of in-clinic monitoring every 3 months that includes PrEP dispensing, counseling, and screening for HIV and sexually transmitted infections (STIs). However, the optimal frequency for monitoring remains undetermined. Attending a clinic every 3 months for monitoring may be a barrier for PrEP. Online-mediated PrEP care and reduced frequency of monitoring may lower this barrier.
Objective
The primary objective of this study is to establish the noninferiority of online PrEP care (vs in-clinic care) and monitoring every 6 months (vs every 3 months). The secondary objectives are to (1) examine differences between PrEP care modalities regarding incidences of STIs, HIV infection, and hepatitis C virus infection; retention in PrEP care; intracellular tenofovir-diphosphate concentration; and satisfaction, usability, and acceptability of PrEP care modalities; and (2) evaluate associations of these study outcomes with sociodemographic, behavioral, and psychological characteristics.
Methods
This study is a 2×2 factorial, 4-arm, open-label, multi-center, randomized, controlled, noninferiority trial. The 4 arms are (1) in-clinic monitoring every 3 months, (2) in-clinic monitoring every 6 months, (3) online monitoring every 3 months, and (4) online monitoring every 6 months. The primary outcome is a condomless anal sex act with a casual partner not covered or insufficiently covered by PrEP (ie, “unprotected act”) as a proxy for HIV infection risk. Eligible individuals are MSM, and transgender and gender diverse people aged ≥18 years who are eligible for PrEP care at 1 of 4 participating sexual health centers in the Netherlands. The required sample size is 442 participants, and the planned observation time is 24 months. All study participants will receive access to a smartphone app, which contains a diary. Participants are requested to complete the diary on a daily basis during the first 18 months of participation. Participants will complete questionnaires at baseline and 6, 12, 18, and 24 months. Dried blood spots will be collected at 6 and 12 months for assessment of intracellular tenofovir-diphosphate concentration. Incidence rates of unprotected acts will be compared between the online and in-clinic arms, and between the 6-month and 3-month arms. Noninferiority will be concluded if the upper limit of the 2-sided 97.5% CI of the incidence rate ratio is <1.8.
Results
The results of the main analysis are expected in 2024.
Conclusions
This trial will demonstrate whether online PrEP care and monitoring every 6 months is noninferior to standard PrEP care in terms of PrEP adherence. If noninferiority is established, these modalities may lower barriers for initiating and continuing PrEP use and potentially reduce the systemic burden for PrEP providers.
Trial Registration
ClinicalTrials.gov NCT05093036; https://tinyurl.com/28b8ndvj
International Registered Report Identifier (IRRID)
DERR1-10.2196/51023
Pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV infections, but is not yet implemented in the Netherlands. As the attitudes of health-care professionals toward PrEP can ...influence future PrEP implementation, we studied PrEP knowledge and beliefs and their association with PrEP acceptability among professionals in clinics for sexually transmitted infection (STI professionals) and HIV treatment centers (HIV specialists). In addition, we examined preferred regimens, attitudes toward providing PrEP to key populations and to reimbursement of PrEP costs.
An online questionnaire was distributed among 24 public health STI clinics and 27 HIV treatment centers nationwide in the Netherlands between January and August 2015. The acceptability of PrEP was measured on a 7-point Likert scale ranging from 1 = low to 7 = high acceptability. Univariable and multivariable linear regression analyses were used to explore associations between demographic characteristics, PrEP knowledge, beliefs about PrEP, and PrEP acceptability.
In total, 209 people (143 STI professionals and 66 HIV specialists) completed the questionnaire. The mean acceptability of PrEP implementation was 4.28 (SD 1.68) among STI professionals and 4.42 (SD 1.67) among HIV specialists. The mean score on self-perceived knowledge related to PrEP efficacy was 3.90 (SD 1.57) among STI professionals and 5.68 (SD 1.08) among HIV specialists (
-value of <0.001). Beliefs associated with lower PrEP acceptability among both groups were the fear that PrEP use will lead to a decrease in condom use and an increase in STI, the high costs of PrEP and ethical issues regarding prescribing antiretroviral medication to healthy individuals. No preference for a daily or an event-driven regimen was detected. Most participants deemed the following groups to be eligible for PrEP: men who have sex with men (MSM) who regularly get post-exposure prophylaxis, MSM who never used condoms with casual partners and MSM with an HIV-positive partner with a detectable viral load. Over half of the participants indicated that PrEP users should partly (54.1%) or fully (35.4%) pay the costs of PrEP.
In 2015, PrEP acceptability was only moderate among Dutch STI professionals and HIV specialists, which is far from an optimal setting. Addressing barriers to PrEP acceptability in educational programs for various types of health-care professionals is needed to successfully implement PrEP in the Netherlands.
To examine whether drug users (DU) in the Amsterdam Cohort Study (ACS) are still at risk for HIV, we studied trends in HIV incidence and injecting and sexual risk behaviour from 1986 to 2011.
The ACS ...is an open, prospective cohort study on HIV. Calendar time trends in HIV incidence were modelled using Poisson regression. Trends in risk behaviour were modelled via generalized estimating equations. In 2010, a screening for STI (chlamydia, gonorrhoea and syphilis) was performed. Determinants of unprotected sex were studied using logistic regression analysis.
The HIV incidence among 1298 participants of the ACS with a total follow-up of 12,921 person-years (PY) declined from 6.0/100 PY (95% confidence interval CI 3.2-11.1) in 1986 to less than 1/100 PY from 1997 onwards. Both injection and sexual risk behaviour declined significantly over time. Out of 197 participants screened for STI in 2010-2011, median age 49 years (IQR 43-59), only 5 (2.5%) were diagnosed with an STI. In multivariable analysis, having a steady partner (aOR 4.1, 95% CI 1.6-10.5) was associated with unprotected sex. HIV-infected participants were less likely to report unprotected sex (aOR 0.07, 95% CI 0.02-0.37).
HIV incidence and injection risk behaviour declined from 1986 onwards. STI prevalence is low; unprotected sex is associated with steady partners and is less common among HIV-infected participants. These findings indicate a low transmission risk of HIV and STI, which suggests that DU do not play a significant role in the current spread of HIV in Amsterdam.
A key unsolved question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of acquired immunity. Insights from infections with the four seasonal human coronaviruses might ...reveal common characteristics applicable to all human coronaviruses. We monitored healthy individuals for more than 35 years and determined that reinfection with the same seasonal coronavirus occurred frequently at 12 months after infection.
Abstract
CD1d-restricted NKT cells express an invariant TCR and have been demonstrated to play an important regulatory role in a variety of immune responses. Invariant NKT cells down-regulate ...autoimmune responses by production of type 2 cytokines and can initiate antitumor and antimicrobial immune responses by production of type 1 cytokines. Although defects in the (invariant) Vα24+Vβ11+ NKT cell population have been observed in patients with cancer and autoimmune diseases, little is known regarding the protective role of Vα24+Vβ11+ NKT cells in human infectious disease. In a cross-sectional study in HIV-1-infected individuals, we found circulating numbers of Vα24+Vβ11+ NKT cells to be reduced, independent of CD4+ T cell counts, CD4:CD8 ratios, and viral load. Because a small minority of Vα24+Vβ11+ NKT cells of healthy donors expressed HIV-1 (co)receptors and the vast majority of Vα24+Vβ11+ NKT cells in HIV-1-infected individuals expressed the Fas receptor, the depletion was more likely due to Fas-mediated apoptosis than to preferential infection of Vα24+Vβ11+ NKT cells by HIV-1. A longitudinal cohort study, in which patients were analyzed before seroconversion and 1 and 5 years after seroconversion, demonstrated that a large proportion of the depletion occurred within the first year postseroconversion. In this longitudinal study no evidence was found to support an important role of Vα24+Vβ11+ NKT cells in determining the rate of progression during HIV-1 infection.
Background Many individuals with hepatitis C virus (HCV) infection are undiagnosed. Purpose This study describes the development and the use and outcomes of a mass media campaign, combined with an ...Internet risk assessment and an Internet-mediated blood-testing procedure for HCV to identify individuals infected with HCV in the general population. Methods From April 2007 to December 2008, individuals in HCV risk groups were referred to an online, previously validated risk-assessment questionnaire at www.heptest.nl . Individuals at risk could download a referral letter for a free, anonymous HCV blood test in a nonclinical setting. Test results could be obtained online, 1 week later, using a personal log-in code. Anti-HCV-positive participants were requested to visit the Public Health Service for confirmation and RNA testing. Chronically HCV-infected individuals were referred for treatment. Data were analyzed in 2009–2010. Results The website attracted 40,902 visitors. Of the 9653 who completed the questionnaire, 2553 were at risk for HCV (26.4%). Main reported risk factors were a blood transfusion prior to 1992 and noninjecting drug use. Of the 1480 eligible for the blood test, 420 opted for testing (28%). HCV antibodies were detected in 3.6% ( n =15, 95% CI=2.1%, 5.7%); of the 12 with a chronic HCV infection, six began treatment. Conclusions Internet-mediated risk-based testing for HCV has proved to be a feasible and effective strategy to identify undiagnosed HCV infection in the general population. All HCV-infected individuals belonged to hard-to-reach populations. Test uptake was 28%, which is high for an online project that includes blood testing. Because Internet-mediated testing is low-cost, this strategy holds promise for future screening.
Hepatitis C virus (HCV) is mainly transmitted by exposure to infected blood, and can lead to liver cirrhosis and liver cancer. Since the onset of HCV and the development of liver cirrhosis usually ...are asymptomatic, many HCV-infected individuals are still undiagnosed. To identify individuals infected with HCV in the general population, a low threshold, internet-mediated blood testing service was set up. We performed a qualitative study examining reasons for compliance and noncompliance with advice to test for HCV via the online blood testing service.
Semistructured telephone interviews were conducted with 33 website visitors who had been advised to test for HCV (18 testers, 15 non-testers). Transcribed interviews were analyzed qualitatively and interpreted using psychosocial theories of health behavior.
Reasons for testing pertaining to the online service were: the testing procedure is autonomous, personalized test advice is provided online, reminder emails are sent, and there is an online planning tool. Reasons for testing not specific to the online service were: knowing one's status can prevent liver disease and further transmission of HCV, HCV is curable, testing can provide reassurance, physical complaints are present, and there is liver disease in one's social environment. Service-related reasons for not testing pertained to inconvenient testing facilities, a lack of commitment due to the low threshold character of the service, computer/printing problems, and incorrectly interpreting an online planning tool. The reasons for not testing that are not specific to the online service were: the belief that personal risk is low, the absence of symptoms, low perceived urgency for testing and treatment, fear of the consequences of a positive test result, avoiding threatening information, and a discouraging social environment.
Features specific to the online service played a significant role in motivation to test for HCV above and beyond the more conventional perceived health benefits of HCV testing. However, some online specific features were considered problematic and need to be adapted. Methods and strategies for dealing with these impeding factors and for improving compliance with testing via the online service are outlined.
Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. Individuals from the ...Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 ...L between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up PYFU) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/...L. A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/...L among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval CI, 20.0-21.1 per 1000 PYFU) with current CD4 200-349 cells/...L to 4.1 per 1000 PYFU (95% CI, 3.6-4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/...L. Persons with a current CD4 of 500-749 cells/...L had a significantly higher rate of ADIs (adjusted incidence rate ratio aIRR, 1.20; 95% CI, 1.10-1.32), whereas those with a current CD4 of ≥1000 cells/...L had a similar rate (aIRR, 0.92; 95% CI, .79-1.07), compared to a current CD4 of 750-999 cells/...L. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25-1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01-1.25), comparing persons with a current CD4 of 500-749 cells/...L to 750-999 cells/...L. The incidence of ADIs was higher in individuals with a current CD4 count of 500-749 cells/...L compared to those with a CD4 count of 750-999 cells/...L, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/... (ProQuest: ... denotes formulae/symbols omitted.)
Background and aims
Major declines in HIV and hepatitis C and B virus (HCV/HBV) incidence among people who inject drugs (PWID) have been attributed to early implementation of harm‐reduction programs ...(HRP) in the Netherlands, but alternative factors such as selective mortality and demographic and drug market shifts over time probably contributed to observed incidence declines. We quantified and tested the effect of HRP participation on risk of these infections among PWID in Amsterdam, the Netherlands.
Design
We emulated the design of a hypothetical, ideal randomized trial using observational data from the Amsterdam Cohort Studies (1985–2014).
Setting
Amsterdam, the Netherlands.
Participants
We included PWID who ever used opioids, had a recent history of injecting drug use (IDU) and tested negative for HIV, HCV or HBV. Of 983 participants, 640, 137 and 308 were included for the HIV, HCV and HBV analyses and 59, 45 and 49 seroconversions were observed, respectively.
Interventions
Intervention arms were: complete HRP participation ≥ 60 mg/day methadone and 100% needle and syringe program (NSP) coverage, or any methadone dose if no recent injection drug use versus no HRP and partial HRP participation combined (< 60 methadone mg/day and/or < 100% NSP coverage).
Conclusions
Complete participation in harm reduction programs appears to have led to substantial decreases in HIV and hepatitis C and B virus acquisition risk among people who inject drugs in the Netherlands.
Measurements
Separately for each infection, we estimated the hazard ratios (HR) comparing HRP arms using marginal structural models.
Findings
Compared with no/partial HRP participation, complete HRP participation led to lower risk of HIV HR = 0.54, 95% confidence interval (CI) = 0.27–1.08, HCV (HR = 0.16, 95% CI = 0.06–0.40) and HBV (HR = 0.28, 95% CI = 0.13–0.61) acquisition.
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