Online mediated HIV pre-exposure prophylaxis care and reduced monitoring frequency for men who have sex with men: protocol of the EZI-PrEP study - a randomized controlled non-inferiority trial (Preprint)

Abstract

Daily and event-driven HIV pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine is highly effective to prevent acquisition of HIV in men who have sex with men (MSM). PrEP care generally consists of 3-monthly in-clinic monitoring visits that include PrEP dispensing, counselling and screening for HIV and sexually transmitted infections (STIs). However, the optimal monitoring frequency remains undetermined. Moreover, attending a clinic for PrEP care and the 3-monthly monitoring schedule may be barriers for PrEP use. Online-mediated PrEP care and reduced monitoring frequency may lower these barriers.

The primary objective of this study is to establish non-inferiority of online PrEP care (vs. in-clinic care) and 6-monthly monitoring (vs. 3-monthly monitoring). The secondary objective are (1) to examine differences between PrEP care modalities regarding incidence of STIs, HIV and hepatitis C virus infection, retention in PrEP care, intracellular tenofovir-diphosphate concentration, and satisfaction, usability and acceptability of PrEP care modalities; (2) to study associations between socio-demographic, behavioural and psychological characteristics, and PrEP adherence and the study outcomes mentioned under (1).

The EZI-PrEP study is a 2x2 factorial, four-arm, open-label, multi-center, randomized controlled non-inferiority trial. The four arms are: (1) in-clinic 3-monthly monitoring (standard-of-care), (2) in-clinic 6-monthly monitoring, (3) online 3-monthly monitoring, and (4) online 6-monthly monitoring. The primary outcome is defined as a PrEP-less and condom-less anal sex act with a casual partner (i.e., “unprotected act”) as a proxy for HIV infection risk. Eligible are MSM and trans- and gender diverse persons, 18 years or older and eligible for PrEP care at one of the four participating Sexual Health Centers in the Netherlands. The required sample size is 442 participants, and the planned observation time per participant is 24 months. All study participants will get access to a smartphone app, which contains a diary and study questionnaires. Participants are requested to complete the diary on a daily basis during the first 18 months of participation. In addition, those in the online arms will get access to online PrEP care through the app. Participants will complete questionnaires at baseline, 6, 12, 18 and 24 months. Dried blood spots (DBS) for assessment of intracellular tenofovir-diphosphate concentration will be collected at 6 and 12 months. Incidence rates of unprotected acts will be compared between online and in-clinic arms, and between 6-monthly and 3-monthly monitoring arms. Non-inferiority is concluded if the upper limit of the two-sided 97.5% confidence interval of the incidence rate ratio is <1.8.

Results of the main analysis are expected in 2024.

This trial will demonstrate whether online PrEP care and 6-monthly monitoring are non-inferior to standard PrEP care in terms of PrEP adherence. If demonstrated, these modalities may lower barriers of initiating and continuing PrEP use and potentially reduce systemic burden for PrEP providers.

ClinicalTrials.gov, NCT05093036.