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Additional file 1: Appendix A.

Background: To maximize public health impact and cost-effectiveness, HIV pre-exposure prophylaxis (PrEP) must reach individuals at high HIV risk. Referrals for PrEP can be self- or provider-initiated, but there are several challenges to both. We assessed whether HIV risk differed by referral source among gay, bisexual and other men who have sex (gbMSM) screening for an HIV PrEP demonstration project. Methods: PREPARATORY-5 was an open-label PrEP demonstration project enrolling gbMSM at high risk of HIV acquisition in Toronto, Canada. Study eligibility criteria related to high risk was defined as scoring ≥10 on the HIV Incidence Risk Index for MSM (HIRI-MSM) and engaging in at least 1 act of condomless receptive anal sex within the past 6 months. Recruitment was promoted through self-referrals (ads in a sexual networking app and gay newspaper/website) and provider-referrals (10 community-based organizations, CBOs). HIV risk score (HIRI-MSM) and syndemic health burden were measured among gbMSM screened for study participation and compared according to referral source. Results: Between October 16 and December 30, 2014, online ads generated 1518 click-throughs and CBOs referred 115 individuals. Overall, 165 men inquired about the trial, of which 86 underwent screening. The majority of screened men were self-referrals (60.5%), scored ≥10 on HIRI-MSM (96.5%), and reported condomless receptive anal sex in the past 6 months (74.2%). Self- and provider-referrals had similarly high HIV risk profiles, with a median (IQR) HIRI-MSM score of 26.0 (19.0–32.5) and 28.5 (20.0–34.0) (p = 0.3), and 75.0% and 73.5% reporting condomless receptive anal sex (p = 0.9), respectively. The overall burden of syndemic health problems was also high, with approximately one-third overall identified as having depressive symptoms (39.5%), alcohol-related problems (39.5%), multiple drug use (31.4%), or sexual compulsivity (31.4%). There were no significant differences in syndemic health problems by referral source. Conclusions: HIV risk and syndemic burden were high among gbMSM presenting for this PrEP demonstration project regardless of referral source. Self-referral may be a useful and efficient strategy for identifying individuals suitable for PrEP use. Online strategies and CBOs working in gay men’s health may play important roles in connecting individuals at high HIV risk to PrEP services. Trial registration ClinicalTrials.gov NCT02149888 . Registered May 12th 2014.

Background: Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case. Methods: This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation. Participants will be individuals aged > 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35, and 90 includes comprehensive epidemiological, clinical, microbiologic, and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power at α = 0.05, assuming the secondary attack rate in ring members (p0) = 15%, 5 contacts per case and intra-class correlation coefficient (ICC) = 0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates of p0, ICC, and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Participants who test positive at baseline will be excluded from the primary analysis but will be maintained for additional analyses to examine the impact of LPV/r on early treatment. Discussion: Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection. Trial registration This trial was registered at www.ClinicalTrials.gov ( NCT04321174 ) on March 25, 2020.