All individuals who presented to Trillium with a new confirmed or preliminary HIV diagnosis from October 2018 through September 2021 were screened for this study. Participants were enrolled consecutively, had to be at least 18 years of age, treatment naïve, and presenting for treatment within 21 days of receiving their HIV diagnosis. Confirmatory laboratory results and resistance testing were not required for RSA initiation. Persons who were not eligible for study participation were still offered RSA. Participants underwent baseline assessment and began a single tablet regimen of B/F/TAF on the day of clinic presentation. Trillium’s RSA process includes treatment adherence counseling, health insurance evaluation/navigation, management of social determinants of health, and onsite pharmacy and clinical laboratory services. Follow-up visits were conducted per protocol through 48 weeks at Trillium’s main clinic location in Rochester, NY or via telemedicine.
The primary study endpoints include the proportion of patients who reached HIV-1 viral suppression to < 50 copies/mL within 48 weeks of ART initiation. Real-world treatment advantage was measured in days to clinical milestones, including median days from diagnosis to clinic presentation, from clinic presentation to ART initiation, and diagnosis to ART initiation. Time to virologic suppression was measured as median days from ART initiation to a viral load of < 200 copies/mL and < 50 copies/mL. The viral suppression endpoint of < 200 copies/mL is standard in the literature to represent untransmissible status17, and < 50 copies/mL is the typical clinical standard for virologic suppression18,19.
The secondary endpoints include identification of barriers to initiation and adherence to ART, and participant acceptance of RSA. Participant feedback was collected through a questionnaire developed by the authors and administered at study completion, which asked about perceived barriers to medication initiation, attitudes about starting medication on the day of diagnosis or preliminary diagnosis, and potential interventions to improve the RSA process.
The control group was comprised of all patients of Trillium newly diagnosed with HIV who received standard of care ART initiation between January 2014 and August 2017, prior to RSA implementation at Trillium.
Treatment adherence and retention in care were assessed in the study group only. Treatment adherence was measured as proportion of days covered based on pharmacy dispense data20. Retention in care was measured as the number of patients still on study at 48 weeks.
Statistical Analysis
Statistical analysis was completed using R programming21. All continuous variables were analyzed using Kruskal-Wallis or Wilcox rank test. Fisher exact test was used to analyze categorical variables. A study size of 45 participants was deemed sufficient for a single-center pilot study, based on the number of treatment naïve PLWH who presented to Trillium in the preceding years. The historical control population size was made to be similar to the study size by reviewing how many newly diagnosed patients presented each month prior to RSA initiation at Trillium and selecting the date range that met our population size needs.
Care Team
A multidisciplinary team of providers, care managers, pharmacists, STI testing and prevention specialists, and clinical laboratory services collaborated to create a consistent approach to RSA for all patients. Initial rapid point-of-care HIV testing was performed by Trillium’s STI testing specialists. These testing specialists complete thorough training and annual formal observations to ensure they are proficient at performing point-of-care HIV testing and are prepared to deliver results to patients.
The standard of care at Trillium includes care managers performing a comprehensive needs assessment during a new patient’s first visit to identify and address barriers to care and adherence. Care managers also connect patients with internal and community supportive services to address identified barriers. Internal supportive services available at Trillium include insurance enrollment and navigation, transportation assistance, food pantry access, and medication-assisted treatment (MAT). Community resources include legal aid services, employment services, and domestic violence programs.
An in-house pharmacy at Trillium provides same-day and mail delivered prescription medications. The pharmacists also monitor records of patients taking ART to ensure they have valid prescriptions for refills and have obtained their medications, providing another layer of adherence monitoring and support.
Having a clinical laboratory service which includes a phlebotomy center adjacent to Trillium’s main clinic allows convenient access for patients.
Clinical and Laboratory Evaluations
Participants underwent clinical and laboratory evaluations at the time of enrollment and at subsequent follow-up visits according to the protocol in Appendix A, utilizing commercially available and validated assays. The rapid point-of-care HIV tests used are fourth generation (Determine™ HIV–1/2 Ag/Ab Combo immunoassay, Alere Inc.). The laboratory completes HIV-1 viral load quantification (COBAS 8800 system, Roche Diagnostics) and combined drug resistance and genotyping (GenoSure PRIme assay, Monogram Biosciences).
Study Oversight
The study protocol was reviewed and approved by an external accredited Institutional Review Board (IRB); WCG IRB (Puyallup, WA). Trillium contracted with a site management organization to manage study operations, maintain appropriate documentation, and report adverse events. All participants provided written informed consent and received compensation for their participation in the form of gift cards to local supermarkets.
Screen Failures
Participants had to complete at least one on-treatment visit and blood draw for viral load quantification to be included in statistical analysis. Some participants with false positive reactive tests (reactive rapid point-of-care HIV test with subsequent negative confirmatory testing) were noted. Those with negative confirmatory tests were instructed to stop taking ART and were removed from the study. All efforts were made to retain these patients in care at Trillium and initiate HIV PrEP when appropriate.