Spillover benefit of pre-exposure prophylaxis for HIV prevention: evaluating the importance of effect modification using an agent-based model.

We developed an agent-based model using a trial emulation approach to quantify effect measure modification of spillover effects of pre-exposure prophylaxis (PrEP) for HIV among men who have sex with men (MSM) in the Atlanta-Sandy Springs-Roswell metropolitan area, Georgia. PrEP may impact not only the individual prescribed, but also their partners and beyond, known as spillover. We simulated a two-stage randomised trial with eligible components (≥3 agents with ≥1 HIV+ agent) first randomised to intervention or control (no PrEP). Within intervention components, agents were randomised to PrEP with coverage of 70%, providing insight into a high PrEP coverage strategy. We evaluated effect modification by component-level characteristics and estimated spillover effects on HIV incidence using an extension of randomisation-based estimators. We observed an attenuation of the spillover effect when agents were in components with a higher prevalence of either drug use or bridging potential (if an agent acts as a mediator between ≥2 connected groups of agents). The estimated spillover effects were larger in magnitude among components with either higher HIV prevalence or greater density (number of existing partnerships compared to all possible partnerships). Consideration of effect modification is important when evaluating the spillover of PrEP among MSM.

Brief Report: Use of Pre-Exposure Prophylaxis to Prevent Rapid HIV Transmission Among People Who Inject Drugs in Rural Counties in the United States: A Modeling Study.

BACKGROUND: Despite recent HIV outbreaks among people who inject drugs (PWID) in nonurban US settings, syringe service programs (SSP) are often inaccessible in these communities. Furthermore, pre-exposure prophylaxis (PrEP) awareness and coverage for PWID is limited. We aimed to model the impact of PrEP on HIV transmission among PWID in a rural setting. SETTING: Using a calibrated agent-based model, we simulated HIV transmission in an adult population (n = 14,573 agents) in Scott County, Indiana between 2015 and 2024. METHODS: We modeled PrEP eligibility according to CDC guidelines for PWID. PrEP coverage increased by 15% points in the range 10%-70%. Two counterfactual scenarios were modeled: Unrestricted access for PWID and PrEP for SSP attendees . We calculated the number of new HIV infections and number of person-years on PrEP per averted infection. RESULTS: In the status quo scenario, 153 (95% Simulation Interval: 85, 259) new HIV infections occurred among PWID over 10 years. Compared with the status quo, 40% PrEP coverage resulted in 25% fewer HIV infections in the Unrestricted access for PWID scenario and 10% fewer HIV infections in the PrEP for SSP attendees scenario. The PYPAI was 21 and 43 in the Unrestricted access for PWID and PrEP for SSP attendees scenarios, respectively. CONCLUSION: Our modeling suggests that PrEP provides substantial benefit to PWID in rural US communities, with fewer restrictions on access providing the greatest effect. Control of HIV outbreaks will require expansion of public health interventions that meet the needs of all individuals.

The impact of syringe services program closure on the risk of rebound HIV outbreaks among people who inject drugs: a modeling study.

OBJECTIVE: Despite their effectiveness in preventing the transmission of HIV among people who inject drugs (PWID), syringe services programs (SSPs) in many settings are hampered by social and political opposition. We aimed to estimate the impact of closure and temporary interruption of SSP on the HIV epidemic in a rural United States setting. METHODS: Using an agent-based model (ABM) calibrated to observed surveillance data, we simulated HIV risk behaviors and transmission in adult populations who inject and do not inject drugs in Scott County, Indiana. We projected HIV incidence and prevalence between 2020 and 2025 for scenarios with permanent closure, delayed closure (one additional renewal for 24 months before closure), and temporary closure (lasting 12 months) of an SSP in comparison to persistent SSP operation. RESULTS: With sustained SSP operation, we projected an incidence rate of 0.15 per 100 person-years among the overall population (95% simulation interval: 0.06-0.28). Permanently closing the SSP would cause an average of 58.4% increase in the overall incidence rate during 2021-2025, resulting in a higher prevalence of 60.8% (50.9-70.6%) (18.7% increase) among PWID by 2025. A delayed closure would increase the incidence rate by 38.9%. A temporary closure would cause 12 (35.3%) more infections during 2020-2021. CONCLUSION: Our analysis suggests that temporary interruption and permanent closure of existing SSPs operating in rural United States may lead to 'rebound' HIV outbreaks among PWID. To reach and sustain HIV epidemic control, it will be necessary to maintain existing and implement new SSPs in combination with other prevention interventions.

Comparing Projected Fatal Overdose Outcomes and Costs of Strategies to Expand Community-Based Distribution of Naloxone in Rhode Island.

Importance: In 2021, the state of Rhode Island distributed 10 000 additional naloxone kits compared with the prior year through partnerships with community-based organizations. Objective: To compare various strategies to increase naloxone distribution through community-based programs in Rhode Island to identify one most effective and efficient strategy in preventing opioid overdose deaths (OODs). Design, Setting, and Participants: In this decision analytical model study conducted from January 2016 to December 2022, a spatial microsimulation model with an integrated decision tree was developed and calibrated to compare the outcomes of alternative strategies for distributing 10 000 additional naloxone kits annually among all individuals at risk for opioid overdose in Rhode Island. Interventions: Distribution of 10 000 additional naloxone kits annually, focusing on people who inject drugs, people who use illicit opioids and stimulants, individuals at various levels of risk for opioid overdose, or people who misuse prescription opioids vs no additional kits (status quo). Two expanded distribution implementation approaches were considered: one consistent with the current spatial distribution patterns for each distribution program type (supply-based approach) and one consistent with the current spatial distribution of individuals in each of the risk groups, assuming that programs could direct the additional kits to new geographic areas if required (demand-based approach). Main Outcomes and Measures: Witnessed OODs, cost per OOD averted (efficiency), geospatial health inequality measured by the Theil index, and between-group variance for OOD rates. Results: A total of 63 131 simulated individuals were estimated to be at risk for opioid overdose in Rhode Island based on current population data. With the supply-based approach, prioritizing additional naloxone kits to people who use illicit drugs averted more witnessed OODs by an estimated mean of 18.9% (95% simulation interval [SI], 13.1%-30.7%) annually. Expanded naloxone distribution using the demand-based approach and focusing on people who inject drugs had the best outcomes across all scenarios, averting an estimated mean of 25.3% (95% SI, 13.1%-37.6%) of witnessed OODs annually, at the lowest mean incremental cost of $27 312 per OOD averted. Other strategies were associated with fewer OODs averted at higher costs but showed similar patterns of improved outcomes and lower unit costs if kits could be reallocated to areas with greater need. The demand-based approach reduced geospatial inequality in OOD rates in all scenarios compared with the supply-based approach and status quo. Conclusions and Relevance: In this decision analytical model study, variations in the effectiveness, efficiency, and health inequality of the different naloxone distribution expansion strategies and approaches were identified. Future efforts should be prioritized for people at highest risk for overdose (those who inject drugs or use illicit drugs) and redirected toward areas with the greatest need. These findings may inform future naloxone distribution priority settings.