Disseminated Effects in Agent-Based Models: A Potential Outcomes Framework and Application to Inform Preexposure Prophylaxis Coverage Levels for HIV Prevention.

Preexposure prophylaxis (PrEP) for prevention of human immunodeficiency virus (HIV) infection may benefit not only the person who uses it but also their uninfected sexual risk contacts. We developed an agent-based model using a novel trial emulation approach to quantify disseminated effects of PrEP use among men who have sex with men in Atlanta, Georgia, from 2015 to 2017. Model components (subsets of agents connected through partnerships in a sexual network but not sharing partnerships with any other agents) were first randomized to an intervention coverage level or the control group; then, within intervention components, eligible agents were randomized to receive or not receive PrEP. We calculated direct and disseminated (indirect) effects using randomization-based estimators and report corresponding 95% simulation intervals across scenarios ranging from 10% coverage in the intervention components to 90% coverage. A population of 11,245 agents was simulated, with an average of 1,551 components identified. When comparing agents randomized to no PrEP in 70% coverage components with control agents, there was a 15% disseminated risk reduction in HIV incidence (risk ratio = 0.85, 95% simulation interval: 0.65, 1.05). Persons not on PrEP may receive a protective benefit by being in a sexual network with higher PrEP coverage. Agent-based models are useful for evaluating possible direct and disseminated effects of HIV prevention modalities in sexual networks.

Implementation of Syringe Services Programs to Prevent Rapid Human Immunodeficiency Virus Transmission in Rural Counties in the United States: A Modeling Study.

BACKGROUND: Syringe services programs (SSPs) are effective venues for delivering harm-reduction services to people who inject drugs (PWID). However, SSPs often face significant barriers to implementation, particularly in the absence of known human immunodeficiency virus (HIV) outbreaks. METHODS: Using an agent-based model, we simulated HIV transmission in Scott County, Indiana, a rural county with a 1.7% prevalence of injection drug use. We compared outcomes arising in the absence of an SSP, in the presence of a pre-existing SSP, and with implementation of an SSP after the detection of an HIV outbreak among PWID over 5 years following the introduction of a single infection into the network. RESULTS: In the absence of an SSP, the model predicted an average of 176 infections among PWID over 5 years or an incidence rate of 12.1/100 person-years. Proactive implementation averted 154 infections and decreased incidence by 90.3%. With reactive implementation beginning operations 10 months after the first infection, an SSP would prevent 107 infections and decrease incidence by 60.8%. Reductions in incidence were also observed among people who did not inject drugs. CONCLUSIONS: Based on model predictions, proactive implementation of an SSP in Scott County had the potential to avert more HIV infections than reactive implementation after the detection of an outbreak. The predicted impact of reactive SSP implementation was highly dependent on timely implementation after detecting the earliest infections. Consequently, there is a need for expanded proactive SSP implementation in the context of enhanced monitoring of outbreak vulnerability in Scott County and similar rural contexts.

Potential drivers of HIV acquisition in African-American women related to mass incarceration: an agent-based modelling study.

BACKGROUND: The United States has the highest incarceration rate in the world. Incarceration can increase HIV risk behaviors for individuals involved with the criminal justice system and may be a driver of HIV acquisition within the community. METHODS: We used an agent-based model to simulate HIV transmission in a sexual-contact network representing heterosexual African American men and women in Philadelphia to identify factors influencing the impact of male mass incarceration on HIV acquisition in women. The model was calibrated using surveillance data and assumed incarceration increased the number of sexual contacts and decreased HIV care engagement for men post-release. Incarceration of a partner increased the number of sexual contacts for women. We compared a counterfactual scenario with no incarceration to scenarios varying key parameters to determine what factors drove HIV acquisition in women. RESULTS: Setting the duration of male high-risk sexual behavior to two years post-release increased the number of HIV transmissions to women by more than 20%. Decreasing post-release HIV care engagement and increasing HIV acquisition risk attributable to sexually transmitted infections (STIs) also increased the number of HIV transmissions to women. Changing the duration of risk behavior for women, the proportion of women engaging in higher risk behavior, and the relative risk of incarceration for HIV-infected men had minimal impact. CONCLUSION: The mass incarceration of African American men can increase HIV acquisition in African American women on a population-level through factors including post-release high-risk behaviors, disruption of HIV care engagement among formerly incarcerated men, and increased STI prevalence. These findings suggest that the most influential points of intervention may be programs seeking to reduce male risk behaviors and promote HIV care engagement post-release, as well as STI testing and treatment programs for recently incarcerated men, as well as women with incarcerated partners.

Clinical care of incarcerated people with HIV, viral hepatitis, or tuberculosis.

The burden of HIV/AIDS and other transmissible diseases is higher in prison and jail settings than in the non-incarcerated communities that surround them. In this comprehensive review, we discuss available literature on the topic of clinical management of people infected with HIV, hepatitis B and C viruses, and tuberculosis in incarcerated settings in addition to co-occurrence of one or more of these infections. Methods such as screening practices and provision of treatment during detainment periods are reviewed to identify the effect of community-based treatment when returning inmates into the general population. Where data are available, we describe differences in the provision of medical care in the prison and jail settings of low-income and middle-income countries compared with high-income countries. Structural barriers impede the optimal delivery of clinical care for prisoners, and substance use, mental illness, and infectious disease further complicate the delivery of care. For prison health care to reach the standards of community-based health care, political will and financial investment are required from governmental, medical, and humanitarian organisations worldwide. In this review, we highlight challenges, gaps in knowledge, and priorities for future research to improve health-care in institutions for prisoners.

The risk of HIV transmission at each step of the HIV care continuum among people who inject drugs: a modeling study.

BACKGROUND: People who inject drugs (PWID) are at continued risk for HIV in the U.S., and experience disparities across the HIV care continuum compared to other high-risk groups. Estimates of the risk of HIV transmission at each stage of the care continuum may assist in identifying public health priorities for averting incident infections among PWID, in addition to transmissions to sexual partners of PWID. METHODS: We created an agent-based model simulating HIV transmission and the HIV care continuum for PWID in New York City (NYC) in 2012. To account for sexual transmission arising from PWID to non-PWID, the simulation included the entire adult NYC population. Using surveillance data and estimates from the National HIV Behavioral Surveillance system, we simulated a dynamic sexual and injecting network. We estimated the proportion of HIV transmission events attributable to PWID in the following categories, those: without an HIV diagnosis ('Undiagnosed'); diagnosed but not on antiretroviral therapy (ART) ('Diagnosed - not on ART'); those who initiated ART but were not virally suppressed ('Unsuppressed'); and, those who achieved viral suppression ('Suppressed'). RESULTS: We estimated HIV incidence among PWID to be 113 per 100,000 person-years in 2012, with an overall incidence rate for the entire adult NYC population of 33 per 100,000 person-years. Despite accounting for only 33% of the HIV-infected PWID population, the Undiagnosed were associated with 52.6% (95% simulation interval [95% SI]: 47.1-57.0%) of total transmission events. The Diagnosed - not on ART population contributed the second-largest proportion of HIV transmissions, with 36.6% (95% SI: 32.2-41.5%). The Unsuppressed population contributed 8.7% (95% SI: 5.6-11.8%), and Suppressed 2.1% (95% SI: 1.1-3.9%), relatively little of overall transmission. CONCLUSIONS: Among PWID in NYC, more than half (53%) of transmissions were from those who were unaware of their infection status and more than 36% were due to PWID who knew their status, but were not on treatment. Our results indicate the importance of early diagnosis and interventions to engage diagnosed PWID on treatment to further suppress population-level HIV transmission. Future HIV prevention research should focus on the elimination of identified and potential barriers to the testing, diagnosis, and retention of PWID on HIV treatment.

Potential Impact of Targeted HIV Pre-Exposure Prophylaxis Uptake Among Male Sex Workers.

Little is known about the potential population-level impact of HIV pre-exposure prophylaxis (PrEP) use among cisgender male sex workers (MSWs), a high-risk subset of cisgender men who have sex with men (MSM). Using an agent-based model, we simulated HIV transmission among cisgender MSM in Rhode Island to determine the impacts of PrEP implementation where cisgender MSWs were equally ("standard expansion") or five times as likely ("focused expansion") to initiate PrEP compared to other cisgender MSM. Without PrEP, the model predicted 920 new HIV infections over a decade, or an average incidence of 0.39 per 100 person-years. In a focused expansion scenario where 15% of at-risk cisgender MSM used PrEP, the total number of new HIV infections was reduced by 58.1% at a cost of $57,180 per quality-adjusted life-year (QALY) gained. Focused expansion of PrEP use among cisgender MSWs may be an efficient and cost-effective strategy for reducing HIV incidence in the broader population of cisgender MSM.

Correction: Improving the impact of HIV pre-exposure prophylaxis implementation in small urban centers among men who have sex with men: An agent-based modelling study.

[This corrects the article DOI: 10.1371/journal.pone.0199915.].

Cost-Effectiveness of a Statewide Pre-Exposure Prophylaxis Program for Gay, Bisexual, and Other Men Who Have Sex with Men.

Pre-exposure prophylaxis (PrEP) is an effective tool for preventing HIV infection among men who have sex with men (MSM), but its cost-effectiveness has varied across settings. Using an agent-based model, we projected the cost-effectiveness of a statewide PrEP program for MSM in Rhode Island over the next decade. In the absence of PrEP, the model predicted an average of 830 new HIV infections over ten years. Scaling up the existing PrEP program to cover 15% of MSM with ten or more partners each year could reduce the number of new HIV infections by 33.1% at a cost of $184,234 per quality-adjusted life-year (QALY) gained. Expanded PrEP use among MSM at high risk for HIV infection has the potential to prevent a large number of new HIV infections but the high drug-related costs may limit the cost-effectiveness of this intervention.

Decreasing HIV transmissions to African American women through interventions for men living with HIV post-incarceration: An agent-based modeling study.

BACKGROUND: Incarceration and HIV disproportionately impact African American communities. The mass incarceration of African American men is hypothesized to increase HIV acquisition risk for African American women. Interventions optimizing HIV care engagement and minimizing sexual risk behaviors for men living with HIV post-incarceration may decrease HIV incidence. METHODS: Using an agent-based model, we simulated a sexual and injection drug using network representing the African American population of Philadelphia. We compared intervention strategies for men living with HIV post-incarceration by the number of averted HIV transmissions to women within the community. Three interventions were evaluated: a 90-90-90 scenario scaling up HIV testing, ART provision, and ART adherence; a behavioral intervention decreasing sexual risk behaviors; and a combination intervention involving both. RESULTS: The status quo scenario projected 2,836 HIV transmissions to women over twenty years. HIV transmissions to women decreased by 29% with the 90-90-90 intervention, 23% with the behavioral intervention, and 37% with both. The number of men living with HIV receiving the intervention needed in order to prevent a single HIV transmission ranged between 6 and 10. CONCLUSION: Interventions to improve care engagement and decrease sexual risk behaviors post-incarceration for men living with HIV have the potential to decrease HIV incidence within African American heterosexual networks.

Improving the impact of HIV pre-exposure prophylaxis implementation in small urban centers among men who have sex with men: An agent-based modelling study.

OBJECTIVES: Identifying prescribing strategies that improve the efficiency of PrEP should increase its impact at the population level. This study identifies PrEP allocation criteria that most effectively reduce 10-year HIV incidence by 25%, in accordance with the US National HIV/AIDS Strategy's goal for the proportionate reduction in new diagnoses. METHODS: We used a discrete-time stochastic agent-based model to simulate several PrEP engagement strategies. The model represented MSM aged 15-74 in Rhode Island and was calibrated to statewide prevalence from 2009-2014. We simulated HIV transmission in the absence of PrEP and compared the following PrEP engagement scenarios: 1) allocation to the current patient population; 2) random allocation; 3) allocation to MSM with greater than 5 sexual partners in one year; 4) allocation to MSM with greater than 10 sexual partners in one year. For each scenario and coverage level we estimated the number and proportion of infections averted and the person-years on PrEP per averted infection. RESULTS: In 2014, HIV prevalence before PrEP implementation was between 4% and 5%. In the No PrEP scenario 826 new infections (95% simulation limits [SL]: 711, 955) occurred over 10 years, with an incidence rate of 3.51 per 1000 person-years (95% SL: 3.00, 4.08). Prevalence rose to 7.4% (95% SL: 6.7, 8.1). None of the PrEP scenarios reduced new HIV infections by 25% while covering less than 15% of the HIV-uninfected population. At 15% coverage, allocating PrEP to the current patient population, MSM with greater than 5 sexual partners in a year, and MSM with greater than 10 partners reduced new infections by at least 25%, requiring 161 (95% SL: 115, 289), 150 (95% SL: 107, 252), and 128 (95% SL: 100, 184) person-years on PrEP per averted infection, respectively. CONCLUSIONS: Engaging MSM with high numbers of sexual partners would improve the population-level impact and efficiency of PrEP in settings where PrEP coverage remains low. However, the sustained population-level PrEP coverage needed to reduce new infections by 25% is substantially higher than current levels of PrEP uptake.

Potential effectiveness of long-acting injectable pre-exposure prophylaxis for HIV prevention in men who have sex with men: a modelling study.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) prevents HIV infection in men who have sex with men (MSM); however, adherence is an ongoing concern. Long-acting injectable PrEP is being tested in phase 3 trials and could address challenges associated with adherence. We examined the potential effectiveness of long-acting injectable PrEP compared with oral PrEP in MSM. METHODS: We used an agent-based model to simulate HIV transmission in a dynamic network of 11 245 MSM in Atlanta, GA, USA. We used raw data from studies in macaque models and pharmacokinetic data from safety trials to estimate the time-varying efficacy of long-acting injectable PrEP. The effect of long-acting injectable PrEP on the cumulative number of new HIV infections over 10 years (2015-24) was compared with no PrEP and daily oral PrEP across a range of coverage levels. Sensitivity analyses were done with varying maximum efficacy and drug half-life values. FINDINGS: In the absence of PrEP, the model predicted 2374 new HIV infections (95% simulation interval [SI] 2345-2412) between 2015 and 2024. The cumulative number of new HIV infections was reduced in all scenarios in which MSM received long-acting injectable PrEP compared with oral PrEP. At a coverage level of 35%, compared with no PrEP, long-acting injectable PrEP led to a 44% reduction in new HIV infections (1044 new infections averted [95% SI 1018-1077]) versus 33% (792 infections averted [763-821]) for oral PrEP. The relative benefit of long-acting injectable PrEP was sensitive to the assumed efficacy of injections received every 8 weeks, discontinuation rates, and terminal drug half-life. INTERPRETATION: Long-acting injectable PrEP has the potential to produce larger reductions in HIV transmission in MSM than oral PrEP. However, the real-world, population-level impact of this approach will depend on uptake of this prevention method and its effectiveness, as well as retention of patients in clinical care. FUNDING: National Institute on Drug Abuse and National Institute of Mental Health.

Effect of Racial Inequities in Pre-exposure Prophylaxis Use on Racial Disparities in HIV Incidence Among Men Who Have Sex With Men: A Modeling Study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) uptake has been slow among African American men who have sex with men (AAMSM) in the United States. We used an agent-based model (ABM) to simulate race-specific PrEP coverage to estimate their impact on racial disparities in HIV incidence among MSM in Atlanta, GA. METHODS: An ABM was constructed to simulate HIV transmission in a dynamic network of 10,000 MSM over 10 years, beginning in 2015. We modeled a base scenario with estimated PrEP coverage of 2.5% among AAMSM and 5.0% among white MSM (WMSM). We then compared HIV incidence over 10 years and calculated a disparity ratio of AAMSM to WMSM incidence rates across varying PrEP scale-up scenarios, with equal and unequal coverage among AAMSM and WMSM. RESULTS: Assuming current coverage remains constant, the model predicts HIV incidence rates of 2.95 and 1.76 per 100 person-years among AAMSM and WMSM, respectively, with a disparity ratio of 1.68. If PrEP coverage was to increase 6-fold without addressing inequities in PrEP uptake, the model predicts incidences of 2.65 and 1.34, corresponding to a mean decrease of 10.4% and 24.0% in HIV incidence, respectively. This stronger benefit for WMSM increased the disparity ratio to 1.98. Equal PrEP coverage among AAMSM and WMSM resulted in lower incidence rates overall with lower disparity ratios. CONCLUSIONS: Lower uptake among AAMSM relative to WMSM may limit the population-level impact of PrEP use among AAMSM, which may ultimately culminate in wider racial disparities in HIV incidence among MSM.

Acute HIV infection transmission among people who inject drugs in a mature epidemic setting.

OBJECTIVE: Estimates for the contribution of transmission arising from acute HIV infections (AHIs) to overall HIV incidence vary significantly. Furthermore, little is known about AHI-attributable transmission among people who inject drugs (PWID), including the extent to which interventions targeting chronic infections (e.g. HAART as prevention) are limited by AHI transmission. Thus, we estimated the proportion of transmission events attributable to AHI within the mature HIV epidemic among PWID in New York City (NYC). DESIGN: Modeling study. METHODS: We constructed an interactive sexual and injecting transmission network using an agent-based model simulating the HIV epidemic in NYC between 1996 and 2012. Using stochastic microsimulations, we cataloged transmission from PWID based on the disease stage of index agents to determine the proportion of infections transmitted during AHI (in primary analyses, assumed to last 3 months). RESULTS: Our calibrated model approximated the epidemiological features of the mature HIV epidemic in NYC between 1996 and 2012. Annual HIV incidence among PWID dropped from approximately 1.8% in 1996 to 0.7% in 2012. Over the 16-year period, AHI accounted for 4.9% (10th/90th percentile: 0.1-12.3%) of incident HIV cases among PWID. The annualized contribution of AHI increased over this period from 3.6% in 1996 to 5.9% in 2012. CONCLUSION: Our results suggest that, in mature epidemics such as NYC, between 3% and 6% of transmission events are attributable to AHI among PWID. Current HIV treatment as prevention strategies are unlikely to be substantially affected by AHI-attributable transmission among PWID populations in mature epidemic settings.