Publications by authors named "Natasha K Martin"

95 Publications

Identifying counties at risk of high overdose mortality burden during the emerging fentanyl epidemic in the USA: a predictive statistical modelling study.

Lancet Public Health 2021 Jun 9. Epub 2021 Jun 9.

Department of Medicine, University of California, San Diego, CA, USA.

Background: The emergence of fentanyl around 2013 represented a new, deadly stage of the opioid epidemic in the USA. We aimed to develop a statistical regression approach to identify counties at the highest risk of high overdose mortality in the subsequent years by predicting annual county-level overdose death rates across the contiguous USA and to validate our approach against observed overdose mortality data collected between 2013 and 2018.

Methods: We fit mixed-effects negative binomial regression models to predict overdose death rates in the subsequent year for 2013-18 for all contiguous state counties in the USA (ie, excluding Alaska and Hawaii). We used publicly available county-level data related to health-care access, drug markets, socio-demographics, and the geographical spread of opioid overdose as model predictors. The crude number of county-level overdose deaths was extracted from restricted US Centers for Disease Control and Prevention mortality records. To predict county-level overdose rates for the year 201X: (1) a model was trained on county-level predictor data for the years 2010-201(X-2) paired with county-level overdose deaths for the year 2011-201(X-1); (2) county-level predictor data for the year 201(X-1) was fed into the model to predict the 201X county-level crude number of overdose deaths; and (3) the latter were converted to a population-adjusted rate. For comparison, we generated a benchmark set of predictions by applying the observed slope of change in overdose death rates in the previous year to 201(X-1) rates. To assess the predictive performance of the model, we compared predicted values (of both the model and benchmark) to observed values by (1) calculating the mean average error, root mean squared error, and Spearman's correlation coefficient and (2) assessing the proportion of counties in the top decile (10%) of overdose death rates that were correctly predicted as such. Finally, in a post-hoc analysis, we sought to identify variables with greatest predictive utility.

Findings: Between 2013 and 2018, among the 3106 US counties included, our modelling approach outperformed the benchmark strategy across all metrics. The observed average county-level overdose death rate rose from 11·8 per 100 000 people in 2013 to 15·4 in 2017 before falling to 14·6 in 2018. Our negative binomal modelling approach similarly identified an increasing trend, predicting an average 11·8 deaths per 100 000 in 2013, up to 15·1 in 2017, and increasing further to 16·4 in 2018. The benchmark model over-predicted average death rates each year, ranging from 13·0 per 100 000 in 2013 to 18·3 in 2018. Our modelling approach successfully ranked counties by overdose death rate identifying between 42% and 57% of counties in the top decile of overdose mortality (compared with 29% and 43% using the benchmark) each year and identified 194 of the 808 counties with emergent overdose outbreaks (ie, newly entered the top decile) across the study period, versus 31 using the benchmark. In the post-hoc analysis, we identified geospatial proximity of overdose in nearby counties, opioid prescription rate, presence of an urgent care facility, and several economic indicators as the variables with the greatest predictive utility.

Interpretation: Our model shows that a regression approach can effectively predict county-level overdose death rates and serve as a risk assessment tool to identify future high mortality counties throughout an emerging drug use epidemic.

Funding: National Institute on Drug Abuse.
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http://dx.doi.org/10.1016/S2468-2667(21)00080-3DOI Listing
June 2021

The estimated hepatitis C seroprevalence and key population sizes in San Diego in 2018.

PLoS One 2021 9;16(6):e0251635. Epub 2021 Jun 9.

Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, CA, United States of America.

Background: The Eliminate Hepatitis C San Diego County Initiative was established to provide a roadmap to reduce new HCV infections by 80% and HCV-related deaths by 65% by 2030. An estimate of the burden of HCV infections in San Diego County is necessary to inform planning and evaluation efforts. Our analysis was designed to estimate the HCV burden in San Diego County in 2018.

Methods: We synthesized data from the American Community Survey, Centers for Disease Control and Prevention, California Department of Public Health, Public Health Branch of California Correctional Health Care Services, San Diego Blood Bank, and published literature. Burden estimates were stratified by subgroup (people who inject drugs in the community [PWID], men who have sex with men in the community [MSM], general population in the community [stratified by age and sex], and incarcerated individuals). To account for parameter uncertainty, 100,000 parameter sets were sampled from each parameter's uncertainty distribution, and used to calculate the mean and 95% confidence interval estimates of the number of HCV seropositive adults in San Diego in 2018.

Findings: We found there were 55,354 (95% CI: 25,411-93,329) adults with a history of HCV infection in San Diego County in 2018, corresponding to an HCV seroprevalence of 2.1% (95% CI: 1.1-3.4%). Over 40% of HCV infections were among the general population aged 55-74 and one-third were among PWID.

Conclusion: Our study found that the largest share of infections was among adults aged 55-74, indicating the importance of surveillance, prevention, testing, and linkages to care in this group to reduce mortality. Further, programs prioritizing PWID for increased HCV testing and linkage to care are important for reducing new HCV infections.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251635PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189442PMC
June 2021

Evaluating the prevention benefit of HCV treatment: Modelling the SToP-C treatment as prevention study in prisons.

Hepatology 2021 Jun 9. Epub 2021 Jun 9.

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Background & Aims: Between 2014-2019, the SToP-C trial observed a halving in HCV incidence in four Australian prisons following scale-up of direct-acting antiviral (DAA) therapy. However, the contribution of HCV treatment to this decline is unclear due to the study not having a control group. We used modelling to consider this question.

Approach & Results: We parameterised and calibrated a dynamic model of HCV transmission in prisons to data from each SToP-C prison on incarceration dynamics, injecting drug use, HCV prevalence trends among prison entrants, baseline HCV incidence before treatment scale-up, and subsequent HCV treatment scale-up. The model projected the decrease in HCV incidence resulting from increases in HCV treatment and other effects. We assessed whether the model agreed better with observed reductions in HCV incidence overall and by prison if we included HCV treatment scale-up, and its prevention benefits, or did not. The model estimated how much of the observed decrease in HCV incidence was due to HCV treatment in prison. The model projected a decrease in HCV incidence of 48.5% (95% uncertainty interval [UI] 41.9-54.1%) following treatment scale-up across the four prisons, agreeing with the observed HCV incidence decrease (47.6%, 95% confidence interval 23.4-64.2%) from the SToP-C trial. Without any in-prison HCV treatment, the model indicated that incidence would have decreased by 7.2% (95%UI -0.3-13.6%). This suggests 85.1% (95%UI 72.6-100.6%) of the observed halving in incidence was from HCV treatment scale-up, with the remainder from observed decreases in HCV prevalence among prison entrants (14.9%; 95%UI -0.6-27.4%).

Conclusions: Our results demonstrate the prevention benefits of scaling up HCV treatment in prison settings. Prison-based DAA scale-up should be an important component of HCV elimination strategies.
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http://dx.doi.org/10.1002/hep.32002DOI Listing
June 2021

Evaluation of hepatitis C treatment-as-prevention within Australian prisons (SToP-C): a prospective cohort study.

Lancet Gastroenterol Hepatol 2021 Jul 7;6(7):533-546. Epub 2021 May 7.

The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia. Electronic address:

Background: Limited empirical evidence exists for the effectiveness of hepatitis C virus (HCV) treatment-as-prevention. The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study aimed to assess the effect of HCV treatment-as-prevention in the prison setting.

Methods: SToP-C was a prospective study, including a before-and-after analysis, within a cohort of people incarcerated in two maximum-security prisons (male) and two medium-security prisons (one male, one female) in New South Wales, Australia. All prison inmates aged at least 18 years were eligible for enrolment. After HCV testing, participants were monitored for risk behaviours and HCV infection, among three sub-populations: uninfected (HCV antibody-negative); previously infected (HCV antibody-positive, HCV RNA-negative); and infected (HCV antibody and HCV RNA-positive). Uninfected participants were followed up every 3-6 months to detect HCV primary infection and previously infected participants were followed up every 3-6 months to detect re-infection. Participants with HCV infection were assessed for treatment, initially standard-of-care treatment (administered by prison health services) from 2014 to mid-2017, then direct-acting antiviral (DAA) treatment scale-up from mid-2017 onwards (12 weeks of sofosbuvir plus velpatasvir, administered through SToP-C). Participants were followed up until study closure in November, 2019. The primary study outcome was HCV incidence before and after DAA treatment scale-up among participants at risk of HCV primary infection or re-infection. This study is registered with ClinicalTrials.gov, NCT02064049.

Findings: Between Oct 30, 2014, and Sept 30, 2019, 3691 participants were enrolled in the SToP-C study. 719 (19%) participants had detectable HCV RNA, 2240 (61%) were at risk of primary HCV infection, and 725 (20%) were at risk of re-infection at baseline. DAA treatment was initiated in 349 (70%) of 499 eligible participants during the treatment scale-up period. The HCV incidence analysis comprised 1643 participants at risk of HCV infection or re-infection during longitudinal follow-up (median age 33 years [IQR 27-42]; 1350 [82%] male). 487 (30%) of 1643 participants reported injecting drugs in prison. HCV incidence decreased from 8·31 per 100 person-years in the pre-treatment scale-up period to 4·35 per 100 person-years in the post-treatment scale-up period (incidence rate ratio [IRR] 0·52 [95% CI 0·36-0·78]; p=0·0007). The incidence of primary infection decreased from 6·64 per 100 person-years in the pre-treatment scale-up period to 2·85 per 100 person-years in the post-treatment scale-up period (IRR 0·43 [95% CI 0·25-0·74]; p=0·0019), whereas the incidence of re-infection decreased from 12·36 per 100 person-years to 7·27 per 100 person-years (0·59 [0·35-1·00]; p=0·050). Among participants reporting injecting drugs during their current imprisonment, the incidence of primary infection decreased from 39·08 per 100 person-years in the pre-treatment scale-up period to 14·03 per 100 person-years in the post-treatment scale-up period (IRR 0·36 [95% CI 0·16-0·80]; p=0·0091), and the incidence of re-infection decreased from 15·26 per 100 person-years to 9·34 per 100 person-years (0·61 [0·34-1·09]; p=0·093). The adjusted analysis (adjusted for age, Indigenous Australian ethnicity, duration of stay in prison, previous imprisonment, injecting drug use status, and prison site) indicated a significant reduction in the risk of HCV infection between the pre-DAA treatment scale-up and post-DAA treatment scale-up periods (adjusted hazard ratio 0·50 [95% CI 0·33-0·76]; p=0·0014).

Interpretation: DAA treatment scale-up was associated with reduced HCV incidence in prison, indicative of a beneficial effect of HCV treatment-as-prevention in this setting. These findings support broad DAA treatment scale-up within incarcerated populations.

Funding: Australian National Health and Medical Research Council Partnership Project Grant and Gilead Sciences.
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http://dx.doi.org/10.1016/S2468-1253(21)00077-7DOI Listing
July 2021

Discussion of article by Ellenberg and Morris.

Stat Med 2021 May;40(11):2511-2512

Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California, USA.

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http://dx.doi.org/10.1002/sim.8945DOI Listing
May 2021

The cost-effectiveness of case-finding strategies for achieving hepatitis C elimination among men who have sex with men in the UK.

J Viral Hepat 2021 Jun 1;28(6):897-908. Epub 2021 Apr 1.

Population Health Sciences, University of Bristol, Bristol, UK.

Modelling suggests hepatitis C virus (HCV) elimination is possible among men who have sex with men (MSM), with key screening groups including HIV-diagnosed MSM and MSM using pre-exposure prophylaxis (PrEP). Mathematical modelling was used to determine the cost-effectiveness of HCV case-finding strategies among MSM from the provider perspective, and to determine which interventions could achieve a 90% reduction in HCV incidence over 2015-2030. At baseline, we assumed symptomatic screening in HIV-negative MSM (including PrEP users) and 12-monthly screening among HIV-diagnosed MSM. Improved case-finding strategies included screening alongside HIV testing in HIV-negative MSM not using PrEP (PrEP non-users); 12/6/3-monthly screening in PrEP users; and 6-monthly screening in HIV-diagnosed MSM, with the cost-effectiveness being compared incrementally. Costs (GBP) and quality-adjusted life years (QALYs) were assessed to estimate the mean incremental cost-effectiveness ratio (ICER) with a time horizon to 2050, compared to a willingness-to-pay threshold of £20,000/QALY. From the baseline, the most incrementally cost-effective strategy is to firstly undertake: (1) 12-monthly HCV screening of PrEP users (gaining 6715 QALYs with ICER £1760/QALY), followed by (2) HCV screening among PrEP non-users alongside HIV testing (gaining 7048 QALYs with ICER £4972/QALY). Compared to the baseline, this combined strategy would cost £46.9 (95%CrI £25.3-£66.9) million and achieve the HCV elimination target in 100% of model runs. Additional screening incurs ICERs >£20,000/QALY compared to this combined strategy. In conclusion, HCV elimination can be achieved cost-effectively among UK MSM. Policymakers should consider scaling-up HCV screening in HIV-negative MSM, especially PrEP users, for achieving this target.
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http://dx.doi.org/10.1111/jvh.13503DOI Listing
June 2021

Cost and cost-effectiveness of a real-world HCV treatment program among HIV-infected individuals in Myanmar.

BMJ Glob Health 2021 Feb;6(2)

Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California, USA.

Introduction: Over half of those hepatitis C virus (HCV)/HIV coinfected live in low-income and middle-income countries, and many remain undiagnosed or untreated. In 2016, Médecins Sans Frontières (MSF) established a direct-acting antiviral (DAA) treatment programme for people HCV/HIV coinfected in Myanmar. The purpose of our study was to evaluate the real-world cost and cost-effectiveness of this programme, and potential cost-effectiveness if implemented by the Ministry of Health (MoH).

Methods: Costs (patient-level microcosting) and treatment outcomes were collected from the MSF prospective cohort study in Dawei, Myanmar. A Markov model was used to assess cost-effectiveness of the programme compared with no HCV treatment from a health provider perspective. Estimated lifetime and healthcare costs (in 2017 US$) and health outcomes (in disability-adjusted life-years (DALYs)) were simulated to calculate the incremental cost-effectiveness ratio (ICER), compared with a willingness-to-pay threshold of per capita Gross Domestic Product in Myanmar ($1250). We evaluated cost-effectiveness with updated quality-assured generic DAA prices and potential cost-effectiveness of a proposed simplified treatment protocol with updated DAA prices if implemented by the MoH.

Results: From November 2016 to October 2017, 122 with HIV/HCV-coinfected patients were treated with DAAs (46% with cirrhosis), 96% (n=117) achieved sustained virological response. Mean treatment costs were $1229 (without cirrhosis) and $1971 (with cirrhosis), with DAA drugs being the largest contributor to cost. Compared with no treatment, the program was cost-effective (ICER $634/DALY averted); more so with updated prices for quality-assured generic DAAs (ICER $488/DALY averted). A simplified treatment protocol delivered by the MoH could be cost-effective if associated with similar outcomes (ICER $316/DALY averted).

Conclusions: Using MSF programme data, the DAA treatment programme for HCV among HIV-coinfected individuals is cost-effective in Myanmar, and even more so with updated DAA prices. A simplified treatment protocol could enhance cost-effectiveness if further rollout demonstrates it is not associated with worse treatment outcomes.
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http://dx.doi.org/10.1136/bmjgh-2020-004181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908309PMC
February 2021

Cost-effectiveness of hepatitis C virus (HCV) elimination strategies among people who inject drugs (PWID) in Tijuana, Mexico.

Addiction 2021 Feb 23. Epub 2021 Feb 23.

University of California San Diego, La Jolla, CA, USA.

Background And Aims: In Latin America, Mexico was first to launch a hepatitis C virus (HCV) elimination strategy, where people who inject drugs (PWID) are a main risk group for transmission. In Tijuana, HCV seroprevalence among PWID is > 90%, with minimal harm reduction (HR). We evaluated cost-effectiveness of strategies to achieve the incidence elimination target among PWID in Tijuana.

Methods: Modeling study using a dynamic, cost-effectiveness model of HCV transmission and progression among active and former PWID in Tijuana, to assess the cost-effectiveness of incidence elimination strategies from a health-care provider perspective. The model incorporated PWID transitions between HR stages (no HR, only opioid agonist therapy, only high coverage needle-syringe programs, both). Four strategies that could achieve the incidence target (80% reduction by 2030) were compared with the status quo (no intervention). The strategies incorporated the number of direct-acting anti-viral (DAA) treatments required with: (1) no HR scale-up, (2) HR scale-up from 2019 to 20% coverage among PWID, (3) HR to 40% coverage and (4) HR to 50% coverage. Costs (2019 US$) and health outcomes [disability-adjusted life years (DALYs)] were discounted 3% per year. Mean incremental cost-effectiveness ratios (ICER, $/DALY averted) were compared with one-time per capita gross domestic product (GDP) ($9698 in 2019) and purchasing power parity-adjusted per capita GDP ($4842-13 557) willingness-to-pay (WTP) thresholds.

Results: DAAs alone were the least costly elimination strategy [$173 million, 95% confidence interval (CI) = 126-238 million], but accrued fewer health benefits compared with strategies with HR. DAAs + 50% HR coverage among PWID averted the most DALYs but cost $265 million, 95% CI = 210-335 million). The optimal strategy was DAAs + 50% HR (ICER $6743/DALY averted compared to DAAs only) under the one-time per-capita GDP WTP ($9698).

Conclusions: A combination of high-coverage harm reduction and hepatitis C virus treatment is the optimal cost-effective strategy to achieve the HCV incidence elimination goal in Mexico.
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http://dx.doi.org/10.1111/add.15456DOI Listing
February 2021

Impact of cumulative incarceration and the post-release period on syringe-sharing among people who inject drugs in Tijuana, Mexico: a longitudinal analysis.

Addiction 2021 Feb 23. Epub 2021 Feb 23.

Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Background And Aims: Syringe-sharing among people who inject drugs, which can occur during incarceration and post-release, has been linked with increased risk of blood-borne infections. We aimed to investigate the cumulative effect of repeated incarceration and the post-release period on receptive syringe-sharing.

Design: Ongoing community-based cohort, recruited through targeted sampling between 2011 and 2012 with 6-month follow-ups.

Setting: Tijuana, Mexico.

Participants: Sample of 185 participants (median age 35 years; 67% female) with no history of incarceration at study entry, followed to 2017.

Measurements: Cumulative incarceration and post-release period were constructed from incarceration events reported in the past 6 months for each study visit. Receptive syringe-sharing in the past 6 months was assessed as a binary variable. We used logistic regression with generalized estimating equations to examine the association between cumulative incarceration events and the post-release period with receptive syringe-sharing over time. Missing data were handled through multiple imputation.

Findings: At baseline, 65% of participants engaged in receptive syringe-sharing in the prior 6 months. At follow-up, 150 (81%) participants experienced a total of 358 incarceration events [median = 2, interquartile range (IQR) = 1-3]. The risk of receptive syringe-sharing increased with the number of repeated incarcerations. Compared with never incarcerated, those with one incarceration had 1.28 [95% confidence interval (CI) = 0.97-1.68] higher adjusted odds of syringe-sharing; two to three incarcerations, 1.42 (95% CI = 1.02-1.99) and more than three incarcerations, 2.10 (95% CI = 1.15-3.85). Participants released within the past 6 months had 1.53 (95% CI = 1.14-2.05) higher odds of sharing syringes compared with those never incarcerated. This post-release risk continued up to 1.5 years post-incarceration (adjusted odds ratio = 1.41, 95% CI = 1.04-1.91), but then waned.

Conclusions: A longitudinal community cohort study among people who inject drugs suggested that the effects of incarceration on increased injecting risk, measured through syringe-sharing, are cumulative and persist during the post-release period.
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http://dx.doi.org/10.1111/add.15445DOI Listing
February 2021

Screening for Sexually Transmitted Infections During Hepatitis C Treatment to Predict Reinfection Among People With HIV.

Open Forum Infect Dis 2021 Feb 30;8(2):ofaa643. Epub 2020 Dec 30.

Division of Infectious Diseases and Global Public Health, Department of Medicine, UC San Diego, San Diego, California, USA.

Background: Little is known about the risk of hepatitis C virus (HCV) reinfection among people with HIV (PWH) in the direct-acting antiviral (DAA) era. We evaluate HCV reinfection rates in the DAA era and characterize presustained virologic response (SVR) behavioral risk factors associated with reinfection among PWH at the University of California, San Diego (UCSD).

Methods: Observational longitudinal cohort of PWH treated with DAAs between 2014 and July 2019 who achieved SVR and had at least 1 subsequent HCV viral load measurement. HCV reinfection was defined as new HCV viremia after SVR. We examined whether screening for sexually transmitted infections (STIs) and substance use during the pre-SVR period could identify patients at greater risk for reinfection using exact Poisson regression to compare reinfection incidence rates between those with and without pre-SVR STIs and positive urine drug screens.

Results: Eight out of 200 PWH were reinfected with HCV a median ~26 weeks after SVR over 328.1 person-years of follow-up (PYFU), for an incidence rate of 2.44/100 PYFU. The observed HCV reinfection rate was highest among men who have sex with men who inject drugs (MSM IDU; 4.63/100 PFYU) and those aged 30-39 years (6.80/100 PYFU). Having a positive gonorrhea/chlamydia test during the pre-SVR period was a predictor of HCV reinfection.

Conclusions: The HCV reinfection rate in the DAA era is similar to the rate observed in the interferon era in San Diego in PWH. STI screening during HCV treatment may help determine those at higher risk for HCV reinfection.
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http://dx.doi.org/10.1093/ofid/ofaa643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850126PMC
February 2021

Evaluation of SARS-CoV-2 transmission mitigation strategies on a university campus using an agent-based network model.

Clin Infect Dis 2021 Jan 19. Epub 2021 Jan 19.

Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA, USA.

Universities are faced with decisions on how to resume campus activities while mitigating SARS-CoV-2 risk. To provide guidance for these decisions, we developed an agent-based network model of SARS-CoV-2 transmission to assess the potential impact of strategies to reduce outbreaks. The model incorporates important features related to risk at the University of California San Diego. We found that structural interventions for housing (singles only) and instructional changes (from in-person to hybrid with class size caps) can substantially reduce R0, but masking and social distancing are required to reduce this to at or below 1. Within a risk mitigation scenario, increased frequency of asymptomatic testing from monthly to twice weekly has minimal impact on average outbreak size (1.1-1.9), but substantially reduces the maximum outbreak size and cumulative number of cases. We conclude that an interdependent approach incorporating risk mitigation, viral detection, and public health intervention is required to mitigate risk.
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http://dx.doi.org/10.1093/cid/ciab037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929036PMC
January 2021

What the HIV Pandemic Experience Can Teach the United States About the COVID-19 Response.

J Acquir Immune Defic Syndr 2021 01;86(1):1-10

Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, CA; and.

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http://dx.doi.org/10.1097/QAI.0000000000002520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727321PMC
January 2021

What is required for achieving hepatitis C virus elimination in Singapore? A modeling study.

J Gastroenterol Hepatol 2021 Apr 3;36(4):1110-1117. Epub 2020 Sep 3.

Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California, USA.

Background And Aim: The vast majority of hepatitis C virus (HCV) infection in Singapore is among those with a history of injecting drug use (IDU), yet harm reduction is not available and what is required to achieve the World Health Organization (WHO) HCV elimination targets (80% incidence reduction and 65% mortality reduction by 2030) is unknown. We model the intervention scale-up required to achieve WHO targets in Singapore.

Methods: A dynamic model of HCV transmission and progression among those with a history of IDU was calibrated to Singapore, a setting with declining IDU and no harm reduction (~11 000 people with IDU history in 2017 and 45% HCV seropositive). We projected HCV treatment scale-up from 2019 required to achieve WHO targets with varying prioritization scenarios, with/without opiate substitution therapy scale-up (to 40% among people who inject drugs [PWID]).

Results: We estimated 3855 (95% confidence interval: 2635-5446) chronically HCV-infected individuals with a history of IDU and 148 (87-284) incident HCV cases in Singapore in 2019. Reaching the HCV incidence target requires 272 (187-384) treatments in 2019, totaling 2444 (1683-3452) across 2019-2030. By prioritizing PWID or PWID and cirrhotics, 60% or 30% fewer treatments are required, respectively, whereas the target cannot be achieved with cirrhosis prioritization. Opiate substitution therapy scale-up reduces treatments required by 21-24%. Achieving both WHO targets requires treating 631 (359-1047) in 2019, totaling 3816 (2664-5423) across 2019-2030.

Conclusions: Hepatitis C virus elimination is achievable in Singapore but even with declining IDU requires immediate treatment scale-up among PWID. Harm reduction provision reduces treatments required and provides additional benefits.
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http://dx.doi.org/10.1111/jgh.15211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174139PMC
April 2021

Cost-effectiveness of using hepatitis C viremic hearts for transplantation into HCV-negative recipients.

Am J Transplant 2021 02 15;21(2):657-668. Epub 2020 Sep 15.

Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California.

Outcomes following hepatitis C virus (HCV)-viremic heart transplantation into HCV-negative recipients with HCV treatment are good. We assessed cost-effectiveness between cohorts of transplant recipients willing and unwilling to receive HCV-viremic hearts. Markov model simulated long-term outcomes among HCV-negative patients on the transplant waitlist. We compared costs (2018 USD) and health outcomes (quality-adjusted life-years, QALYs) between cohorts willing to accept any heart and those willing to accept only HCV-negative hearts. We assumed 4.9% HCV-viremic donor prevalence. Patients receiving HCV-viremic hearts were treated, assuming $39 600/treatment with 95% cure. Incremental cost-effectiveness ratios (ICERs) were compared to a $100 000/QALY gained willingness-to-pay threshold. Sensitivity analyses included stratification by blood type or region and potential negative consequences of receipt of HCV-viremic hearts. Compared to accepting only HCV-negative hearts, accepting any heart gained 0.14 life-years and 0.11 QALYs, while increasing costs by $9418/patient. Accepting any heart was cost effective (ICER $85 602/QALY gained). Results were robust to all transplant regions and blood types, except type AB. Accepting any heart remained cost effective provided posttransplant mortality and costs among those receiving HCV-viremic hearts were not >7% higher compared to HCV-negative hearts. Willingness to accept HCV-viremic hearts for transplantation into HCV-negative recipients is cost effective and improves clinical outcomes.
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http://dx.doi.org/10.1111/ajt.16245DOI Listing
February 2021

What is needed to achieve HCV microelimination among HIV-infected populations in Andalusia, Spain: a modeling analysis.

BMC Infect Dis 2020 Aug 8;20(1):588. Epub 2020 Aug 8.

Division of Infectious Diseases and Global Public Health, University of California San Diego, 9500 Gilman Drive MC 0507, La Jolla, CA, 92093, USA.

Background: Scale-up of hepatitis C virus (HCV) treatment for HIV/HCV coinfected individuals is occurring in Spain, the vast majority (> 85%) with a reported history of injecting drug use and a smaller population of co-infected men who have sex with men (MSM). We assess impact of recent treatment scale-up to people living with HIV (PLWH) and implications for achieving the WHO HCV incidence elimination target (80% reduction 2015-2030) among PLWH and overall in Andalusia, Spain, using dynamic modeling.

Methods: A dynamic transmission model of HCV/HIV coinfection was developed. The model was stratified by people who inject drugs (PWID) and MSM. The PWID component included dynamic HCV transmission from the HCV-monoinfected population. The model was calibrated to Andalusia based on published data and the HERACLES cohort (prospective cohort of HIV/HCV coinfected individuals representing > 99% coinfected individuals in care in Andalusia). From HERACLES, we incorporated HCV treatment among diagnosed PLWH of 10.5%/year from 2004 to 2014, and DAAs at 33%/year from 2015 with 94.8% SVR. We project the impact of current and scaled-up HCV treatment for PLWH on HCV prevalence and incidence among PLWH and overall.

Results: Current treatment rates among PLWH (scaled-up since 2015) could substantially reduce the number of diagnosed coinfected individuals (mean 76% relative reduction from 2015 to 2030), but have little impact on new diagnosed coinfections (12% relative reduction). However, DAA scale-up to PWLH in 2015 would have minimal future impact on new diagnosed coinfections (mean 9% relative decrease from 2015 to 2030). Similarly, new cases of HCV would only reduce by a mean relative 29% among all PWID and MSM due to ongoing infection/reinfection. Diagnosing/treating all PLWH annually from 2020 would increase the number of new HCV infections among PWLH by 28% and reduce the number of new HCV infections by 39% among the broader population by 2030.

Conclusion: Targeted scale-up of HCV treatment to PLWH can dramatically reduce prevalence among this group but will likely have little impact on the annual number of newly diagnosed HIV/HCV coinfections. HCV microelimination efforts among PWLH in Andalusia and settings where a large proportion of PLWH have a history of injecting drug use will require scaled-up HCV diagnosis and treatment among PLWH and the broader population at risk.
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http://dx.doi.org/10.1186/s12879-020-05285-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414743PMC
August 2020

Estimating the contribution of stimulant injection to HIV and HCV epidemics among people who inject drugs and implications for harm reduction: A modeling analysis.

Drug Alcohol Depend 2020 Jun 24;213:108135. Epub 2020 Jun 24.

Division of Infectious Diseases and Global Public Health, University of California San Diego, USA; Population Health Sciences, Bristol Medical School, University of Bristol, UK.

Background: Stimulants, such as amphetamines and cocaine, are widely injected among people who inject drugs (PWID). Systematic reviews indicate stimulant injection is associated with HIV and HCV among PWID. Using these associations, we estimated the contribution of stimulant injection to HIV and HCV transmission among PWID.

Methods: We modeled HIV and HCV transmission among PWID, incorporating excess injecting and sexual risk among PWID who inject stimulants. We simulated three illustrative settings with different stimulants injected, prevalence of stimulant injecting, and HIV/HCV epidemiology. We estimated one-year population attributable fractions of stimulant injection on new HIV and HCV infections, and impact of scaling up needle-syringe programs (NSP).

Results: In low prevalence settings of stimulant injection (St. Petersburg-like, where 13 % inject amphetamine), 9% (2.5-97.5 % interval [95 %I]: 6-15 %) and 7% (95 %I 4-11 %) of incident HIV and HCV cases, respectively, could be associated with stimulant injection in the next year. With moderate stimulant injection (Montreal-like, where 34 % inject cocaine), 29 % (95 %I: 19-37 %) and 19 % (95 %I: 16-21 %) of incident HIV and HCV cases, respectively, could be associated with stimulant injection. In high-burden settings like Bangkok where 65 % inject methamphetamine, 23 % (95%I:10-34%) and 20 % (95%I: 9-27%) of incident HIV and HCV cases could be due to stimulant injection. High-coverage NSP (60 %) among PWID who inject stimulants could reduce HIV (by 22-65 %) and HCV incidence (by 7-11 %) in a decade.

Discussion: Stimulant injection contributes substantially to HIV and HCV among PWID. NSP scale-up and development of novel interventions among PWID who inject stimulants are warranted.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829087PMC
June 2020

Modelling integrated antiretroviral treatment and harm reduction services on HIV and overdose among people who inject drugs in Tijuana, Mexico.

J Int AIDS Soc 2020 06;23 Suppl 1:e25493

Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, CA, USA.

Introduction: The HIV epidemic in Tijuana, Mexico is concentrated in key populations, including people who inject drugs (PWID). However, HIV interventions among PWID are minimal, and federal funding was provided for compulsory abstinence programmes associated with HIV and overdose. Alternatively, opioid agonist therapy reduces overdose, reincarceration, HIV, while improving antiretroviral therapy (ART) outcomes. We assessed potential impact and synergies of scaled-up integrated ART and opioid agonist therapy, compared to scale-up of each separately, and potential harms of compulsory abstinence programmes on HIV and fatal overdose among PWID in Tijuana.

Methods: We developed a dynamic model of HIV transmission and overdose among PWID in Tijuana. We simulated scale-up of opioid agonist therapy from zero to 40% coverage among PWID. We evaluated synergistic benefits of an integrated harm reduction and ART scale-up strategy (40% opioid agonist therapy coverage and 10-fold ART recruitment), compared to scale-up of each intervention alone or no scale-up of low coverage ART and no harm reduction). We additionally simulated compulsory abstinence programmes (associated with 14% higher risk of receptive syringe sharing and 76% higher odds of overdose) among PWID.

Results: Without intervention, HIV incidence among PWID could increase from 0.72 per 100 person-years (PY) in 2020 to 0.92 per 100 PY in 2030. Over ten years, opioid agonist therapy scale-up could avert 31% (95% uncertainty interval (UI): 18%, 46%) and 22% (95% UI: 10%, 28%) new HIV infections and fatal overdoses, respectively, with the majority of HIV impact from the direct effect on HIV transmission due to low ART coverage. Integrating opioid agonist therapy and ART scale-up provided synergistic benefits, with opioid agonist therapy effects on ART recruitment/retention averting 9% more new infections compared to ART scale-up alone. The intervention strategy could avert 48% (95% UI: 26%, 68%) of new HIV infections and one-fifth of fatal overdoses over ten years. Conversely, compulsory abstinence programmes could increase HIV and overdoses.

Conclusions: Integrating ART with opioid agonist therapy could provide synergistic benefits and prevent HIV and overdoses among PWID in Tijuana, whereas compulsory abstinence programmes could cause harm. Policymakers should consider the benefits of integrating harm reduction and HIV services for PWID.
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http://dx.doi.org/10.1002/jia2.25493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305416PMC
June 2020

Modelling integrated antiretroviral treatment and harm reduction services on HIV and overdose among people who inject drugs in Tijuana, Mexico.

J Int AIDS Soc 2020 06;23 Suppl 1:e25493

Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, CA, USA.

Introduction: The HIV epidemic in Tijuana, Mexico is concentrated in key populations, including people who inject drugs (PWID). However, HIV interventions among PWID are minimal, and federal funding was provided for compulsory abstinence programmes associated with HIV and overdose. Alternatively, opioid agonist therapy reduces overdose, reincarceration, HIV, while improving antiretroviral therapy (ART) outcomes. We assessed potential impact and synergies of scaled-up integrated ART and opioid agonist therapy, compared to scale-up of each separately, and potential harms of compulsory abstinence programmes on HIV and fatal overdose among PWID in Tijuana.

Methods: We developed a dynamic model of HIV transmission and overdose among PWID in Tijuana. We simulated scale-up of opioid agonist therapy from zero to 40% coverage among PWID. We evaluated synergistic benefits of an integrated harm reduction and ART scale-up strategy (40% opioid agonist therapy coverage and 10-fold ART recruitment), compared to scale-up of each intervention alone or no scale-up of low coverage ART and no harm reduction). We additionally simulated compulsory abstinence programmes (associated with 14% higher risk of receptive syringe sharing and 76% higher odds of overdose) among PWID.

Results: Without intervention, HIV incidence among PWID could increase from 0.72 per 100 person-years (PY) in 2020 to 0.92 per 100 PY in 2030. Over ten years, opioid agonist therapy scale-up could avert 31% (95% uncertainty interval (UI): 18%, 46%) and 22% (95% UI: 10%, 28%) new HIV infections and fatal overdoses, respectively, with the majority of HIV impact from the direct effect on HIV transmission due to low ART coverage. Integrating opioid agonist therapy and ART scale-up provided synergistic benefits, with opioid agonist therapy effects on ART recruitment/retention averting 9% more new infections compared to ART scale-up alone. The intervention strategy could avert 48% (95% UI: 26%, 68%) of new HIV infections and one-fifth of fatal overdoses over ten years. Conversely, compulsory abstinence programmes could increase HIV and overdoses.

Conclusions: Integrating ART with opioid agonist therapy could provide synergistic benefits and prevent HIV and overdoses among PWID in Tijuana, whereas compulsory abstinence programmes could cause harm. Policymakers should consider the benefits of integrating harm reduction and HIV services for PWID.
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http://dx.doi.org/10.1002/jia2.25493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305416PMC
June 2020

The use of mathematical modeling to inform drug policy making.

Int J Drug Policy 2021 Feb 17;88:102759. Epub 2020 Apr 17.

Population Health Sciences, University of Bristol, UK.

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http://dx.doi.org/10.1016/j.drugpo.2020.102759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164851PMC
February 2021

Cost-Effectiveness of Antenatal Rescreening Among Pregnant Women for Hepatitis C in the United States.

Clin Infect Dis 2020 Apr 13. Epub 2020 Apr 13.

Division of Infectious Diseases and Global Public Health, University of California San Diego, CA.

To inform proposed changes in U.S. HCV screening guidelines, we assessed the cost-effectiveness of HCV antenatal rescreening for women without evidence of HCV during a prior pregnancy, using a previously published model. Universal HCV rescreening among pregnant women was cost-effective (ICER $6,000/QALY) and should be recommended nationally.
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http://dx.doi.org/10.1093/cid/ciaa362DOI Listing
April 2020

Is hepatitis C virus (HCV) elimination achievable among people who inject drugs in Tijuana, Mexico? A modeling analysis.

Int J Drug Policy 2021 Feb 9;88:102710. Epub 2020 Mar 9.

Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California, United States; Population Health Sciences, University of Bristol, Bristol, United Kingdom.

Background: In 2019, Mexico became the first Latin American country committed to hepatitis C virus (HCV) elimination, but the amount of intervention scale-up required is unclear. In Tijuana, HCV among people who inject drugs (PWID) is high; yet there is minimal and intermittent harm reduction, and involuntary exposure to compulsory abstinence programs (CAP) occurs which is associated with increased HCV risk. We determined what combination intervention scale-up can achieve HCV elimination among current and former PWID in Tijuana.

Methods: We constructed a dynamic, deterministic model of HCV transmission, disease progression, and harm reduction among current and former PWID parameterized to Tijuana (~10,000 current PWID, 90% HCV seropositive, minimal opiate agonist therapy [OAT] or high coverage needle/syringe programs [HCNSP]). We evaluated the number of direct-acting antiviral (DAA) treatments needed from 2019 to achieve elimination targets (80% incidence reduction, 65% mortality reduction by 2030) with: (a) DAAs alone, (b) DAAs plus scale-up of OAT+HCNSP (up to 50% coverage of OAT and HCNSP separately, producing 25% of PWID receiving both), (c) DAAs plus CAP scale-up to 50%. Scenarios examined the number of DAAs required if prioritized to current PWID or provided regardless of current injection status, and impact of harm reduction interruptions.

Results: Modeling suggests among ~30,000 current and former PWID in Tijuana, 16,160 (95%CI: 12,770-21,610) have chronic HCV. DAA scale-up can achieve the incidence target, requiring 770 treatments/year (95%CI: 640-970) if prioritized to current PWID. 40% fewer DAAs are required with OAT+HCNSP scale-up to 50% among PWID, whereas more are required with involuntary CAP scale-up. Both targets can only be achieved through treating both current and former PWID (1,710 treatments/year), and impact is reduced with harm reduction interruptions.

Conclusions: Elimination targets are achievable in Tijuana through scale-up of harm reduction and DAA therapy, whereas involuntary CAP and harm reduction interruptions hamper elimination.
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http://dx.doi.org/10.1016/j.drugpo.2020.102710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133359PMC
February 2021

Scaling up screening and treatment for elimination of hepatitis C among men who have sex with men in the era of HIV pre-exposure prophylaxis.

EClinicalMedicine 2020 Feb 19;19:100217. Epub 2019 Dec 19.

University of Bristol, Oakfield House, Oakfield Grove BS8 2BN, UK.

Background: Routine HIV pre-exposure prophylaxis (PrEP) and HIV care appointments provide opportunities for screening men who have sex with men (MSM) for hepatitis C virus infection (HCV). However, levels of screening required for achieving the WHO elimination target of reducing HCV incidence by 90% by 2030 among all MSM are unknown.

Methods: An HCV/HIV transmission model was calibrated to UK prevalence of HIV among MSM (4·7%) and chronic HCV infection among HIV-positive MSM (9·9%) and HIV-negative MSM (1.2%). Assuming 12·5% coverage of PrEP among HIV-negative MSM, we evaluated the relative reduction in overall HCV incidence by 2030 (compared to 2018 levels) of HCV screening every 12/6-months (alongside completing direct acting antiviral treatment within 6-months of diagnosis) in PrEP users and/or HIV-diagnosed MSM. We estimated the additional screening required among HIV-negative non-PrEP users to reduce overall incidence by 90% by 2030. The effect of 50% reduction in condom use among PrEP users (risk compensation) was estimated.

Results: Screening and treating PrEP users for HCV every 12 or 6-months decreases HCV incidence by 67·3% (uncertainty range 52·7-79·2%) or 70·2% (57·1-80·8%), respectively, increasing to 75·4% (59·0-88·6%) or 78·8% (63·9-90·4%) if HIV-diagnosed MSM are also screened at same frequencies. Risk compensation reduces these latter projections by <10%. To reduce HCV incidence by 90% by 2030 without risk compensation, HIV-negative non-PrEP users require screening every 5·6 (3·8-9·2) years if MSM on PrEP and HIV-diagnosed MSM are screened every 6-months, shortening to 4·4 (3·1-6·6) years with risk compensation. For 25·0% PrEP coverage, the HCV elimination target can be reached without screening HIV-negative MSM not on PrEP, irrespective of risk compensation.

Interpretation: At low PrEP coverage, increased screening of all MSM is required to achieve the WHO HCV-elimination targets for MSM in the UK, whereas at higher PrEP coverage this is possible through just screening HIV-diagnosed MSM and PrEP users.
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http://dx.doi.org/10.1016/j.eclinm.2019.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046521PMC
February 2020

Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis.

Lancet Glob Health 2020 03;8(3):e440-e450

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Background: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence.

Methods: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs.

Findings: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13·8 million (95% UI 13·4-14·1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26·5% (22·5-30·7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged ≥30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46·8% and decrease incidence by 50·8% (95% UI 46·1-55·0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8·1 billion, reducing to $3·9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm.

Interpretation: Pakistan will need to invest about 9·0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030.

Funding: UNITAID.
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http://dx.doi.org/10.1016/S2214-109X(20)30003-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295205PMC
March 2020

Prisons can also improve drug user health in the community.

Addiction 2020 05 5;115(5):914-915. Epub 2020 Feb 5.

Population Health Sciences, University of Bristol, Bristol, UK.

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http://dx.doi.org/10.1111/add.14971DOI Listing
May 2020

Cost-effectiveness of the HepCATT intervention in specialist drug clinics to improve case-finding and engagement with HCV treatment for people who inject drugs in England.

Addiction 2020 08 11;115(8):1509-1521. Epub 2020 Feb 11.

Population Health Sciences, Bristol Medical School, University of Bristol, UK.

Background And Aims: People who inject drugs (PWID) are at high risk of hepatitis C virus (HCV) infection; however, ~50% are undiagnosed in England and linkage-to-care is poor. This study investigated the cost-effectiveness of an intervention (HepCATT) to improve case-finding and referral to HCV treatment compared with standard-of-care pathways in drug treatment centres in England.

Design: HCV transmission and disease progression model with cost-effectiveness analysis using a health-care perspective. Primary outcome and cost data from the HepCATT study parameterized the intervention, suggesting that HepCATT increased HCV testing in drug treatment centres 2.5-fold and engagement onto the HCV treatment pathway 10-fold. A model was used to estimate the decrease in HCV infections and HCV-related deaths from 2016, with costs and health benefits (quality-adjusted life-years or QALYs) tracked over 50 years. Univariable and probabilistic sensitivity analyses (PSA) were undertaken.

Setting: England-specific epidemic with 40% prevalence of chronic HCV among PWID.

Participants: PWID attending drug treatment centres.

Intervention: Nurse facilitator in drug treatment centres to improve the HCV care pathway from HCV case-finding to referral and linkage to specialist care. Comparator was the standard-of-care HCV care pathway.

Measurements: Incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained through improved case-finding.

Findings: Over 50 years per 1000 PWID, the HepCATT intervention could prevent 75 (95% central interval 37-129) deaths and 1330 (827-2040) or 51% (30-67%) of all new infections. The mean ICER was £7986 per QALY gained, with all PSA simulations being cost-effective at a £20 000 per QALY willingness-to-pay threshold. Univariable sensitivity analyses suggest the intervention would become cost-saving if the cost of HCV treatment reduces to £3900. If scaled up to all PWID in England, the intervention would cost £8.8 million and decrease incidence by 56% (33-70%) by 2030.

Conclusions: Increasing hepatitis C virus infection case-finding and treatment referral in drug treatment centres could be a highly cost-effective strategy for decreasing hepatitis C virus incidence among people who inject drugs.
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http://dx.doi.org/10.1111/add.14978DOI Listing
August 2020

Interim effect evaluation of the hepatitis C elimination programme in Georgia: a modelling study.

Lancet Glob Health 2020 02 18;8(2):e244-e253. Epub 2019 Dec 18.

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Background: Georgia has a high prevalence of hepatitis C, with 5·4% of adults chronically infected. On April 28, 2015, Georgia launched a national programme to eliminate hepatitis C by 2020 (90% reduction in prevalence) through scaled-up treatment and prevention interventions. We evaluated the interim effect of the programme and feasibility of achieving the elimination goal.

Methods: We developed a transmission model to capture the hepatitis C epidemic in Georgia, calibrated to data from biobehavioural surveys of people who inject drugs (PWID; 1998-2015) and a national survey (2015). We projected the effect of the administration of direct-acting antiviral treatments until Feb 28, 2019, and the effect of continuing current treatment rates until the end of 2020. Effect was estimated in terms of the relative decrease in hepatitis C incidence, prevalence, and mortality relative to 2015 and of the deaths and infections averted compared with a counterfactual of no treatment over the study period. We also estimated treatment rates needed to reach Georgia's elimination target.

Findings: From May 1, 2015, to Feb 28, 2019, 54 313 patients were treated, with approximately 1000 patients treated per month since mid 2017. Compared with 2015, our model projects that these treatments have reduced the prevalence of adult chronic hepatitis C by a median 37% (95% credible interval 30-44), the incidence of chronic hepatitis C by 37% (29-44), and chronic hepatitis C mortality by 14% (3-30) and have prevented 3516 (1842-6250) new infections and averted 252 (134-389) deaths related to chronic hepatitis C. Continuing treatment of 1000 patients per month is predicted to reduce prevalence by 51% (42-61) and incidence by 51% (40-62), by the end of 2020. To reach a 90% reduction by 2020, treatment rates must increase to 4144 (2963-5322) patients initiating treatment per month.

Interpretation: Georgia's hepatitis C elimination programme has achieved substantial treatment scale-up, which has reduced the burden of chronic hepatitis C. However, the country is unlikely to meet its 2020 elimination target unless treatment scales up considerably.

Funding: CDC Foundation, National Institute for Health Research, National Institutes of Health.
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http://dx.doi.org/10.1016/S2214-109X(19)30483-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025283PMC
February 2020

Opioid agonist treatment scale-up and the initiation of injection drug use: A dynamic modeling analysis.

PLoS Med 2019 11 26;16(11):e1002973. Epub 2019 Nov 26.

Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California, United States of America.

Background: Injection drug use (IDU) is associated with multiple health harms. The vast majority of IDU initiation events (in which injection-naïve persons first adopt IDU) are assisted by a person who injects drugs (PWID), and as such, IDU could be considered as a dynamic behavioral transmission process. Data suggest that opioid agonist treatment (OAT) enrollment is associated with a reduced likelihood of assisting with IDU initiation. We assessed the association between recent OAT enrollment and assisting IDU initiation across several North American settings and used dynamic modeling to project the potential population-level impact of OAT scale-up within the PWID population on IDU initiation.

Methods And Findings: We employed data from a prospective multicohort study of PWID in 3 settings (Vancouver, Canada [n = 1,737]; San Diego, United States [n = 346]; and Tijuana, Mexico [n = 532]) from 2014 to 2017. Site-specific modified Poisson regression models were constructed to assess the association between recent (past 6 month) OAT enrollment and history of ever having assisted an IDU initiation with recently assisting IDU initiation. Findings were then pooled using linear mixed-effects techniques. A dynamic transmission model of IDU among the general population was developed, stratified by known factors associated with assisting IDU initiation and relevant drug use behaviors. The model was parameterized to a generic North American setting (approximately 1% PWID) and used to estimate the impact of increasing OAT coverage among PWID from baseline (approximately 21%) to 40%, 50%, and 60% on annual IDU initiation incidence and corresponding PWID population size across a decade. From Vancouver, San Diego, and Tijuana, respectively, 4.5%, 5.2%, and 4.3% of participants reported recently assisting an IDU initiation, and 49.4%, 19.7%, and 2.1% reported recent enrollment in OAT. Recent OAT enrollment was significantly associated with a 45% lower likelihood of providing recent IDU initiation assistance among PWID (relative risk [RR] 0.55 [95% CI 0.36-0.84], p = 0.006) compared to those not recently on OAT. Our dynamic model predicts a baseline mean of 1,067 (2.5%-97.5% interval [95% I 490-2,082]) annual IDU initiations per 1,000,000 individuals, of which 886 (95% I 406-1,750) are assisted by PWID. Based on our observed statistical associations, our dynamic model predicts that increasing OAT coverage from approximately 21% to 40%, 50%, or 60% among PWID could reduce annual IDU initiations by 11.5% (95% I 2.4-21.7), 17.3% (95% I 5.6-29.4), and 22.8% (95% I 8.1-36.8) and reduce the PWID population size by 5.4% (95% I 0.1-12.0), 8.2% (95% I 2.2-16.9), and 10.9% (95% I 3.2-21.8) relative to baseline, respectively, in a decade. Less impact occurs when the protective effect of OAT is diminished, when a greater proportion of IDU initiations are unassisted by PWID, and when average IDU career length is longer. The study's main limitations are uncertainty in the causal pathway between OAT enrollment and assisting with IDU initiation and the use of a simplified model of IDU initiation.

Conclusions: In addition to its known benefits on preventing HIV, hepatitis C virus (HCV), and overdose among PWID, our modeling suggests that OAT scale-up may also reduce the number of IDU initiations and PWID population size.
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http://dx.doi.org/10.1371/journal.pmed.1002973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879119PMC
November 2019

Opioid agonist treatment scale-up and the initiation of injection drug use: A dynamic modeling analysis.

PLoS Med 2019 11 26;16(11):e1002973. Epub 2019 Nov 26.

Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California, United States of America.

Background: Injection drug use (IDU) is associated with multiple health harms. The vast majority of IDU initiation events (in which injection-naïve persons first adopt IDU) are assisted by a person who injects drugs (PWID), and as such, IDU could be considered as a dynamic behavioral transmission process. Data suggest that opioid agonist treatment (OAT) enrollment is associated with a reduced likelihood of assisting with IDU initiation. We assessed the association between recent OAT enrollment and assisting IDU initiation across several North American settings and used dynamic modeling to project the potential population-level impact of OAT scale-up within the PWID population on IDU initiation.

Methods And Findings: We employed data from a prospective multicohort study of PWID in 3 settings (Vancouver, Canada [n = 1,737]; San Diego, United States [n = 346]; and Tijuana, Mexico [n = 532]) from 2014 to 2017. Site-specific modified Poisson regression models were constructed to assess the association between recent (past 6 month) OAT enrollment and history of ever having assisted an IDU initiation with recently assisting IDU initiation. Findings were then pooled using linear mixed-effects techniques. A dynamic transmission model of IDU among the general population was developed, stratified by known factors associated with assisting IDU initiation and relevant drug use behaviors. The model was parameterized to a generic North American setting (approximately 1% PWID) and used to estimate the impact of increasing OAT coverage among PWID from baseline (approximately 21%) to 40%, 50%, and 60% on annual IDU initiation incidence and corresponding PWID population size across a decade. From Vancouver, San Diego, and Tijuana, respectively, 4.5%, 5.2%, and 4.3% of participants reported recently assisting an IDU initiation, and 49.4%, 19.7%, and 2.1% reported recent enrollment in OAT. Recent OAT enrollment was significantly associated with a 45% lower likelihood of providing recent IDU initiation assistance among PWID (relative risk [RR] 0.55 [95% CI 0.36-0.84], p = 0.006) compared to those not recently on OAT. Our dynamic model predicts a baseline mean of 1,067 (2.5%-97.5% interval [95% I 490-2,082]) annual IDU initiations per 1,000,000 individuals, of which 886 (95% I 406-1,750) are assisted by PWID. Based on our observed statistical associations, our dynamic model predicts that increasing OAT coverage from approximately 21% to 40%, 50%, or 60% among PWID could reduce annual IDU initiations by 11.5% (95% I 2.4-21.7), 17.3% (95% I 5.6-29.4), and 22.8% (95% I 8.1-36.8) and reduce the PWID population size by 5.4% (95% I 0.1-12.0), 8.2% (95% I 2.2-16.9), and 10.9% (95% I 3.2-21.8) relative to baseline, respectively, in a decade. Less impact occurs when the protective effect of OAT is diminished, when a greater proportion of IDU initiations are unassisted by PWID, and when average IDU career length is longer. The study's main limitations are uncertainty in the causal pathway between OAT enrollment and assisting with IDU initiation and the use of a simplified model of IDU initiation.

Conclusions: In addition to its known benefits on preventing HIV, hepatitis C virus (HCV), and overdose among PWID, our modeling suggests that OAT scale-up may also reduce the number of IDU initiations and PWID population size.
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http://dx.doi.org/10.1371/journal.pmed.1002973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879119PMC
November 2019

Modelling the potential prevention benefits of a treat-all hepatitis C treatment strategy at global, regional and country levels: A modelling study.

J Viral Hepat 2019 12 30;26(12):1388-1403. Epub 2019 Aug 30.

Population Health Sciences, University of Bristol, Bristol, UK.

The World Health Organization (WHO) recently produced guidelines advising a treat-all policy for HCV to encourage widespread treatment scale-up for achieving HCV elimination. We modelled the prevention impact achieved (HCV infections averted [IA]) from initiating this policy compared with treating different subgroups at country, regional and global levels. We assessed what country-level factors affect impact. A dynamic, deterministic HCV transmission model was calibrated to data from global systematic reviews and UN data sets to simulate country-level HCV epidemics with ongoing levels of treatment. For each country, the model projected the prevention impact (in HCV IA per treatment undertaken) of initiating four treatment strategies; either selected randomly (treat-all) or targeted among people who inject drugs (PWID), people aged ≥35, or those with cirrhosis. The IA was assessed over 20 years. Linear regression was used to identify associations between IA per treatment and demographic factors. Eighty-eight countries (85% of the global population) were modelled. Globally, the model estimated 0.35 (95% credibility interval [95%CrI]: 0.16-0.61) IA over 20 years for every randomly allocated treatment, 0.30 (95%CrI: 0.12-0.53) from treating those aged ≥35 and 0.28 (95%CrI: 0.12-0.49) for those with cirrhosis. Globally, treating PWID achieved 1.27 (95%CrI: 0.68-2.04) IA per treatment. The IA per randomly allocated treatment was positively associated with a country's population growth rate and negatively associated with higher HCV prevalence among PWID. In conclusion, appreciable prevention benefits could be achieved from WHO's treat-all strategy, although greater benefits per treatment can be achieved through targeting PWID. Higher impact will be achieved in countries with high population growth.
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http://dx.doi.org/10.1111/jvh.13187DOI Listing
December 2019

Eliminating Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men in Berlin: A Modeling Analysis.

J Infect Dis 2019 10;220(10):1635-1644

Center for Infectiology, Berlin, Germany.

Background: Despite high hepatitis C virus (HCV) treatment rates, HCV incidence among human immunodeficiency virus (HIV)-infected men who have sex with men (HIV-infected MSM) in Germany rose before HCV direct-acting antivirals (DAAs). We model what intervention can achieve the World Health Organization (WHO) elimination target of an 80% reduction in HCV incidence by 2030 among HIV-infected MSM in Berlin.

Methods: An HCV transmission model among HIV-diagnosed MSM was calibrated to Berlin (rising HCV incidence and high rates of HCV testing and treatment). We modeled the HCV incidence among HIV-diagnosed MSM in Berlin until 2030 (relative to 2015 WHO baseline) under scenarios of DAA scale-up with or without behavior change (among HIV-diagnosed MSM and/or all MSM).

Results: Continuing current treatment rates will marginally reduce the HCV incidence among HIV-diagnosed MSM in Berlin by 2030. Scaling up DAA treatment rates, beginning in 2018, to 100% of newly diagnosed HCV infections within 3 months of diagnosis and 25% each year of previously diagnosed and untreated HCV infections could reduce the HCV incidence by 61% (95% confidence interval, 55.4%-66.7%) by 2030. The WHO target would likely be achieved by combining DAA scale-up with a 40% reduction in HCV transmission among HIV-diagnosed MSM and a 20% reduction among HIV-undiagnosed or HIV-uninfected MSM.

Discussion: HCV elimination among HIV-infected MSM in Berlin likely requires combining DAA scale-up with moderately effective behavioral interventions to reduce risk among all MSM.
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Source
http://dx.doi.org/10.1093/infdis/jiz367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360352PMC
October 2019