We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect ...of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Background and Aims
The individual‐level effectiveness of opioid agonist treatment (OAT) in reducing mortality is well established, but there is less evidence on population‐level benefits. We use ...modeling informed with linked data from the OAT program in New South Wales (NSW), Australia, to estimate the impact of OAT provision in the community and prisons on mortality and the impact of eliminating excess mortality during OAT initiation/discontinuation.
Design
Dynamic modeling.
Setting and participants
A cohort of 49 359 individuals who ever received OAT in NSW from 2001 to 2018.
Measurements
Receipt of OAT was represented through five stages: (i) first month on OAT, (ii) short (1–9 months) and (iii) longer (9+ months) duration on OAT, (iv) first month following OAT discontinuation and (v) rest of time following OAT discontinuation. Incarceration was represented as four strata: (i) never or not incarcerated in the past year, (ii) currently incarcerated, (iii) released from prison within the past month and (iv) released from prison 1–12 months ago. The model incorporated elevated mortality post‐release from prison and OAT impact on reducing mortality and incarceration.
Findings
Among the cohort, mortality was 0.9 per 100 person‐years, OAT coverage and retention remained high (> 50%, 1.74 years/episode). During 2001–20, we estimate that OAT provision reduced overdose and other cause mortality among the cohort by 52.8% 95% credible interval (CrI) = 49.4–56.9% and 26.6% (95% CrI =22.1–30.5%), respectively. We estimate 1.2 deaths averted and 9.7 life‐years gained per 100 person‐years on OAT. Prison OAT with post‐release OAT‐linkage accounted for 12.4% (95% CrI = 11.5–13.5%) of all deaths averted by the OAT program, primarily through preventing deaths in the first month post‐release. Preventing elevated mortality during OAT initiation and discontinuation could have averted up to 1.4% (95% CrI = 0.8–2.0%) and 3.0% (95% CrI = 2.1–5.3%) of deaths, respectively.
Conclusion
The community and prison opioid agonist treatment program in New South Wales, Australia appears to have substantially reduced population‐level overdose and all‐cause mortality in the past 20 years, partially due to high retention.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The opioid crisis in the United States has been defined by waves of drug- and locality-specific Opioid use-Related Epidemics (OREs) of overdose and bloodborne infections, among a range of health ...harms. The ability to identify localities at risk of such OREs, and better yet, to predict which ones will experience them, holds the potential to mitigate further morbidity and mortality. This narrative review was conducted to identify and describe quantitative approaches aimed at the “risk assessment,” “detection” or “prediction” of OREs in the United States. We implemented a PubMed search composed of the: (1) objective (eg, prediction), (2) epidemiologic outcome (eg, outbreak), (3) underlying cause (ie, opioid use), (4) health outcome (eg, overdose, HIV), (5) location (ie, US). In total, 46 studies were included, and the following information extracted: discipline, objective, health outcome, drug/substance type, geographic region/unit of analysis, and data sources. Studies identified relied on clinical, epidemiological, behavioral and drug markets surveillance and applied a range of methods including statistical regression, geospatial analyses, dynamic modeling, phylogenetic analyses and machine learning. Studies for the prediction of overdose mortality at national/state/county and zip code level are rapidly emerging. Geospatial methods are increasingly used to identify hotspots of opioid use and overdose. In the context of infectious disease OREs, routine genetic sequencing of patient samples to identify growing transmission clusters via phylogenetic methods could increase early detection capacity. A coordinated implementation of multiple, complementary approaches would increase our ability to successfully anticipate outbreak risk and respond preemptively. We present a multi-disciplinary framework for the prediction of OREs in the US and reflect on challenges research teams will face in implementing such strategies along with good practices.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Programmatic planning in HIV requires estimates of the distribution of new HIV infections according to identifiable characteristics of individuals. In sub-Saharan Africa, robust routine data sources ...and historical epidemiological observations are available to inform and validate such estimates.
We developed a predictive model, the Incidence Patterns Model (IPM), representing populations according to factors that have been demonstrated to be strongly associated with HIV acquisition risk: gender, marital/sexual activity status, geographic location, "key populations" based on risk behaviours (sex work, injecting drug use, and male-to-male sex), HIV and ART status within married or cohabiting unions, and circumcision status. The IPM estimates the distribution of new infections acquired by group based on these factors within a Bayesian framework accounting for regional prior information on demographic and epidemiological characteristics from trials or observational studies. We validated and trained the model against direct observations of HIV incidence by group in seven rounds of cohort data from four studies ("sites") conducted in Manicaland, Zimbabwe; Rakai, Uganda; Karonga, Malawi; and Kisesa, Tanzania. The IPM performed well, with the projections' credible intervals for the proportion of new infections per group overlapping the data's confidence intervals for all groups in all rounds of data. In terms of geographical distribution, the projections' credible intervals overlapped the confidence intervals for four out of seven rounds, which were used as proxies for administrative divisions in a country. We assessed model performance after internal training (within one site) and external training (between sites) by comparing mean posterior log-likelihoods and used the best model to estimate the distribution of HIV incidence in six countries (Gabon, Kenya, Malawi, Rwanda, Swaziland, and Zambia) in the region. We subsequently inferred the potential contribution of each group to transmission using a simple model that builds on the results from the IPM and makes further assumptions about sexual mixing patterns and transmission rates. In all countries except Swaziland, individuals in unions were the single group contributing to the largest proportion of new infections acquired (39%-77%), followed by never married women and men. Female sex workers accounted for a large proportion of new infections (5%-16%) compared to their population size. Individuals in unions were also the single largest contributor to the proportion of infections transmitted (35%-62%), followed by key populations and previously married men and women. Swaziland exhibited different incidence patterns, with never married men and women accounting for over 65% of new infections acquired and also contributing to a large proportion of infections transmitted (up to 56%). Between- and within-country variations indicated different incidence patterns in specific settings.
It is possible to reliably predict the distribution of new HIV infections acquired using data routinely available in many countries in the sub-Saharan African region with a single relatively simple mathematical model. This tool would complement more specific analyses to guide resource allocation, data collection, and programme planning.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Law enforcement officers (LEOs) come into frequent contact with people who inject drugs (PWID). Through service referrals, LEOs may facilitate PWID engagement in harm reduction, substance use ...treatment, and other health and supportive services. Little is known about PWID and LEO attitudes and concerns about service referrals, however. The objective of this mixed-methods study was to examine the alignment of service referral preferences and acceptability among PWID and LEOs in Tijuana, Mexico.
We assessed service referral preferences and perceived likelihood of participation in health and social services, integrating data from structured questionnaires with 280 PWID and 306 LEOs, contextualized by semi-structured interviews and focus groups with 15 PWID and 17 LEOs enrolled in two parallel longitudinal cohorts in Tijuana, Mexico.
Among potential service referral options, both PWID (78%) and LEOs (88%) most frequently cited assistance with drug- and alcohol-use disorders. Over half of PWID and LEOs supported including harm reduction services such as syringe service programs, overdose prevention, and HIV testing. The majority of PWID supported LEO referrals to programs that addressed basic structural needs (e.g. personal care 62%, food assistance 61%, housing assistance 58%). However, the proportion of LEOs (30-45%) who endorsed these service referrals was significantly lower (p < 0.01). Regarding referral acceptability, 71% of PWID reported they would be very likely or somewhat likely to make use of a referral compared to 94% of LEOs reporting that they thought PWID would always or sometimes utilize them. These results were echoed in the qualitative analysis, although practical barriers to referrals emerged, whereby PWID were less optimistic that they would utilize referrals compared to LEOs.
We identified strong support for LEO service referrals among both LEO and PWID respondents, with the highest preference for substance use treatment. LEO referral programs offer opportunities to deflect PWID contact with carceral systems while facilitating access to health and social services. However, appropriate investments and political will are needed to develop an evidence-based (integrated) service infrastructure.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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.
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.
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.
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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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
HIV incidence remains high among transgender women in Lima, Peru, most of whom report sex work. On the basis of a stakeholder analysis and health system capacity assessment, we designed a ...mathematical model to guide HIV programmatic planning among transgender women sex workers (TWSW) in Lima.
Using a deterministic compartmental model, we modelled HIV transmission among TWSW, their stable partners, and their clients to estimate the impact and cost-effectiveness of combinations of interventions compared with the standard of care on reducing HIV incidence over a 10-year period. We simulated HIV transmission accounting for differences in sexual positioning in anal intercourse and condom use by partner type and fitted the model to HIV surveillance data using Latin hypercube sampling. The interventions we considered were 15% relative increase in condom use with clients and 10% relative increase with stable partners; increase in antiretroviral treatment (ART) coverage at CD4 count lower than 500 cells per mm3 and greater than or equal to 500 cells per mm3; and 15% pre-exposure prophylaxis (PrEP) coverage using generic and branded formulations. We considered a basic scenario accounting for current limitations in the Peruvian HIV services and an enhanced scenario assuming achievement of the UNAIDS 90-90-90 targets and general improvements in HIV services. The 50 best fits according to log-likelihood were used to give the minimum and maximum values of intervention effect for each combination. We used disability-adjusted life-years (DALYs) to measure the negative health outcomes associated with HIV infection that could be averted through the interventions investigated and calculated incremental cost-effectiveness ratios to compare their cost-effectiveness.
Under the basic scenario, combining the four interventions of increasing condom use with clients and stable partners, extending ART to people with CD4 count greater than or equal to 500 cells per mm3, and 15% PrEP coverage with generic drugs would avert 47% (range 27–51) of new infections in TWSW, their clients, and their stable partners over 10 years, with an incremental cost-effectiveness ratio of US$509 per DALY averted. Under the enhanced scenario, this strategy would avert 61% (44–64) of new infections among this population with an incremental cost-effectiveness ratio of $1003 per DALY averted. Under both scenarios, implementation of this strategy approaches or surpasses the 50% incidence reduction goal and would represent a cost-effective use of country resources if generic PrEP drugs are used. The total cost of implementing this strategy under the enhanced scenario would be approximately $1·2 million per year over 10 years, corresponding to 10% of the current Global Fund's yearly contribution in Peru.
Investments in HIV services among TWSW in Lima would be cost-effective, even under stringent cost-effectiveness criteria when accounting for setting-specific resource constraints. Notable improvements in HIV testing rates, innovative interventions to increase condom use, and reduced PrEP costs will be key to achieving the 50% incidence reduction goal. Modelling studies incorporating stakeholders' perspectives and health system assessments can bring added value to HIV policy making.
National Institutes of Health.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Introduction
Among men who have sex with men (MSM) and transgender women (TW), stimulant use is high and has been associated with an increased risk of HIV infection, suicide and cardiovascular ...disease (CVD) mortality. We used epidemic modelling to investigate these intersecting health harms among MSM/TW in Lima, Peru and assess whether they could be mitigated by prioritizing HIV pre‐exposure prophylaxis (PrEP) and harm reduction interventions among MSM/TW who use stimulants.
Methods
We adapted a dynamic model of HIV transmission among MSM/TW in Lima to incorporate stimulant use and increased HIV risk, suicide and CVD mortality. Among 6% to 24% of MSM/TW using stimulants (mostly cocaine), we modelled an increased risk of unprotected anal sex (RR = 1.35 95%CI: 1.17 to 1.57) obtained from local data, and increased risk of suicide (SMR = 6.26 95%CI: 2.84 to 13.80) and CVD (SMR = 1.83 95%CI: 0.39 to 8.57) mortality associated with cocaine use based on a global systematic review. We estimated the proportion of health harms occurring among MSM/TW who use stimulants in the next year (01‐2020/01‐2021). We also investigated the 10‐year impact (01‐2020/01‐2030) of: (1) PrEP prioritization for stimulant‐using MSM/TW compared to random allocation, and (2) integrating PrEP with a theoretical intervention halving stimulant‐associated risk.
Results
MSM/TW in Lima will experience high HIV incidence, suicide mortality and CVD mortality (1.6/100 py, and 0.018/100 py, 0.13/100 py respectively) in 2020. Despite stimulant using MSM/TW comprising an estimated 9.5% (95%CI: 7.8 to 11.5) of all MSM/TW, in the next year, 11% 95%CI (i.e. 2.5% to 97.5% percentile) 10% to 13%) of new HIV infections, 39% (95%CI: 18% to 60%) of suicides and 15% (95%CI: 3% to 44%) of CVD deaths could occur among this group. Scaling up PrEP among all stimulant using MSM/TW could prevent 19% (95%CI: 11% to 31%) more HIV infections over 10 years compared to random allocation. Integrating PrEP and an intervention to halve stimulant‐associated risks could reduce new HIV infections by 20% (95%CI: 10% to 37%), suicide deaths by 14% (95%CI: 5% to 27%) and CVD deaths by 3% (95%CI: 0% to 16%) over a decade.
Conclusions
MSM/TW who use stimulants experience a disproportionate burden of health harms. Prioritizing PrEP based on stimulant use, in addition to sexual behaviour/gender identity criteria, could increase its impact. Integrated substance use, harm reduction, mental health and HIV care among MSM/TW is needed.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
International guidelines for interventions and medical care promote health by enabling populations to benefit from the best scientific evidence and accumulated experience of the global community. ...However, setting guidelines is difficult, especially when the best clinical practice has to be balanced with practical constraints and concern for overall population health outcomes. The 2013 consolidated guidelines for the use of antiretro-virals to treat HIV, promulgated by the World Health Organization (WHO), replace several distinct guideline documents about the provision of antiretrovirals in different circumstances 1. In providing such guidance, the consequences of decisions must simultaneously be considered in many dimensions (morbidity, mortality, new infections, resistance, resource needs) and over a range of timescales, whilst also weighing the strength of various forms of evidence and accounting for the attendant uncertainties. These questions lend themselves to mathematical modeling and economic evaluation as a means to synthesize data in a transparent and precise way and to anticipate the implications of competing approaches for population health 2.
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