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  1. Zelenev A, Li J, Mazhnaya A, Basu S, Altice FL
    Lancet Infect Dis, 2018 02;18(2):215-224.
    PMID: 29153265 DOI: 10.1016/S1473-3099(17)30676-X
    BACKGROUND: Chronic infections with hepatitis C virus (HCV) and HIV are highly prevalent in the USA and concentrated in people who inject drugs. Treatment as prevention with highly effective new direct-acting antivirals is a prospective HCV elimination strategy. We used network-based modelling to analyse the effect of this strategy in HCV-infected people who inject drugs in a US city.

    METHODS: Five graph models were fit using data from 1574 people who inject drugs in Hartford, CT, USA. We used a degree-corrected stochastic block model, based on goodness-of-fit, to model networks of injection drug users. We simulated transmission of HCV and HIV through this network with varying levels of HCV treatment coverage (0%, 3%, 6%, 12%, or 24%) and varying baseline HCV prevalence in people who inject drugs (30%, 60%, 75%, or 85%). We compared the effectiveness of seven treatment-as-prevention strategies on reducing HCV prevalence over 10 years and 20 years versus no treatment. The strategies consisted of treatment assigned to either a randomly chosen individual who injects drugs or to an individual with the highest number of injection partners. Additional strategies explored the effects of treating either none, half, or all of the injection partners of the selected individual, as well as a strategy based on respondent-driven recruitment into treatment.

    FINDINGS: Our model estimates show that at the highest baseline HCV prevalence in people who inject drugs (85%), expansion of treatment coverage does not substantially reduce HCV prevalence for any treatment-as-prevention strategy. However, when baseline HCV prevalence is 60% or lower, treating more than 120 (12%) individuals per 1000 people who inject drugs per year would probably eliminate HCV within 10 years. On average, assigning treatment randomly to individuals who inject drugs is better than targeting individuals with the most injection partners. Treatment-as-prevention strategies that treat additional network members are among the best performing strategies and can enhance less effective strategies that target the degree (ie, the highest number of injection partners) within the network.

    INTERPRETATION: Successful HCV treatment as prevention should incorporate the baseline HCV prevalence and will achieve the greatest benefit when coverage is sufficiently expanded.

    FUNDING: National Institute on Drug Abuse.

  2. Zelenev A, Long E, Bazazi AR, Kamarulzaman A, Altice FL
    PMID: 27639995 DOI: 10.1016/j.drugpo.2016.08.008
    BACKGROUND: HIV is primarily concentrated among people who inject drugs (PWID) in Malaysia, where currently HIV prevention and treatment coverage is inadequate. To improve the targeting of interventions, we examined HIV clustering and the role that social networks and geographical distance play in influencing HIV transmission among PWID.

    METHODS: Data were derived from a respondent-driven survey sample (RDS) collected during 2010 of 460 PWID in greater Kuala Lumpur. Analysis focused on socio-demographic, clinical, behavioural, and network information. Spatial probit models were developed based on a distinction between the influence of peers (individuals nominated through a recruitment network) and neighbours (residing a close distance to the individual). The models were expanded to account for the potential influence of the network formation.

    RESULTS: Recruitment patterns of HIV-infected PWID clustered both spatially and across the recruitment networks. In addition, HIV-infected PWID were more likely to have peers and neighbours who inject with clean needles were HIV-infected and lived nearby (<5km), more likely to have been previously incarcerated, less likely to use clean needles (26.8% vs 53.0% of the reported injections, p<0.01), and have fewer recent injection partners (2.4 vs 5.4, p<0.01). The association between the HIV status of peers and neighbours remained significantly correlated even after controlling for unobserved variation related to network formation and sero-sorting.

    CONCLUSION: The relationship between HIV status across networks and space in Kuala Lumpur underscores the importance of these factors for surveillance and prevention strategies, and this needs to be more closely integrated. RDS can be applied to identify injection network structures, and this provides an important mechanism for improving public health surveillance, accessing high-risk populations, and implementing risk-reduction interventions to slow HIV transmission.

  3. Tan J, Altice FL, Madden LM, Zelenev A
    Lancet HIV, 2020 02;7(2):e121-e128.
    PMID: 31879250 DOI: 10.1016/S2352-3018(19)30373-X
    BACKGROUND: As HIV incidence and mortality continue to increase in eastern Europe and central Asia, particularly among people who inject drugs (PWID), it is crucial to effectively scale-up opioid agonist therapy (OAT), such as methadone or buprenorphine maintenance therapy, to optimise HIV outcomes. With low OAT coverage among PWID, we did an optimisation assessment using current OAT procurement and allocation, then modelled the effect of increased OAT scale-up on HIV incidence and mortality for 23 administrative regions of Ukraine.

    METHODS: We developed a linear optimisation model to estimate efficiency gains that could be achieved based on current procurement of OAT. We also developed a dynamic, compartmental population model of HIV transmission that included both injection and sexual risk to estimate the effect of OAT scale-up on HIV infections and mortality over a 10-year horizon. The compartmental population model was calibrated to HIV prevalence and incidence among PWID for 23 administrative regions of Ukraine. Sources for regional data included the SyrEx database, the Integrated Biological and Behavioral Survey, the Ukrainian Center for Socially Dangerous Disease Control of the Ministry of Health of Ukraine, the Public Health Center of the Ministry of Health of Ukraine, and the Ukrainian Census.

    FINDINGS: Under a status-quo scenario (OAT coverage of 2·7% among PWID), the number of new HIV infections among PWID in Ukraine over the next 10 years was projected to increase to 58 820 (95% CI 47 968-65 535), with striking regional differences. With optimum allocation of OAT without additional increases in procurement, OAT coverage could increase from 2·7% to 3·3% by increasing OAT doses to ensure higher retention levels. OAT scale-up to 10% and 20% over 10 years would, respectively, prevent 4368 (95% CI 3134-5243) and 10 864 (7787-13 038) new HIV infections and reduce deaths by 7096 (95% CI 5078-9160) and 17 863 (12 828-23 062), relative to the status quo. OAT expansion to 20% in five regions of Ukraine with the highest HIV burden would account for 56% of new HIV infections and 49% of deaths prevented over 10 years.

    INTERPRETATION: To optimise HIV prevention and treatment goals in Ukraine, OAT must be substantially scaled up in all regions. Increased medication procurement is needed, combined with optimisation of OAT dosing. Restricting OAT scale-up to some regions of Ukraine could benefit many PWID, but the regions most affected are not necessarily those with the highest HIV burden.

    FUNDING: National Institute on Drug Abuse.

  4. Zelenev A, Li J, Shea P, Hecht R, Altice FL
    Clin Infect Dis, 2020 Feb 15.
    PMID: 32060534 DOI: 10.1093/cid/ciaa142
    BACKGROUND: HCV treatment as prevention (TasP) strategies can contribute to HCV micro-elimination, yet complimentary interventions like opioid agonist therapies (OAT) and syringe services programs (SSP) may improve the prevention impact. This modeling study estimates the impact of scaling up the combination of OAT and SSP with HCV TasP in a network of people who inject drugs (PWID) in the U.S.

    METHODS: Using empirical data from Hartford, Connecticut, we deployed a stochastic block model to simulate an injection network of 1,574 PWID. We used a susceptible-infected model for HCV and HIV to evaluate the effectiveness of several HCV TasP strategies, including in combination with OAT and SSP scale-up, over 20 years.

    RESULTS: At the highest HCV prevalence (75%), when OAT coverage is increased from 10% to 40%, combined with HCV treatment of 10 % per year, the time to achieve micro-elimination reduces from 18.4 to 11.6 years. At the current HCV prevalence (60%), HCV TasP strategies as low as 10% coverage per year may achieve HCV micro-elimination within 10-years, with minimal impact from additional OAT scale-up.  Strategies based on mass initial HCV treatment (50 per 100 PWID the first year followed by 5 per 100 PWID thereafter) were most effective in settings with HCV prevalence of 60% or lower.

    CONCLUSIONS: Scale up of HCV TasP is the most effective strategy for micro-elimination of HCV. However, OAT scale-up may be synergistic toward achieving micro-elimination goals when HCV prevalence exceeds 60% and when HCV treatment coverage is 10 per 100 PWID per year or lower.

  5. Meyer JP, Zelenev A, Wickersham JA, Williams CT, Teixeira PA, Altice FL
    Am J Public Health, 2014 Mar;104(3):434-41.
    PMID: 24432878 DOI: 10.2105/AJPH.2013.301553
    We assessed gender differences in longitudinal HIV treatment outcomes among HIV-infected jail detainees transitioning to the community.
  6. Morano JP, Zelenev A, Walton MR, Bruce RD, Altice FL
    Am J Public Health, 2014 Aug;104(8):1508-15.
    PMID: 24922157 DOI: 10.2105/AJPH.2014.301897
    OBJECTIVES: We evaluated the efficacy of a mobile medical clinic (MMC) screening program for detecting latent tuberculosis infection (LTBI) and active tuberculosis.
    METHODS: A LTBI screening program in a MMC in New Haven, Connecticut, used medical surveys to examine risk factors and tuberculin skin test (TST) screening eligibility. We assessed clinically relevant correlates of total (prevalent; n = 4650) and newly diagnosed (incident; n = 4159) LTBI from 2003 to 2011.
    RESULTS: Among 8322 individuals, 4159 (55.6%) met TST screening eligibility criteria, of which 1325 (31.9%) had TST assessed. Similar to LTBI prevalence (16.8%; 779 of 4650), newly diagnosed LTBI (25.6%; 339 of 1325) was independently correlated with being foreign-born (adjusted odds ratio [AOR] = 8.49; 95% confidence interval [CI] = 5.54, 13.02), Hispanic (AOR = 3.12; 95% CI = 1.88, 5.20), Black (AOR = 2.16; 95% CI = 1.31, 3.55), employed (AOR = 1.61; 95% CI = 1.14, 2.28), and of increased age (AOR = 1.04; 95% CI = 1.02, 1.05). Unstable housing (AOR = 4.95; 95% CI = 3.43, 7.14) and marijuana use (AOR = 1.57; 95% CI = 1.05, 2.37) were significantly correlated with incident LTBI, and being male, heroin use, interpersonal violence, employment, not having health insurance, and not completing high school were significantly correlated with prevalent LTBI.
    CONCLUSIONS: Screening for TST in MMCs successfully identifies high-risk foreign-born, Hispanic, working, and uninsured populations and innovatively identifies LTBI in urban settings.
    Study site: Mobile clinic, New Haven, Connecticut, United States
  7. Bazazi AR, Crawford F, Zelenev A, Heimer R, Kamarulzaman A, Altice FL
    AIDS Behav, 2015 Dec;19(12):2347-57.
    PMID: 26358544 DOI: 10.1007/s10461-015-1191-y
    The HIV epidemic in Malaysia is concentrated among people who inject drugs (PWID). Accurate estimates of HIV prevalence are critical for developing appropriate treatment and prevention interventions for PWID in Malaysia. In 2010, 461 PWID were recruited using respondent-driven sampling in Greater Kuala Lumpur, Malaysia. Participants completed rapid HIV testing and behavioral assessments. Estimates of HIV prevalence were computed for each of the three recruitment sites and the overall sample. HIV prevalence was 15.8 % (95 % CI 12.5-19.2 %) overall but varied widely by location: 37.0 % (28.6-45.4 %) in Kampung Baru, 10.3 % (5.0-15.6 %) in Kajang, and 6.3 % (3.0-9.5 %) in Shah Alam. Recruitment extended to locations far from initial interview sites but was concentrated around discrete geographic regions. We document the high prevalence of HIV among PWID in Greater Kuala Lumpur. Sustained support for community surveillance and HIV prevention interventions is needed to stem the HIV epidemic among PWID in Malaysia.
  8. Bazazi AR, Zelenev A, Fu JJ, Yee I, Kamarulzaman A, Altice FL
    PMID: 25532449 DOI: 10.1016/j.drugpo.2014.11.010
    Overdose is the leading cause of death among opioid users, but no data are available on overdose among people who inject drugs in Malaysia. We present the first estimates of the prevalence and correlates of recent non-fatal overdose among people who inject drugs in Malaysia.
  9. Iakunchykova O, Meteliuk A, Zelenev A, Mazhnaya A, Tracy M, Altice FL
    PMID: 29655101 DOI: 10.1016/j.drugpo.2018.03.022
    BACKGROUND: Among the estimated 340,000 people who inject drugs (PWID) in Ukraine, HCV prevalence is approximately 70%. As HCV treatment availability increases, an assessment of the HCV treatment cascade is needed to guide HCV prevention and treatment strategies.

    METHODS: Opioid dependent PWID were interviewed and tested for HIV and HCV in five Ukrainian cities from January 2014 to March 2015. Logistic regression was used to examine the independent correlates of two cascade steps: a) anti-HCV positive status awareness; b) chronic HCV confirmation; and of c) annual HCV testing for PWID.

    RESULTS: Among 1613 PWID, 1002 (62.1%) had anti-HCV positive test result, of which 568 (56.7%) were aware of it before the study and 346 (34.5%) reported previous confirmatory testing for chronic HCV. Independent correlates of being aware they had anti-HCV positivity included: current [AOR: 3.08; 95%CI: 2.16-4.40] or prior [AOR: 1.85; 95%CI: 1.27-2.68] opioid agonistic treatment (OAT) experience, relative to no prior OAT, living in Lviv [AOR: 0.50; 95%CI: 0.31-0.81] or Odesa [AOR: 2.73; 95%CI: 1.51-4.93] relative to Kyiv and being aware of having HIV [AOR: 4.10; 95%CI: 2.99-5.62]. Independent correlates of confirming HCV infection among those who were aware of their anti-HCV positive status included: current OAT [AOR: 2.00; 95%CI: 1.24-3.23], relative to prior OAT, the middle income category [AOR: 1.74, 95%CI: 1.15-2.63], relative to the lowest, and receiving ART [AOR: 4.54; 95%CI: 2.85-7.23]. Among 1613 PWID, 918 (56.9%) were either HCV negative or not aware of their HCV positive status, of which 198 (21.6%) reported recent anti-HCV test (during last 12 month). Recent anti-HCV test in this group was associated with current [AOR: 7.17; 95%CI: 4.63-11.13] or prior [AOR: 2.24; 95%CI: 1.32-3.81] OAT experience, relative to no prior OAT.

    CONCLUSION: Encouraging PWID to participate in OAT may be an effective strategy to diagnose and link PWID who are HCV positive to care. Among HIV negative participants, regular HCV testing may be ensured by participation in OAT. More studies are needed to assess HCV treatment utilization among PWID in Ukraine and OAT as a possible way to retain them in treatment.

  10. Marcus R, Makarenko I, Mazhnaya A, Zelenev A, Polonsky M, Madden L, et al.
    Drug Alcohol Depend, 2017 10 01;179:213-219.
    PMID: 28806638 DOI: 10.1016/j.drugalcdep.2017.07.010
    BACKGROUND: Scaling up HIV prevention for people who inject drugs (PWID) using opioid agonist therapies (OAT) in Ukraine has been restricted by individual and structural factors. Extended-release naltrexone (XR-NTX), however, provides new opportunities for treating opioid use disorders (OUDs) in this region, where both HIV incidence and mortality continue to increase.

    METHODS: Survey results from 1613 randomly selected PWID from 5 regions in Ukraine who were currently, previously or never on OAT were analyzed for their preference of pharmacological therapies for treating OUDs. For those preferring XR-NTX, independent correlates of their willingness to initiate XR-NTX were examined.

    RESULTS: Among the 1613 PWID, 449 (27.8%) were interested in initiating XR-NTX. Independent correlates associated with interest in XR-NTX included: being from Mykolaiv (AOR=3.7, 95% CI=2.3-6.1) or Dnipro (AOR=1.8, 95% CI=1.1-2.9); never having been on OAT (AOR=3.4, 95% CI=2.1-5.4); shorter-term injectors (AOR=0.9, 95% CI 0.9-0.98); and inversely for both positive (AOR=0.8, CI=0.8-0.9), and negative attitudes toward OAT (AOR=1.3, CI=1.2-1.4), respectively.

    CONCLUSIONS: In the context of Eastern Europe and Central Asia where HIV is concentrated in PWID and where HIV prevention with OAT is under-scaled, new options for treating OUDs are urgently needed.

    FINDINGS: here suggest that XR-NTX could become an option for addiction treatment and HIV prevention especially for PWID who have shorter duration of injection and who harbor negative attitudes to OAT. Decision aids that inform patient preferences with accurate information about the various treatment options are likely to guide patients toward better, patient-centered treatments and improve treatment entry and retention.

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