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This study estimated latent classes (ie, unobserved subgroups in a population) of people who use drugs in Vancouver, Canada, and examined how these classes relate to phylogenetic clustering of hepatitis C virus (HCV) infection. HCV antibody-positive people who use drugs from two cohorts in Vancouver, Canada (1996-2012), with a Core-E2 sequence were included. Time-stamped phylogenetic trees were inferred, and phylogenetic clustering was determined by time to most common recent ancestor. Latent classes were estimated, and the association with the phylogenetic clustering outcome was assessed using an inclusive classify/analyse approach. Among 699 HCV RNA-positive participants (26% female, 24% HIV+), recent drug use included injecting cocaine (80%), injecting heroin (70%), injecting cocaine/heroin (ie, speedball, 38%) and crack cocaine smoking (28%). Latent class analysis identified four distinct subgroups of drug use typologies: (i) cocaine injecting, (ii) opioid and cocaine injecting, (iii) crack cocaine smoking and (iv) heroin injecting and currently receiving opioid substitution therapy. After adjusting for age and HIV infection, compared to the group defined by heroin injecting and currently receiving opioid substitution therapy, the odds of phylogenetic cluster membership was greater in the cocaine injecting group (adjusted OR [aOR]: 3.06; 95% CI: 1.73, 5.42) and lower in the crack cocaine smoking group (aOR: 0.06; 95% CI: 0.01, 0.48). Combining latent class and phylogenetic clustering analyses provides novel insights into the complex dynamics of HCV transmission. Incorporating differing risk profiles associated with drug use may provide opportunities to further optimize and target HCV treatment and prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Studies of HCV reinfection following direct-acting antiviral (DAA) therapy among PWID have been limited by short follow-up and small case numbers. This study evaluated the incidence of HCV reinfection following successful DAA therapy among people attending an inner-city community health centre in Victoria, Canada., Methods: In this observational study, participants treated with DAA therapy between November 2014 and December 31, 2019 were included. Retrospective chart review was performed to assess demographics, recent injecting drug use at treatment initiation (previous six months), opioid agonist treatment (OAT), and HIV. Endpoints included sustained virologic response (SVR), HCV reinfection, and mortality., Results: Of 482 participants initiating DAA treatment, 30% were female, 46% were receiving OAT, 49% had recent injection drug use, 15% had HIV/HCV coinfection, and 22% had cirrhosis. Treatment completion was 97% (468/482; 12 discontinued therapy, and 2 died during treatment). SVR was 87% (418/482). Outcomes among those who completed treatment but did not achieve SVR (n=53), included loss to follow-up (n=11), HCV RNA for SVR testing not completed (n=18), viral relapse (n=6), reinfection (n=5) and viral recurrence (n=5, unable to distinguish viral relapse from reinfection), and death (n=7). The rate of HCV reinfection was 3.6/100 person-years (95% confidence interval [CI] 2.4-5.5; 22 cases; 602 person-years follow-up). Factors associated with an increased risk of HCV reinfection included recent injection drug use (adjusted relative risk [aRR] 8.55, 95% CI 1.98-36.96) and HIV co-infection (aRR 2.35, 95% CI 1.01-5.44). Fifty-five people died (overdose, n=19) during (n=2) or following (n=53) therapy (7.4/100 person-years; 95% CI 5.6-9.6)., Conclusion: This study demonstrates ongoing reinfection among a marginalized population at an inner-city community health centre, with higher rates among those with HIV and recent injecting drug use. The rates of reinfection and mortality highlight the importance of integrating HCV care with strategies to address drug-related harms., Competing Interests: Declarations of Interest J. G. reports grants and personal fees from AbbVie, Camurus, Cepheid, Gilead Sciences, Hologic, Indivior, and Merck. C.F. reports grants from Kirby Institute, Abbvie, Gilead, Merck, and ViiV., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Frequent injecting increases hepatitis C (HCV) acquisition risk among people who inject drugs (PWID). However, few studies have examined how temporal fluctuations in injecting frequency may effect HCV infection risk. Thus, this study examined HCV incidence according to injecting frequency trajectories followed by PWID over one year in Montréal, Canada., Methods: At three-month intervals from March 2011 to June 2016, HCV-uninfected PWID (never infected or cleared infection) enrolled in the Hepatitis Cohort (HEPCO) completed interviewer-administered questionnaires and HCV testing. At each visit, participants reported the number of injecting days (0-30 days) for each of the past three months. In previous work, using group-based trajectory modeling, we identified five injecting frequency trajectories followed by participants over one year (months 1-12 of follow-up), including sporadic, infrequent, increasing, decreasing, and frequent injecting. In this study, we estimated group-specific HCV incidence (months 1-63 of follow-up) using posterior probabilities to assign participants to their most likely trajectory group., Results: Of 386 participants (mean age=40, 82% male, 48% never HCV-infected), 72 acquired HCV during 893 person-years of follow-up. HCV incidence for the whole study sample was 8.1 per 100 person-years (95%CI=6.4-10.1). Trajectory group-specific HCV incidences were highest for those injecting drugs with decreasing (23.9, 14.4-37.5) or increasing frequency (16.0, 10.1-24.3), intermediate for those injecting at consistently high frequency (10.2, 5.4-17.8), and lowest for those injecting infrequently (3.9, 2.2-6.5) or sporadically (4.3, 2.2-7.6)., Conclusion: Results suggest that PWID at highest HCV risk are those injecting at high frequency, either transitorily (increasing, decreasing injecting) or consistently (frequent injecting). This study highlights changes in injecting frequency as a potentially important dimension to consider among the factors leading to HCV acquisition. Clinical and public health interventions tailored to PWID with different injecting frequency profiles may contribute to HCV prevention., Competing Interests: Declarations of Interest No author has commercial relationships that might pose a conflict of interest in connection with this work. MPS is supported through a FRQS researcher salary award. AAA is supported through postdoctoral fellowships from CIHR, FRQS and the Canadian Network on Hepatitis C (CanHepC). NM is supported through FRQS and CanHepC doctoral scholarships. DJA is supported through a FRQS clinical researcher salary award. JG is supported through a career development fellowship from the National Health and Medical Research Council (NHMRC). JG is also a consultant/advisor and has received research grants from AbbVie, Bristol-Myers Squibb, Gilead and Merck. JB holds a Canada Research Chair in Addiction Medicine. JB is also a consultant/advisor and has received research grants from Gilead and AbbVie., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background & Aims: Shortened duration therapy for acute and recent HCV infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens; however, large randomised studies are lacking., Methods: REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early., Results: The primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n = 93), standard arm (n = 95). Ninety-seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4-89.0) in the short arm and 86/95, 90.5% (95% CI 82.7-95.6) in the standard arm. The difference between the arms was -8.8 (95% CI -18.6 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss to follow-up), SVR12 was 76/85, 89.4% (95% CI 80.8-95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0-99.7; difference -8.3%, p = 0.025)., Conclusions: In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy., Lay Summary: In this randomised trial, 188 people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. CLINICALTRIALS., Gov Identifier: NCT02625909., Competing Interests: Conflict of interest GVM: grants from Gilead Sciences and AbbVie Inc, outside the submitted work; SB: grants from Gilead Sciences, outside the submitted work; personal fees for Advisory Boards and lectures/presentations from Gilead Sciences, outside the submitted work; MvDW: grants and personal fees from AbbVie, grants and personal fees from Gilead, grants and personal fees from Johnson & Johnson, grants and personal fees from MSD, grants and personal fees from ViiV, outside the submitted work; JR: personal fees from Gilead Sciences, Janssen, Merck, Theratechnologies and ViiV, outside the submitted work; JF: grants and personal fees from Gilead Sciences, grants and personal fees from AbbVie, personal fees from GSK, personal fees from Roche, grants from Janssen, grants from Eiger, grants and personal fees from Enanta, personal fees from Arubutus, outside the submitted work; AR: Advisory boards: MSD, Gilead Sciences, Travel grants: Gilead Sciences, Pfizer, AbbVie; Research support: Investigator initiated trial grant from Gilead Sciences. All remuneration went to his home institution and not to Dr. Rauch personally; CT: Gilead Advisory board (Remdesivir) 2020; MSD Advisory board (HCV) 2018; educational grants from Gilead and AbbVie (Annual Preceptorship on HCV in PWID), outside the submitted work; JB: grants from NIH, during the conduct of the study; personal fees from AbbVie, grants and personal fees from Gilead, outside the submitted work; AK: grants from PCORI, grants from NIH/NIAID, grants from NIH/NIA, grants from UpToDate, Inc., personal fees from Biomarin, Inc., personal fees for lectures/presentations: CME companies, Clinical Care Options companies, Mentor Planning and Practice Point, personal fees from DKBMed for communications, personal fees for academic work from Geisinger Health Systems and St. Luke’s/Roosevelt, personal fees from Ken Krayesek Law Offices, personal fees from Duke University, outside the submitted work; MH: grants from Gilead Sciences, grants from AbbVie, outside the submitted work; EG: personal fees from Gilead Scientific Advisory Board, personal fees from AbbVie Scientific Advisory Board, personal fees from Janssen Scientific Advisory Board, outside the submitted work; MN: grants, personal fees and non-financial support from AbbVie, grants, personal fees and non-financial support from MSD, grants, personal fees and non-financial support from BMS, grants, personal fees and non-financial support from Gilead Sciences, payment or honoraria: Gilead, AbbVie, BMS and MSD, travel support: Gilead, AbbVie, BMS and MSD, personal fees from MBS DMSB or equivalent, outside the submitted work; PI: grants and personal fees from Gilead Sciences, personal fees from AbbVie, personal fees from ViiV, outside the submitted work; JG: grants and personal fees from AbbVie, grants and personal fees from Gilead Sciences, grants and personal fees from Merck, grants and personal fees from Cepheid, grants from Hologic, grants from Indivior, payment or honoraria: AbbVie, Gilead Sciences and Cepheid, travel support: AbbVie, Gilead Sciences and Cepheid, receipt of testing equipment and cartridges from Cepheid, receipt of testing reagents from Hologic, outside the submitted work; KP: grants from Gilead sciences Australia and ViiV Healthcare Australia, outside the submitted work; GD: grants, personal fees and non-financial support from Gilead Sciences, AbbVie and Merck, grants from Bristol-Myers Squibb, outside the submitted work; DS, MM, TA and PM: nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021. Published by Elsevier B.V.)

Importance: Achievement of the World Health Organization (WHO) target of eliminating hepatitis C virus (HCV) by 2030 will require an increase in key services, including harm reduction, HCV screening, and HCV treatment initiatives in member countries. These data are not available for Canada but are important for informing a national HCV elimination strategy., Objective: To use a decision analytical model to explore the association of different treatment strategies with HCV epidemiology and HCV-associated mortality in Canada and to assess the levels of service increase needed to meet the WHO elimination targets by 2030., Design, Setting, and Participants: Study participants in this decision analytical model included individuals with hepatitis C virus infection in Canada. Five HCV treatment scenarios (optimistic, very aggressive, aggressive, gradual decrease, and rapid decrease) were applied using a previously validated Markov-type mathematical model. The optimistic and very aggressive treatment scenarios modeled a sustained annual treatment of 10 200 persons and 14 000 persons, respectively, from 2018 to 2030. The aggressive, gradual decrease, and rapid decrease scenarios assessed decreases in treatment uptake from 14 000 persons to 10 000 persons per year, 12 000 persons to 8500 persons per year, and 12 000 persons to 4500 persons per year, respectively, between 2018 and 2030., Main Outcomes and Measures: Hepatitis C virus prevalence and HCV-associated health outcomes were assessed for each of the 5 treatment scenarios with the goal of identifying strategies to achieve HCV elimination by 2030., Results: An estimated mean 180 142 persons (95% CI, 122 786-196 862 persons) in Canada had chronic HCV infection at the end of 2017. The optimistic and gradual decrease scenarios estimated a decrease in HCV prevalence from 180 142 persons to 37 246 persons and 37 721 persons, respectively, by 2030. Relative to 2015, this decrease in HCV prevalence was associated with 74%, 69%, and 69% reductions in the prevalence of decompensated cirrhosis, hepatocellular carcinoma, and liver-associated mortality, respectively, leading to HCV elimination by 2030. More aggressive treatment uptake (very aggressive scenario) could result in goal achievement up to 3 years earlier than 2030, although a rapid decrease in the initiation of treatment (rapid decrease scenario) would preclude Canada from reaching the HCV elimination goal by 2030., Conclusions and Relevance: The study findings suggest that Canada could meet the WHO goals for HCV elimination by 2030 by sustaining the current national HCV treatment rate during the next decade. This target will not be achieved if treatment uptake is allowed to decrease rapidly.

Objectives. To determine the number of people who inject drugs (PWID) in Canada and the annual coverage of opioid agonist treatment (OAT) and needle-and-syringe provision for PWID. Methods. We estimated the number of PWID in 11 of 13 Canadian provinces and territories in 2011 by using indirect multiplier methods based on provincial and territorial methadone recipient totals and proportion of surveyed PWID receiving methadone. We modeled annual increases for 2011 to 2016 on Quebec and British Columbia longitudinal data. We calculated needle-and-syringe coverage (World Health Organization [WHO] recommendation: ≥ 200 per PWID) and OAT coverage (WHO recommendation: ≥ 40 per 100 PWID) per province and territory annually. Results. An estimated 130 000 individuals in Canada (0.55%) injected drugs in 2011, increasing to 171 900 individuals (0.70%) in 2016. Needle-and-syringe coverage increased from 193 to 291 per PWID, and OAT coverage increased from 55 to 66 per 100 PWID over the study period. Conclusions. While the number of PWID increased between 2011 and 2016, OAT coverage remained high, and needle-and-syringe coverage generally improved over time. Public Health Implications. These data will inform public health surveillance, service planning, and resource allocation, and assist monitoring of treatment and harm-reduction coverage outcomes.

The aim of this analysis was to evaluate perceived barriers related to HCV testing, management and treatment among physicians practicing in clinics offering opioid agonist treatment (OAT). C-SCOPE was a study consisting of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe and the United States between April and May 2017. A 5-point Likert scale (1 = not a barrier, 3 = moderate barrier, 5 = extreme barrier) was used to measure responses to perceived barriers for HCV testing, evaluation and treatment across the domains of the health system, clinic and patient. Among the 203 physicians enrolled (40% USA, 45% Europe, 14% Australia/Canada), 21% were addiction medicine specialists, 29% psychiatrists and 69% were metro/urban. OAT physicians in this study reported poor access to on-site venepuncture (35%), point-of-care HCV testing (16%), and noninvasive liver disease assessment (25%). Only 30% of OAT physicians reported personally treating HCV infection. Major perceived health system barriers to HCV management included the lack of funding for noninvasive liver disease testing, long wait times to see an HCV specialist, lack of funding for new HCV therapies, and reimbursement restrictions based on drug/alcohol use. Major perceived clinic barriers included the lack of peer support programmes and/or HCV case managers to facilitate linkage to care, the need to refer people off-site for noninvasive liver disease staging, the lack of support for on-site phlebotomy and the lack of on-site delivery of HCV therapy. This study highlights several important modifiable barriers to enhance HCV testing, evaluation and treatment among PWID attending OAT clinics., (© 2019 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.)

Background and Aims: For most people who inject drugs (PWID), drug injecting follows a dynamic process characterized by transitions in and out of injecting. The objective of this investigation was to examine injecting cessation episodes of 1-3-month duration as predictors of hepatitis C virus (HCV) acquisition., Design: Cohort study., Setting: Montréal, Canada., Participants: A total of 372 HCV-uninfected (HCV RNA-negative, HCV antibody-positive or -negative) PWID (mean age = 39.3 years, 82% male, 45% HCV antibody-positive) enrolled between March 2011 and June 2016., Measurements: At 3-month intervals, participants completed an interviewer-administered questionnaire and were tested for HCV particles (HCV RNA). At each visit, participants indicated whether they injected in each of the past 3 months (defined as three consecutive 30-day periods). Injecting cessation patterns were evaluated on a categorical scale: persistent injecting (no injecting cessation in the past 3 months), sporadic injecting cessation (injecting cessation in 1 of 3 or 2 of 3 months) and short injecting cessation (injecting cessation in 3 of 3 months). Their association with HCV infection risk was examined using Cox regression analyses with time-dependent covariates, including age, gender, incarceration, opioid agonist treatment and other addiction treatments., Findings: At baseline, 61, 26 and 13% of participants reported persistent injecting, sporadic injecting cessation and short injecting cessation, respectively. HCV incidence was 7.5 per 100 person-years [95% confidence interval (CI) = 5.9-9.5; 916 person-years of follow-up]. In adjusted Cox models, sporadic injecting cessation and short injecting cessation were associated with lower risks of incident HCV infection compared to persistent injecting (adjusted hazard ratios = 0.56, 95% CI = 0.30-1.04 and 0.24, 95% CI = 0.09-0.61), respectively., Conclusion: Short and sporadic injecting cessation episodes were common among a cohort of people who inject drugs in Montréal, Canada. Injecting cessation episodes appear to be protective against hepatitis C virus acquisition, particularly when maintained for at least 3 months., (© 2019 Society for the Study of Addiction.)

It is estimated that 6.1 million people with recent injecting drug use (PWID) are living with hepatitis C virus (HCV). Although HCV-related morbidity and mortality among PWID continues to increase, the advent of direct acting antiviral (DAA) HCV regimens with cure rates >95% provides an opportunity to reverse the rising burden of disease. Additionally, given evidence that opioid substitution therapy and high-coverage needle and syringe programs can reduce HCV incidence by up to 80%, there is an opportunity to reduce HCV transmission with increased coverage of harm reduction services. However, there are significant patient, provider, health system, structural, and societal barriers that impede access to HCV prevention and care for PWID. The International Network on Hepatitis in Substance Users (INHSU), in collaboration with the Australasian Society for HIV, Viral Hepatitis, Sexual Health Medicine (ASHM), Harm Reduction International, the Canadian Network on Hepatitis C, Canadian Research Initiative in Substance Misuse, the National Viral Hepatitis Roundtable, Médecins du Monde and CATIE, held a roundtable discussion prior to the Harm Reduction Conference in Montreal, Canada on 13th May 2017 to discuss how to improve HCV prevention and care for PWID. Over 100 international researchers, practitioners, policy makers, advocates, and affected community members came together to discuss shared priorities for action, develop actionable next steps and to create partnerships to enable application of priorities. This paper highlights the key priority areas identified by participants including: enhancing global coverage of harm reduction services; addressing punitive drug policies; ensuring access to affordable HCV diagnostics and treatment; improving the evidence-base for HCV prevention, testing, linkage to care and treatment; implementing integrated HCV programs; advancing peer-based models of HCV care; and tackling social determinants of health inequalities for PWID. This paper also highlights the recommended actions for each priority identified by the participants from this roundtable., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: This study evaluated competency related to HCV testing, management and treatment among physicians practicing in clinics offering opioid agonist treatment (OAT)., Methods: C-SCOPE is a study consisting of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe and USA between April-May 2017. A 7-point scale was used to measure < average competence (score >4 of 7) related to HCV testing, management and treatment., Results: Among 203 physicians (40% USA, 45% Europe, 14% Australia/Canada) 21% were addiction medicine specialists, 29% psychiatrists, and 70% were metro/urban [mean PWID managed, 51; years of experience, 11]. The majority perceived HCV testing (82%) and treatment (85%) among PWID as important. The minority reported < average competence with respect to regular screening (12%) and interpretation of HCV test results (14%), while greater proportions reported < average competence in advising patients about new HCV therapies (28%), knowledge of new treatments (37%), and treatment/management of HCV (40%). In adjusted analysis, factors independently associated with < average self-reported competency related to the ability to treat HCV and manage side effects included fewer years in medical practice, fewer numbers of patients treated for HCV infection in the past six months, not having obtained information on screening, diagnosing or treatment of HCV, not having attended any training on HCV in the past year, and not having read or consulted AASLD/IDSA, EASL or other guidelines for HCV., Conclusion: Physicians treating HCV infection among PWID attending OAT clinics recognized the importance of HCV testing and treatment. However, self-perceived competency related to HCV management and treatment was low, highlighting the importance of improved HCV education and training among physicians practicing in clinics offering OAT., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: People who inject drugs (PWID) are at high risk of hepatitis C virus (HCV) infection. Trends in HCV incidence and associated risk factors among PWID recruited between 1996 and 2012 in Vancouver, Canada were evaluated., Methods: Data were derived from a long-term cohort of PWID in Vancouver. Trends in HCV incidence were evaluated. Factors associated with time to HCV infection were assessed using Cox proportional hazards regression., Results: Among 2,589, 82% (n = 2,121) were HCV antibody-positive at enrollment. Among 364 HCV antibody-negative participants with recent (last 30 days) injecting at enrollment, 126 HCV seroconversions were observed [Overall HCV incidence density: 8.6 cases/100 person-years (py); 95% confidence interval (95% CI): 7.2, 10.1; HCV incidence density among those with injecting during follow-up: 11.5 cases/100 py; 95% CI 9.7, 13.6]. The overall HCV incidence density declined significantly from 25.0/100 py (95% CI: 20.2, 30.3) in 1996-99, as compared to 6.0/100 py (95% CI: 4.1, 8.5) in 2000-2005, and 3.1/100 py (95% CI: 2.0, 4.8) in 2006-2012. Among those with injecting during follow-up, the overall HCV incidence density declined significantly from 27.9/100 py (95% CI: 22.6, 33.6) in 1996-99, as compared to 7.5/100 py (95% CI: 5.1, 10.6) in 2000-2005, and 4.9/100 py (95% CI: 3.1, 7.4) in 2006-2012. Unstable housing, HIV infection, and injecting of cocaine, heroin and methamphetamine were independently associated with HCV seroconversion., Conclusions: HCV incidence has dramatically declined among PWID in this setting. However, improved public health strategies to prevent and treat HCV are urgently required to reduce HCV-associated morbidity and mortality.

The International Collaboration of Incident HIV and Hepatitis C in Injecting Cohorts (InC(3)) Study is an international multi-cohort project of pooled biological and behavioural data from nine prospective cohorts of people who inject drugs (PWID). InC(3) brings together researchers from Australia, Canada, USA and the Netherlands with expertise in epidemiology, biostatistics, clinical and behavioural sciences, virology and immunology to investigate research questions relevant to hepatitis C virus (HCV) and HIV outcomes. InC(3) was established to: (i) create a merged multi-cohort study of pooled data from well-characterized cohorts of PWID with prospective data on HIV and HCV infections, with a particular focus on HCV; (ii) facilitate new studies not possible within individual cohorts; and (iii) bring together researchers across disciplines to answer a broad range of research questions. Study cohorts identify acute HCV cases through follow-up of high-risk HCV antibody-negative PWID or through clinical referral networks. To date, data from 1986 to 2010 have been received from all contributing cohorts, with 821 HCV-infected and 1216 HCV-uninfected participants (overall, n = 2037). Data collected include demographics, host genetics, HCV ribonucleic acid testing, alanine aminotransferase testing, HIV/hepatitis B virus testing, HCV therapy, loss to follow-up and mortality. Potential collaborators should contact the InC(3) PI Dr Kimberley Page (kPage@psg.ucsf.edu) for further information.

Objectives: We evaluated the prevalence of primary HIV drug resistance in a population of 128 injection drug users (48 female) prior to initiating antiretroviral therapy., Methods: Genotypic and phenotypic profiles were obtained retrospectively for the period June 1996 to February 2007. Genotypic drug resistance was defined as the presence of a major mutation (IAS-USA table, 2007 revision), adding revertants at reverse transcriptase (RT) codon 215. Phenotypic drug resistance was defined as the fold change associated with >or=80% loss of the wild type virologic response due to viral resistance based on virtual phenotype analysis., Results: Genotypic drug resistance was uncommon, and was only identified in six (4.7%) cases, all in the RT gene (L100I, K103N, Y181C, M184V, Y188L, and T215D). There were no cases of multi-class or protease inhibitor (PI) resistance. However, polymorphisms in the protease and RT genes were extremely common. Phenotypic drug resistance was also identified in six (4.7%) patients, four in the RT gene (in patients with mutations K103N, Y181C, M184V and Y188L) and two the protease gene (in two patients with minor PI mutations). In addition, 25 (19.5%) of the patients had reduced susceptibility to PIs, defined as resistance>20% but <80% of the wild type virologic response, with no primary PI mutations detected in all these patients., Conclusion: The prevalence of primary HIV drug resistance was low in this population of injection drug users.

The treatment of injection drug users (IDUs) coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) presents multiple challenges, many of which could be addressed by the development of directly observed therapy programs. This is made all the more feasible by the validation of once-daily treatment regimens for HIV. We have demonstrated that virological suppression can be achieved and maintained in as many as 80% of active IDUs who have received highly active antiretroviral therapy for 48 months. This approach has now been validated in first- and second-line therapy, as well as for the treatment of bacterial infections in this population, achieving therapeutic results similar to those reported in the general population. The model is now being applied to the treatment of HCV infection, focusing on patients with infection due to HCV genotype 2 or 3, in whom the likelihood of response may exceed 80%. Our ultimate goal is to ensure that, even in treating IDUs in the inner city, no patient is left behind.