Hepatitis: Montaner JS

Hammer SM, Eron JJ, Reiss P, Schooley RT, Thompson MA, Walmsley S, Cahn P, Fischl MA, Gatell JM, Hirsch MS, Jacobsen DM, Montaner JS, Richman DD, Yeni PG, Volberding PA, Anonymous00064. · Division of Infectious Diseases, Columbia University College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA. · JAMA. · Pubmed #18677028 links to  free full text

Abstract: CONTEXT: The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection. OBJECTIVES: To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients. DATA SOURCES AND STUDY SELECTION: A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified. DATA EXTRACTION AND SYNTHESIS: Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus. CONCLUSIONS: New data and considerations support initiating therapy before CD4 cell count declines to less than 350/microL. In patients with 350 CD4 cells/microL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, >100,000 copies/mL) and rapidly declining CD4 cell count (>100/microL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial regimen must be individualized, particularly in the presence of comorbid conditions, but usually will include efavirenz or a ritonavir-boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine). Treatment failure should be identified and managed promptly, with the goal of therapy, even in heavily pretreated patients, being an HIV-1 RNA level below assay detection limits.

Hammer SM, Saag MS, Schechter M, Montaner JS, Schooley RT, Jacobsen DM, Thompson MA, Carpenter CC, Fischl MA, Gazzard BG, Gatell JM, Hirsch MS, Katzenstein DA, Richman DD, Vella S, Yeni PG, Volberding PA, Anonymous00173. · Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. · JAMA. · Pubmed #16905788 links to  free full text

Abstract: CONTEXT: Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field. OBJECTIVE: To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. DATA SOURCES AND STUDY SELECTION: A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. DATA EXTRACTION AND SYNTHESIS: Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. CONCLUSIONS: Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.

Braitstein P, Palepu A, Dieterich D, Benhamou Y, Montaner JS. · British Columbia Center for Excellence in HIV/AIDS, University of British Columbia, Vancouver, Canada. · AIDS. · Pubmed #15577534 No free full text.

Abstract: BACKGROUND: Although hepatitis C (HCV) treatment efficacy has improved in recent years, the majority of HIV/HCV-coinfected individuals may not enjoy the full benefits of these treatments and appropriate HIV management is crucial. Evidence is accumulating regarding the impact of HIV/HCV coinfection on the response to, and safety and tolerability of, antiretroviral therapy (ART) in this population. METHODS: Computerized, English-language literature searches of MEDLINE and PubMed databases (January 1985 to May 2004) for studies of HIV and HCV infection in humans to examine critically (a) the impact of HCV on the HIV virologic and immunologic response to ART; (b) the safety and tolerability of ART in coinfected individuals; and (c) the relationship between immune suppression and immune restoration on hepatic injury. RESULTS: Three key messages emerged regarding the use of ART in HIV/HCV-coinfected individuals: (a) although HCV appeared to have no impact on HIV virologic response, the data are equivocal regarding immunologic response; (b) morbidities associated with HCV infection, such as insulin resistance, diabetes, mitochondrial dysfunction, and liver inflammation, are also associated toxicities of ART, and (c) both immune suppression and restoration can contribute to the onset and acceleration of HCV-related liver disease. CONCLUSIONS: The CD4 cell count threshold for initiating ART in HIV/HCV-coinfected patients may be higher because of the impact of immune suppression and restoration on the onset of HCV-associated liver disease and the possibility of a blunted immune response to ART at lower CD4 cell counts. Further, overlapping morbidity between HCV-related mitochondrial and metabolic disease manifestations and ART toxicities warrant careful attention by clinicians.

Kerr T, Marshall BD, Miller C, Shannon K, Zhang R, Montaner JS, Wood E. · British Columbia Centre for Excellence in HIV/AIDS, St, Paul's Hospital, British Columbia, Canada. · BMC Public Health. · Pubmed #19493353 links to  free full text

Abstract: BACKGROUND: Street-involved youth contend with an array of health and social challenges, including elevated rates of blood-borne infections and mortality. In addition, there has been growing concern regarding high-risk drug use among street-involved youth, in particular injection drug use. We undertook this study to examine the prevalence of injection drug use and associated risks among street-involved youth in Vancouver, Canada. METHODS: From September 2005 to November 2007, baseline data were collected for the At-Risk Youth Study (ARYS), a prospective cohort of street-recruited youth aged 14 to 26 in Vancouver, Canada. Using multiple logistic regression, we compared youth with and without a history of injection. RESULTS: The sample included 560 youth among whom the median age was 21.9 years, 179 (32%) were female, and 230 (41.1%) reported prior injection drug use. Factors associated with injection drug use in multivariate analyses included age >or= 22 years (adjusted odds ratio [AOR] = 1.18, 95% CI: 1.10-1.28); sex work involvement (AOR = 2.17, 95% CI: 1.35-3.50); non-fatal overdose (AOR = 2.10, 95% CI: 1.38-3.20); and hepatitis C (HCV) infection (AOR = 22.61, 95% CI: 7.78-65.70). CONCLUSION: These findings highlight an alarmingly high prevalence of injection drug use among street-involved youth and demonstrate its association with an array of risks and harms, including sex work involvement, overdose, and HCV infection. These findings point to the need for a broad set of policies and interventions to prevent the initiation of injection drug use and address the risks faced by street-involved youth who are actively injecting.

Marshall BD, Kerr T, Livingstone C, Li K, Montaner JS, Wood E. · British Columbia Centre for Excellence in HIV/AIDS, St, Paul's Hospital, 608-1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada . · Harm Reduct J. · Pubmed #19019253 links to  free full text

Abstract: ABSTRACT: Aboriginal people experience a disproportionate burden of HIV infection among the adult population in Canada; however, less is known regarding the prevalence and characteristics of HIV positivity among drug-using and street-involved Aboriginal youth. We examined HIV seroprevalence and risk factors among a cohort of 529 street-involved youth in Vancouver, Canada. At baseline, 15 (2.8%) were HIV positive, of whom 7 (46.7%) were Aboriginal. Aboriginal ethnicity was a significant correlate of HIV infection (odds ratio = 2.87, 95%CI: 1.02 - 8.09). Of the HIV positive participants, 2 (28.6%) Aboriginals and 6 (75.0%) non-Aboriginals reported injection drug use; furthermore, hepatitis C co-infection was significantly less common among Aboriginal participants (p = 0.041). These findings suggest that factors other than injection drug use may promote HIV transmission among street-involved Aboriginal youth, and provide further evidence that culturally appropriate and evidence-based interventions for HIV prevention among Aboriginal young people are urgently required.

Matsukura M, Chu FF, Au M, Lu H, Chen J, Rietkerk S, Barrios R, Farley JD, Montaner JS, Montessori VC, Walker DC, Côté HC. · Department of Pathology and Laboratory Medicine, University of British Columbia, Canada. · AIDS. · Pubmed #18525271 No free full text.

Abstract: Liver mitochondrial toxicity is a concern, particularly in HIV/hepatitis C virus (HCV) coinfection. Liver biopsies from HIV/HCV co-infected patients, 14 ON-highly active antiretroviral therapy (HAART) and nine OFF-HAART, were assessed by electron microscopy quantitative morphometric analyses. Hepatocytes tended to be larger ON-HAART than OFF-HAART (P = 0.05), but mitochondrial volume, cristae density, lipid volume, mitochondrial DNA and RNA levels were similar. We found no evidence of increased mitochondrial toxicity in individuals currently on HAART, suggesting that concomitant HAART should not delay HCV therapy.

Blondin D, Crawford RI, Kerr T, Zhang R, Tyndall MW, Montaner JS, Wood E. · University of Calgary, AB. · J Cutan Med Surg. · Pubmed #18346403 No free full text.

Abstract: BACKGROUND: Drug use patterns and serious bloodborne infections commonly have dermatologic manifestations among illicit injection-drug users (IDUs). OBJECTIVE: To assess how self-reported skin conditions of IDUs may correlate with underlying infectious diseases after adjustment for drug use patterns. METHODS: Prospective analysis of factors associated with self-reports of skin rashes, cellulitis, oral lesions, and lymphadenopathy obtained from 1,065 IDUs enrolled in a large cohort study. Variables potentially associated with each outcome were evaluated using multivariate generalized estimating equations. RESULTS: In multivariate analyses, drug use patterns were associated with cellulitis, whereas human immunodeficiency virus (HIV) infection and hepatitis C (HCV) were not. HCV infection was independently associated with skin rashes (odds ratio [OR] 1.85; 95% CI 1.17-2.94). HIV infection was independently associated with lymphadenopathy (OR 2.00; 95% CI 1.52-2.63), skin rash (OR 2.12; 95% CI 1.57-2.86), and oral lesions (OR 14.95; 95% CI 9.41-23.76). CONCLUSIONS: Self-reports of IDUs, which could easily be obtained as part of a functional inquiry in a clinical setting, correlate with specific drug use patterns and underlying bloodborne infections.

Gutiérrez S, Guillemi S, Jahnke N, Montessori V, Harrigan PR, Montaner JS. · BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, University of British Columbia, Vancouver, Canada. · Clin Infect Dis. · Pubmed #18181733 No free full text.

Abstract: We summarize the clinical history and laboratory results following the introduction of tenofovir among 6 patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) who presented with severe liver disease while receiving lamivudine-based highly active antiretroviral therapy. In all cases, the introduction of tenofovir led to a sustained undetectable HBV and HIV loads, with marked clinical and laboratory improvement in liver function. We provide supporting evidence for the role of tenofovir in the management of advanced HBV infection in HIV-positive patients after the development of lamivudine resistance.

Phillips E, Gutiérrez S, Jahnke N, Yip B, Lima VD, Hogg RS, Harrigan PR, Montaner JS. · British Columbia Centre for Excellence in HIV/AIDS, Providence Healthcare, St Paul's Hospital, 667-1081 Burrard Street, Vancouver, BC, Canada. · AIDS. · Pubmed #17630551 No free full text.

Abstract: OBJECTIVE: To assess risks factors and outcomes associated with nevirapine hypersensitivity reactions, and to determine the effect of hypersensitivity as a modifier of the association between hepatitis C virus (HCV) infection and mortality among antiretroviral drug-naive patients. METHODS: The primary endpoint was hypersensitivity reactions in a population-based cohort of antiretroviral therapy-naive HIV-individuals, 18 years or older in British Columbia, Canada, who started triple antiretroviral therapy with nevirapine between May 1997 and June 2003. Univariate and multivariate analyses were performed to identify predictors of nonaccidental mortality in the subgroup of patients with known HCV serostatus. RESULTS: A total of 66 (9.6%) of 685 patients met the definition for hypersensitivity reactions. In the univariate logistic regression analysis, no variables were identified as risk factors. In multivariate survival analyses conducted to identify characteristics associated with nonaccidental mortality, patients with both HCV coinfection and hypersensitivity reactions had a higher risk of death (hazard ratio, 7.12; 95% confidence interval, 2.73-18.53; P < 0.001) compared with those who did not have HCV coinfection or hypersensitivity reaction. CONCLUSION: Results of this study suggest that the hypersensitivity reaction behaves as an effect modifier of the association between HCV infection and mortality in this cohort of antiretroviral drug-naive HIV-positive patients. These results support the current recommendation against the use of nevirapine in HIV/HCV-coinfected patients.

Tyndall MW, Wood E, Zhang R, Lai C, Montaner JS, Kerr T. · Department of Medicine, University of British Columbia, Vancouver Hospital, 2775 Laurel Street, Vancouver, V5Z 1M9, Canada. · Harm Reduct J. · Pubmed #17176481 links to  free full text

Abstract: North America's first government sanctioned medically supervised injection facility (SIF) was opened during September 2003 in Vancouver, Canada. This was in response to a large open public drug scene, high rates of HIV and hepatitis C transmission, fatal drug overdoses, and poor health outcomes among the city's injection drug users. Between December 2003 and April 2005, a representative sample of 1,035 SIF participants were enrolled in a prospective cohort that required completing an interviewer-administered questionnaire and providing a blood sample for HIV testing. HIV infection was detected in 170/1007 (17%) participants and was associated with Aboriginal ethnicity (adjusted Odds Ratio [aOR], 2.70, 95% Confidence Interval [95% CI], 1.84-3.97), a history of borrowing used needles/syringes (aOR, 2.0, 95% CI, 1.37-2.93), previous incarceration (aOR, 1.87, 95% CI, 1.11-3.14), and daily injection cocaine use (aOR, 1.42, 95% CI, 1.00-2.03). The SIF has attracted a large number of marginalized injection drug users and presents an excellent opportunity to enhance HIV prevention through education, the provision of sterile injecting equipment, and a supervised environment to self-inject. In addition, the SIF is an important point of contact for HIV positive individuals who may not be participating in HIV care and treatment.

Braitstein P, Li K, Kerr T, Montaner JS, Hogg RS, Wood E. · British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, Canada. · AIDS Care. · Pubmed #16971276 No free full text.

Abstract: Access to HCV (Hepatitis C virus) care for HIV/HCV-co-infected patients is an urgent public health concern. The objective of the present study was to describe the self-reported health status of HIV/HCV-co-infected and HCV-mono-infected injection drug users and to describe their access to HCV-related care. Beginning in May 1996, persons who had injected illicit drugs in the previous month were recruited into the Vancouver Injection Drug User Study (VIDUS). At baseline and then semi-annually, participants complete an interviewer-administered questionnaire. Blood is drawn at each semi-annual interview and tested for HIV and Hepatitis C infection. Data for this descriptive, cross-sectional study were drawn from the most recent of either the July 2003 or December 2003 nurse-administered questionnaire. Statistics used were the chi-square, Wilcoxon Rank Sum and Student's t-test. Logistic regression was used to examine factors independently associated with accessing HCV care. There were 707 individuals eligible for this analysis, including 240 HIV/HCV-co-infected and 467 HCV-mono-infected persons. Co-infected individuals were more likely to be female, younger, of Aboriginal ethnicity and less likely to use heroin daily. The HCV-mono-infected group tended to report higher rates of HCV-related symptoms, including fatigue, liver pain, nausea, night-sweats and stomach pain. However, it was the HIV/HCV-co-infected group who were more likely to report that they believed their hepatitis C was affecting them. The HIV/HCV-co-infected group were also more likely to report having received any hepatitis-related follow-up care, including blood work, liver biopsies and referrals to specialists. In logistic regression analysis, factors independently associated with ever receiving any hepatitis C related follow-up were HIV/HCV-co-infection (AOR 3.1; 95% CI: 2-4.7), being older (AOR 1.04; 95% CI: 1.02-1.06 per year older), using heroin daily (AOR 0.54; 95% CI: 0.36-0.82) and believing that hepatitis C was affecting one's health (AOR 1.4; 95% CI: 1.0-2.1). In conclusion, our data indicate more HCV healthcare utilization among those HIV/HCV-co-infected.

Palepu A, Tyndall MW, Joy R, Kerr T, Wood E, Press N, Hogg RS, Montaner JS. · Centre for Health Evaluation and Outcome Sciences, St. Paul's Hospital, University of British Columbia, BC, Canada. · Drug Alcohol Depend. · Pubmed #16542797 No free full text.

Abstract: OBJECTIVE: We examined the association of methadone maintenance therapy (MMT) with highly active antiretroviral therapy (HAART) adherence and HIV treatment outcomes among a cohort of HIV/HCV co-infected injection drug users (IDUs). METHODS: We obtained demographic, drug use, and addiction care history from the Vancouver Injection Drug User Study (VIDUS), which is an open cohort study of IDUs. The questionnaires were longitudinally linked to the British Columbia HIV/AIDS Drug Treatment Program to obtain HAART adherence and HIV treatment outcome data. There were 278 VIDUS participants who accessed HAART from August 1, 1996 to November 24, 2003. We constructed longitudinal logistic models using generalized estimating equations to examine the independent associations between methadone maintenance therapy and the following outcomes: HAART adherence; plasma HIV-1 RNA suppression; and CD4 cell rise of 100cells/mm(3). RESULTS: Among participants who reported at least weekly heroin use, MMT was independently associated with lower odds of subsequent weekly heroin use during the follow-up period (adjusted odds ratio; 95% confidence interval [AOR; 95% CI]: 0.24; 0.14-0.40). We also found that MMT was positively associated with adherence (AOR 1.52; 95% CI 1.16-2.00), HIV-1 RNA suppression (AOR 1.34; 95% CI 1.00-1.79), and CD4 cell count rise (AOR 1.58; 95% CI 1.26-1.99). CONCLUSIONS: Among HIV/HCV co-infected IDUs on HAART, enrollment in MMT was associated with reduced heroin use, and improved adherence, HIV-1 RNA suppression and CD4 cell count response. Integrating opiate addiction care and HIV care may provide improved health outcomes for this vulnerable population and should be further explored.

Moore DM, Hogg RS, Braitstein P, Wood E, Yip B, Montaner JS. · BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada. · Antivir Ther. · Pubmed #16518968 No free full text.

Abstract: BACKGROUND: Patients coinfected with hepatitis C virus (HCV) and HIV experience higher mortality rates than patients infected with HIV alone. We designed a study to determine whether risks for later mortality are similar for HCV-positive and HCV-negative individuals when subjects are stratified on the basis of baseline CD4+ T-cell counts. METHODS: Antiretroviral-naive individuals, who initiated highly active antiretroviral therapy (HAART) between 1996 and 2002 were included in the study. HCV-positive and HCV-negative individuals were stratified separately by baseline CD4+ T-cell counts of 50 cell/microl increments. Cox-proportional hazards regression was used to model the effect of these strata with other variables on survival. RESULTS: CD4+ T-cell strata below 200 cells/microl, but not above, imparted an increased relative hazard (RH) of mortality for both HCV-positive and HCV-negative individuals. Among HCV-positive individuals, after adjustment for baseline age, HIV RNA levels, history of injection drug use and adherence to therapy, only CD4+ T-cell strata of <50 cells/microl (RH=4.60; 95% confidence interval [CI] 2.72-7.76) and 50-199 cells/microl (RH=2.49; 95% CI 1.63-3.81) were significantly associated with increased mortality when compared with those initiating therapy at cell counts >500 cells/microl. The same baseline CD4+ T-cell strata were found for HCV-negative individuals. CONCLUSION: In a within-groups analysis, the baseline CD4+ T-cell strata that are associated with increased RHs for mortality are the same for HCV-positive and HCV-negative individuals initiating HAART. However, a between-groups analysis reveals a higher absolute mortality risk for HCV-positive individuals.

Braitstein P, Justice A, Bangsberg DR, Yip B, Alfonso V, Schechter MT, Hogg RS, Montaner JS. · British Columbia Center for Excellence in HIV/AIDS, University of British Columbia, Vancouver, Canada. · AIDS. · Pubmed #16439865 No free full text.

Abstract: OBJECTIVE: To characterize the impact of hepatitis C (HCV) serostatus on adherence to antiretroviral treatment (ART) among HIV-infected adults initiating ART. METHODS: The British Columbia HIV/AIDS Drug Treatment Program distributes, at no cost, all ART in this Canadian province. Eligible individuals used triple combination ART as their first HIV therapy and had documented HCV serology. Statistical analyses used parametric and non-parametric methods, including multivariate logistic regression. The primary outcome was > or = 95% adherence, defined as receiving > or = 95% of prescription refills during the first year of antiretroviral therapy. RESULTS: There were 1186 patients eligible for analysis, including 606 (51%) positive for HCV antibody and 580 (49%) who were negative. In adjusted analyses, adherence was independently associated with HCV seropositivity [adjusted odds ratio (AOR), 0.48; 95% confidence interval (CI), 0.23-0.97; P = 0.003], higher plasma albumin levels (AOR, 1.07; 95% CI, 1.01-1.12; P = 0.002) and male gender (AOR, 2.53; 95% CI, 1.04-6.15; P = 0.017), but not with injection drug use (IDU), age or other markers of liver injury. There was no evidence of an interaction between HCV and liver injury in adjusted analyses; comparing different strata of HCV and IDU confirmed that HCV was associated with poor adherence independent of IDU. CONCLUSIONS: HCV-coinfected individuals and those with lower albumin are less likely to be adherent to their ART.

Braitstein P, Zala C, Yip B, Brinkhof MW, Moore D, Hogg RS, Montaner JS. · British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver, Canada. · J Infect Dis. · Pubmed #16362890 No free full text.

Abstract: BACKGROUND: We sought to characterize the impact that hepatitis C virus (HCV) infection has on CD4 cells during the first 48 weeks of antiretroviral therapy (ART) in previously ART-naive human immunodeficiency virus (HIV)-infected patients. METHODS: The HIV/AIDS Drug Treatment Programme at the British Columbia Centre for Excellence in HIV/AIDS distributes all ART in this Canadian province. Eligible individuals were those whose first-ever ART included 2 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor and who had a documented positive result for HCV antibody testing. Outcomes were binary events (time to an increase of > or = 75 CD4 cells/mm3 or an increase of > or = 10% in the percentage of CD4 cells in the total T cell population [CD4 cell fraction]) and continuous repeated measures. Statistical analyses used parametric and nonparametric methods, including multivariate mixed-effects linear regression analysis and Cox proportional hazards analysis. RESULTS: Of 1186 eligible patients, 606 (51%) were positive and 580 (49%) were negative for HCV antibodies. HCV antibody-positive patients were slower to have an absolute (P<.001) and a fraction (P = .02) CD4 cell event. In adjusted Cox proportional hazards analysis (controlling for age, sex, baseline absolute CD4 cell count, baseline pVL, type of ART initiated, AIDS diagnosis at baseline, adherence to ART regimen, and number of CD4 cell measurements), HCV antibody-positive patients were less likely to have an absolute CD4 cell event (adjusted hazard ratio [AHR], 0.84 [95% confidence interval [CI], 0.72-0.98]) and somewhat less likely to have a CD4 cell fraction event (AHR, 0.89 [95% CI, 0.70-1.14]) than HCV antibody-negative patients. In multivariate mixed-effects linear regression analysis, HCV antibody-negative patients had increases of an average of 75 cells in the absolute CD4 cell count and 4.4% in the CD4 cell fraction, compared with 20 cells and 1.1% in HCV antibody-positive patients, during the first 48 weeks of ART, after adjustment for time-updated pVL, number of CD4 cell measurements, and other factors. CONCLUSION: HCV antibody-positive HIV-infected patients may have an altered immunologic response to ART.

Collins CL, Kerr T, Tyndall MW, Marsh DC, Kretz PS, Montaner JS, Wood E. · British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, BC. · Can J Public Health. · Pubmed #16238151 No free full text.

Abstract: Many cities are experiencing ongoing infectious disease epidemics and substantial community harm as a result of illicit drug use. In an effort to reduce these public order and public health concerns, consideration has been given to the opening in Vancouver of a safer smoking facility (SSF). The present review was conducted to examine if there is a rationale to support the evaluation of a SSF in the Canadian context. Available evidence suggests that conventional drug control strategies are insufficient to address the health and community harms of non-injection drug use, and that the public order benefits of supervised injection facilities may be relevant to SSFs. In addition, there is persuasive evidence to suggest there is potential for blood-borne disease transmission through the sharing of smoking paraphernalia, and the potential for SSFs to address this concern is a pressing public health question. Also relevant to this topic are interventions to prevent transition into injection drug use, and SSFs may also be evaluated as a potential strategy to address this concern.

Wood E, Kerr T, Stoltz J, Qui Z, Zhang R, Montaner JS, Tyndall MW. · Division of Epidemiology and Population Health, British Columbia Center for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, Canada. · Public Health. · Pubmed #16214189 No free full text.

Abstract: BACKGROUND: North America's first medically supervised safer injection facility (SIF) for illicit drug users was opened in Vancouver, Canada on 22 September 2003. We examined the prevalence and correlates of hepatitis C (HCV) infection among a representative cohort of SIF users. METHODS: Users of the Vancouver SIF were selected at random and asked to enrol in the Scientific Evaluation of Supervised Injecting (SEOSI) cohort. At baseline, venous blood samples were collected and an interviewer-administered questionnaire was performed. Participants who were HCV-positive were compared with HCV-negative subjects using bivariate and logistic regression analyses. RESULTS: Between 1 December 2003 and 30 July 2004, 691 participants were enrolled into the SEOSI cohort, among whom 605 (87.6%) were HCV-positive at baseline. Factors independently associated with HCV infection in logistic regression analyses included: involvement with the sex trade [adjusted odds ratio (AOR) 3.7, 95% confidence interval (CI) 2.1-6.1], history of borrowing syringes (AOR 1.8, 95%CI 1.1-2.9), and history of incarceration (AOR 2.6, 95%CI 1.5-4.4). Daily heroin use was protective against HCV infection (AOR 0.6, 95%CI 0.3-0.9). CONCLUSION: The SIF has attracted injection drug users with a high burden of HCV infection and a substantial proportion of uninfected individuals. Although cross-sectional, this study provides some insight into historical risks for HCV infection among this population, and prospective follow-up of this cohort will be useful to determine if use of the SIF is associated with reduced risk behaviour and HCV incidence.

Braitstein P, Montessori V, Chan K, Montaner JS, Schechter MT, O'Shaughnessy MV, Hogg RS. · Division of Epidemiology and Population Health, British Columbia Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, Canada. · AIDS Care. · Pubmed #16036236 No free full text.

Abstract: The objective of the study was to describe the additional burden generated by hepatitis C (HCV) infection among HIV-infected individuals as measured by self-reported quality of life, depression and fatigue. The provincial HIV/AIDS Drug Treatment Program (DTP) distributes all antiretroviral medication in the province of British Columbia. Eligibility for accessing antiretrovirals is based on published guidelines commensurate with the International AIDS Society. Each participant is asked to complete a self-administered mailed questionnaire that includes patient sociodemographic information, quality of life measures (Medical Outcomes Study-Short Form (MOS-SF), mental health issues (Centre for Epidemiological Studies Depression scale (CESD) and fatigue information. HIV-HCV co-infected individuals were compared to HIV mono-infected individuals using parametric and nonparametric methods. Multivariate logistic regression was used to examine the impact of hepatitis C on quality of life, depression and fatigue, after controlling for sociodemographics and HIV-specific clinical characteristics. Of the 4,134 individuals who were sent a HIV/AIDS DTP survey in 1999, 2000 or 2001, 484 participants both returned one and had an HCV-antibody test result on file. Of the 484 participants eligible for this analysis, 105 (22%) were HCV-positive. In comparison to the 379 (78%) patients testing negative for HCV, a larger proportion of co-infected patients were female (18% versus 3%, p<0.001), aboriginal (20% versus 3%, p<0.001), had ever injected drugs (79% versus 5%, p<0.001), were unemployed (91% versus 49%, p<0.001) and lived in unstable housing (19% versus 1%, p<0.001) at the time they completed the survey. Co-infected patients reported more symptoms consistent with depression, increased fatigue and poorer quality of life. However, using multivariate modeling, it was determined that the impact of HCV on quality of life, depression and fatigue was better explained by the sociodemographic factors related to poverty and injection drug use, than by HCV itself. In conclusion, individuals co-infected with HIV and HCV represent a patient population with significant physical and mental health challenges. Although these patients experience poorer quality of life, increased depression and fatigue, this experience appears to be primarily related to socio-economic issues rather than HCV infection.

Braitstein P, Yip B, Montessori V, Moore D, Montaner JS, Hogg RS. · Institute for Social and Preventive Medicine, University of Berne, Berne, Switzerland. · CMAJ. · Pubmed #16027432 links to  free full text

Abstract: BACKGROUND: We examined the effect of hepatitis C virus (HCV) seropositivity on risk of death among people receiving their first antiretroviral treatment (ART) for HIV infection. METHODS: In British Columbia, the HIV/ AIDS Drug Treatment Program is the only source of free ART. Patients who initiated a triple-drug ART regimen between July 31, 1996, and July 31, 2000, were included if they were ART-naive and had baseline HCV serological data. Outcomes of interest for survival analysis were deaths from natural and HIV-related causes, with a data cutoff of June 30, 2003. RESULTS: Of 1186 eligible subjects, 606 (51%) were HCV positive and 580, negative. Fewer HCV-positive people were male (78% v. 93%, p < 0.001) and had an AIDS diagnosis at baseline (11% v. 15%, p = 0.028). Their CD4 fraction was significantly higher at baseline (19% v. 16% of T lymphocytes, p < 0.001) but their absolute CD4 counts, log HIV viral load and the type of ART initiated were similar to those of HCV negative people. Of 163 deaths (from natural causes only) during the study period, 118 (19%) were in HCV positive and 45 (8%) in HCV negative patients (p < 0.001); of the 114 deaths attributed to HIV infection, these proportions were 79 (13%) versus 35 (6%; p < 0.001). After adjustment for potential confounders, HCV seropositivity remained predictive of death (adjusted hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.50- 3.21, p < 0.001), especially HIV-related death (adjusted HR 1.75, 95% CI 1.13- 2.72, p = 0.012). INTERPRETATION: In this population-based HIV treatment program, we found HCV seropositivity to be an independent predictor of mortality, especially death related to HIV infection.

Collins CL, Kerr T, Kuyper LM, Li K, Tyndall MW, Marsh DC, Montaner JS, Wood E. · British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6. · J Urban Health. · Pubmed #15872188 No free full text.

Abstract: Many cities are experiencing infectious disease epidemics and substantial community harms as a result of illicit drug use. Although medically supervised smoking facilities (SSFs) remain untested in North America, local health officials in Vancouver are considering to prepare a submission to Health Canada for an exemption to open Canada's first SSF for evaluation. Reluctance of health policymakers to initiate a pilot study of SSFs may be due in part to outstanding questions regarding the potential uptake and community impacts of the intervention. This study was conducted to evaluate the prevalence and correlates of willingness to use an SSF among illicit drug smokers who are enrolled in the Vancouver Injection Drug Users Study. Participants who reported actively smoking cocaine, heroin, or methamphetamine who returned for follow-up between June 2002 and December 2002 were eligible for these analyses. Those who reported willingness to use an SSF were compared with those who were unwilling to use an SSF by using logistic regression analyses. Four hundred and forty-three participants were eligible for this study. Among respondents, 124 (27.99%) expressed willingness to attend an SSF. Variables that were independently associated with willingness to attend an SSF in multivariate analyses included sex-trade work (adjusted odds ratio [AOR]=1.85), crack pipe sharing (AOR=2.24), and residing in the city's HIV epicentre (AOR =1.64). We found that participants who demonstrated a willingness to attend an SSF were more likely to be involved in the sex trade and share crack pipes. Although the impact of SSFs in North America can only be quantified by scientific evaluation, these data indicate a potential for public health and community benefits if SSFs were to become available.

Miller CL, Wood E, Spittal PM, Li K, Frankish JC, Braitstein P, Montaner JS, Schechter MT. · British Columbia Centre for Excellence in HIV/AIDS, Vancouver, and Department of Health Care and Epidemiology, University of British Columbia, Vancouver, Canada. · J Acquir Immune Defic Syndr. · Pubmed #15167294 No free full text.

Abstract: The purpose of this study was to determine the prevalence and incidence of HIV and hepatitis C virus (HCV) coinfection among young (aged 29 years or younger) injection drug users (IDUs) and to compare sociodemographic and risk characteristics between (HIV/HCV) coinfected, monoinfected, or HIV- and HCV-negative youth. Data were collected through the Vancouver Injection Drug Users Study (VIDUS). To date, more than 1400 IDUs have been enrolled and followed, of whom 479 were aged 29 years or younger. Semiannually, participants have completed an interviewer-administered questionnaire and have undergone serologic testing for HIV and HCV. Univariate and multivariate logistic regression analyses were undertaken to investigate predictors of baseline coinfection. Cox regression models with time-dependent covariates were used to identify predictors of time to secondary infection seroconversion. A Cochran-Armitage trend test was used to determine risk associations across 3 categories: no infection, monoinfection, and coinfection. Of the 479 young injectors, 78 (16%) were coinfected with HIV and HCV at baseline and a further 45 (15%) with follow-up data became coinfected during the study period. Baseline coinfection was independently associated with being female, being aboriginal, older age, greater number of years injecting, and living in the IDU epicenter. Factors independently associated with time to secondary infection seroconversion were borrowing needles and greater than once-daily cocaine injection, and accessing methadone maintenance therapy in the previous 6 months was protective. There were clear trends across the 3 categories for increasing proportions of female subjects, aboriginal subjects, older age, greater number of years injecting, living in the IDU epicenter, and daily cocaine use. There were a shocking number of youth living with coinfection, particularly female and aboriginal youth. The median number of years injecting for youth seroconverting to a secondary infection was 3 years, suggesting that appropriate public health interventions should be implemented immediately.

Wood E, Kerr T, Montaner JS, Strathdee SA, Wodak A, Hankins CA, Schechter MT, Tyndall MW. · British Columbia Centre for Exellence in HIV/AIDS, St Paul's Hospital, Vancouver, Canada. · Lancet Infect Dis. · Pubmed #15120347 No free full text.

Abstract: Many cities throughout the world are experiencing ongoing infectious disease and overdose epidemics among illicit injection drug users (IDUs). In particular, HIV and hepatitis C virus (HCV) have become endemic in many settings and bacterial infections, such as endocarditis, have become extremely common among this population. In an effort to reduce these public health concerns, in September 2003, Vancouver, Canada, opened a pilot medically supervised safer- injecting facility (SIF), where IDUs can inject pre-obtained illicit drugs under the supervision of medical staff. Before and since the facility's opening, there has been a substantial misunderstanding about the rationale for evaluating SIF as a public-health strategy. This article outlines the evidence and rationale in support of the Canadian initiative. This rationale involves limitations in conventionally applied drug-control efforts, and gaps in current public-health policies in controlling the spread of infectious diseases, and the incidence of overdose among IDUs.

Brumme ZL, Chan KJ, Dong WW, Mo T, Wynhoven B, Hogg RS, Montaner JS, O'Shaughnessy MV, Harrigan PR. · BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada. · AIDS. · Pubmed #12351953 No free full text.

Abstract: INTRODUCTION: Co-infection with GBV-C ('Hepatitis G' virus) appears to be associated with slower disease progression in HIV-infected, untreated individuals. We wished to determine whether detection of GBV-C RNA was associated with differential response to HIV therapy in a population-based cohort of 461 individuals initiating antiretroviral therapy between June 1996 and August 1998, in British Columbia, Canada. METHODS: The presence of GBV-C RNA in plasma was identified by nested RT-PCR, using detection of HIV RNA as a positive control. Time to virological success [achieving HIV plasma viral load (pVL) < or = 500 copies/ml], virological failure (subsequent confirmed pVL > 500 copies/ml) and immunological failure (confirmed CD4 cell count below baseline) were assessed by Kaplan-Meier methods and Cox proportional hazard regression. RESULTS: Of the 441 individuals for whom results were available, 90 (20.4%) had detectable plasma GBV-C RNA. GBV-C RNA was significantly associated with a lower HIV pVL at baseline (P = 0.004). In univariate and multivariate Cox models, GBV-C RNA positive and negative individuals did not differ with respect to time to virological success [risk ratio (RR), 0.98; 95% confidence interval (CI), 0.75-1.27], time to virological failure (RR, 1.10; 95% CI, 0.74-1.65), or time to immunological failure (RR, 1.09; 95% CI, 0.73-1.63). There was no correlation between detection of GBV-C RNA and mutations in the human chemokine receptors CCR5 and CX CR1, or HIV viral tropism as predicted by the HIV envelope sequence (P > 0.1). CONCLUSION: GBV-C viremia is relatively common in individuals seeking treatment for HIV infection; however, it does not appear to have any effect on initial antiretroviral therapy response.

Miller CL, Johnston C, Spittal PM, Li K, Laliberté N, Montaner JS, Schechter MT. · British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver, British Columbia, Canada. · Hepatology. · Pubmed #12198668 No free full text.

Abstract: The objective of this study was to compare sociodemographic, drug, and sexual risk characteristics between hepatitis C virus (HCV) baseline positive and negative young (13-24 years) injection drug users (IDUs) and to determine prospective risk factors for HCV seroconversion among the youth. Data were collected through the Vancouver Injection Drug Users Study (VIDUS). To date, more than 1,400 Vancouver-area IDUs have been enrolled and followed up; 234 were aged 24 years and younger. Semiannually, participants have completed an interviewer-administered questionnaire and have undergone serologic testing for human immunodeficiency virus (HIV) and HCV. Univariate and multivariate logistic regression analyses were undertaken to investigate predictors of baseline HCV positivity. In the multivariate analyses, Cox regression models with time-dependent covariates were used to identify predictors of HCV seroconversion. Of the 232 young injectors, 107 (46%) were HCV positive at baseline and a further 37 HCV seroconverted during the study period for an incidence rate of 37.3 per 100 person-years. Baseline positivity was associated with Aboriginal ancestry, older age, greater number of years injecting drugs, recent incarceration, sex trade work, more than 100 lifetime sexual partners, a previous sexually transmitted disease, living in the IDU epicenter, and injection more than once per day of heroin, cocaine, and speedball. Factors independently associated with HCV seroconversion were having a partner who uses injection drugs, requiring help to inject, and injection of cocaine more than once daily. In conclusion, unlike older IDUs, more than one half of young injectors were HCV negative at recruitment. Thus, there is a window of opportunity for prevention. However, the incidence rate of HCV among these young IDUs is alarming, suggesting that the opportunity to intervene is exceedingly small.

Delgado J, Harris M, Tesiorowski A, Montaner JS. · Grupo Estudio Hepatitis Virica y SIDA, Hospital Universitario Virgen del Rocio, Seville, Spain. · Clin Infect Dis. · Pubmed #11712096 No free full text.

Abstract: Symptomatic lactic acidemia was seen in 5 human immunodeficiency virus-positive patients receiving combination therapy that included stavudine and > or =1 other nucleoside. Peak venous lactic acid levels of 3.1-7.4 mmol/L (normal range, 0.5-2.1 mmol/L) were associated with fatigue and rapid weight loss, whereas withdrawal of antiretrovirals led to normalization of venous lactic acid levels, symptomatic improvement, and weight gain. Resumption of an altered therapeutic regimen, which did not include stavudine but did include other nucleosides in 4 of 5 cases, did not result in recurrence of the syndrome after up to 126 days.