Hepatitis: Cooper CL

Cooper CL. · No affiliation provided · J Infect Dis. · Pubmed #17674305 No free full text.

This publication has no abstract.

Cooper CL. · University of Ottawa Hospital, Division of Infectious Diseases, The Ottawa Hospital, Ottawa, Canada. · J Addict Dis. · Pubmed #18681192 No free full text.

Abstract: Hepatitis C (HCV) infection in substance addicted patients is common and represents a therapeutically challenging co-morbidity. Alcohol and perhaps other substances of abuse directly influence the natural progression of HCV disease. Concurrent mental health illness, poor socioeconomic status, and unstructured life styles are often incompatible with safe and successful delivery of HCV treatment. These issues and their effect on treatment suitability and outcome are considered in this review. Funding for HCV-addiction research and strong political backing for interventions proven to benefit those struggling with addiction are paramount to increasing access to and uptake of HCV treatment. These interventions include substance cessation programs, safe injection settings to reduce HCV incidence and multidisciplinary teams to facilitate HCV treatment provision.

Cooper CL. · University of Ottawa Hospital, Division of Infectious Diseases-The Ottawa Hospital, The Ottawa Hospital-General Campus, Room G12, 501 Smyth Road, Ottawa, ON, Canada, K1H 8L6. · Dig Dis Sci. · Pubmed #18041585 No free full text.

Abstract: Combination antiretroviral therapy often controls HIV disease, may indirectly slow HCV progression, and creates an immune environment which may optimize HCV drug therapy response. Monitoring for antiretroviral-related liver adverse events is vital. However, this complication infrequently causes clinically significant liver toxicity. HCV antiviral therapy should, in most cases, be reserved for those abstaining from alcohol and achieving HIV RNA suppression and immune restoration on combination antiretroviral therapy or for those with nadir CD4 counts above 350 cells/mul. Given the high prevalence of HBV and HCV co-infection, chronic viral hepatitis will influence the health and treatment of HIV-infected individuals for the foreseeable future.

Neuman MG, Sha K, Esguerra R, Zakhari S, Winkler RE, Hilzenrat N, Wyse J, Cooper CL, Seth D, Gorrell MD, Haber PS, McCaughan GW, Leo MA, Lieber CS, Voiculescu M, Buzatu E, Ionescu C, Dudas J, Saile B, Ramadori G. · In Vitro Drug Safety and Biotechnology, Department of Pharmacology, Biophysics and Global Health, Institute of Drug Research, University of Toronto, Toronto, ON, Canada. · Dig Dis Sci. · Pubmed #17994278 No free full text.

Abstract: Hepatitis C viral infection (HCV) results in liver damage leading to inflammation and fibrosis of the liver and increasing rates of hepatic decompensation and hepatocellular carcinoma (HCC). However, the host's immune response and viral determinants of liver disease progression are poorly understood. This review will address the determinants of liver injury in chronic HCV infection and the risk factors leading to rapid disease progression. We aim to better understand the factors that distinguish a relatively benign course of HCV from one with progression to cirrhosis. We will accomplish this task by discussion of three topics: (1) the role of cytokines in the adaptive immune response against the HCV infection; (2) the progression of fibrosis; and (3) the risk factors of co-morbidity with alcohol and human immunodeficiency virus (HIV) in HCV-infected individuals. Despite recent improvements in treating HCV infection using pegylated interferon alpha (PEGIFN-alpha) and ribavirin, about half of individuals infected with some genotypes, for example genotypes 1 and 4, will not respond to treatment or cannot be treated because of contraindications. This review will also aim to describe the importance of IFN-alpha-based therapies in HCV infection, ways of monitoring them, and associated complications.

Cooper CL, Cooper CL, MacPherson P, Cameron W. · University of Ottawa, Ottawa, Canada. · Can J Gastroenterol. · Pubmed #16432557 links to  free full text

Abstract: The present review considers issues pertaining to the precision and variability of quantitative hepatitis C virus (HCV) measurement in general, outlines the characteristics of HCV RNA in HIV-HCV coinfection and evaluates those factors which may affect this measure. The clinical relevance of accurate HCV measurement in HIV-HCV coinfection is discussed.

Cooper CL, Cooper CL, MacPherson P, Cameron W. · University of Ottawa, Ottawa, Canada. · Can J Gastroenterol. · Pubmed #16432557 links to  free full text

Abstract: The present review considers issues pertaining to the precision and variability of quantitative hepatitis C virus (HCV) measurement in general, outlines the characteristics of HCV RNA in HIV-HCV coinfection and evaluates those factors which may affect this measure. The clinical relevance of accurate HCV measurement in HIV-HCV coinfection is discussed.

Cooper CL. · Division of Infectious Diseases, The Ottawa Hospital-General Campus, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. · Clin Infect Dis. · Pubmed #16265617 No free full text.

Abstract: Combination antiretroviral therapy reduces overall and liver-specific morbidity and mortality in coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) and represents the most beneficial pharmaceutical treatment intervention for most coinfected patients. Antiviral therapy for HCV infection is potentially organ- and life-saving but, in general, should be reserved for patients who achieve suppression of HIV RNA and immune restoration from combination antiretroviral therapy or for patients with nadir CD4+ T lymphocyte levels of >350 cells/microL. Safe and virologically active treatment of coinfection with HIV and hepatitis B virus can be concurrently achieved by the use of combination antiretroviral therapy regimens containing lamivudine and/or tenofovir.

Cooper CL. · The Ottawa Hospital--General Campus, Room G12, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada. · Expert Rev Anti Infect Ther. · Pubmed #15757459 No free full text.

Abstract: The natural history of chronic viral hepatitis is altered by HIV coinfection. Liver fibrosis rates and clinical features of liver disease develop more rapidly. Although HIV-hepatitis C virus coinfected subjects may progress more rapidly to AIDS, this is probably explained by comorbid illness, substance abuse and socioeconomic circumstances. Safe and virologically active treatment of HIV-hepatitis B virus coinfection can be concurrently achieved by the use of highly active antiretroviral therapy regimens containing lamivudine and/or tenofovir. In most cases, highly active antiretroviral therapy represents the most beneficial initial pharmaceutical intervention for HIV-hepatitisC virus coinfection. HepatitisC virus antiviral therapy should, in most cases, be reserved for those achieving HIV RNA suppression and immune restoration from highly active antiretroviral therapy or with nadir CD4 T-lymphocytes above 350 cells/microl.

Cooper CL. · Division of Infectious Diseases, University of Ottawa, Ottawa Hospital, Room G12-501 Smyth Road, Ottawa, Ontario, Canada. · J Int Assoc Physicians AIDS Care (Chic Ill). · Pubmed #14986516 No free full text.

Abstract: The natural history of hepatitis C virus (HCV) infection is altered by human immunodeficiency virus (HIV) coinfection. Plasma HCV RNA is higher in HIV-infected patients and may further increase as HIV immune deficiency progresses. Hepatic fibrosis and clinical features of hepatic dysfunction develop more rapidly in HIV/HCV coinfection than in HCV alone. Although HIV/HCV-coinfected patients may progress more rapidly to AIDS, other confounding variables include comorbidities, substance abuse, and social issues. Alcohol consumption accelerates both HCV and HIV disease. Given these interactions and the high prevalence of HIV/HCV coinfection, chronic HCV infection will greatly affect the morbidity, mortality, and medical management of HIV patients, and HIV will also affect the care of patients with HCV.

Cooper CL, Cameron DW. · Division of Infectious Diseases, Ottawa Hospital, University of Ottawa, Ottawa, Ontario K1H 8L6, Canada. · Clin Infect Dis. · Pubmed #12228825 No free full text.

Abstract: The effect of anti-human immunodeficiency virus (HIV) treatment on hepatitis C virus (HCV) RNA levels in HIV-HCV-coinfected persons is uncertain. Although it is commonly believed that, with the initiation of HIV treatment, there may be an initial increase followed by a gradual decrease of HCV RNA levels to lower than those at pretreatment, the published studies evaluating this are of small and heterogeneous populations, are limited in follow-up, and have conflicting results. A prospective clinical trial of sufficient size and duration may help clarify this issue. This may be clinically relevant, because lower HCV RNA levels are a predictive factor for favorable response to HCV antiviral therapy.

Cooper CL, Al-Bedwawi S. · University of Ottawa Hospital, Division of Infectious Diseases, The Ottawa Hospital-General Campus, The Ottawa Health Research Institute, Ontario, Canada. · HIV Clin Trials. · Pubmed #17162319 links to  free full text

Abstract: METHOD: Infectious complications were assessed in 25 HIV-HCV coinfected patients receiving 29 courses of HCV therapy (786 person-weeks). RESULTS: The infection rate (1.3 infections/100 person-weeks) was similar when compared to the rate in HIV-negative patients. HIV status and neutrophil nadir did not predict infection risk or rate. CONCLUSION: Interferon dose reduction and/or G-CSF in HCVtreated HIV patients with neutropenia are not justified.

Cooper CL, Davis HL, Angel JB, Morris ML, Elfer SM, Seguin I, Krieg AM, Cameron DW. · Division of Infectious Diseases, University of Ottawa at The Ottawa Hospital, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada. · AIDS. · Pubmed #16135900 No free full text.

Abstract: BACKGROUND: HIV patients are vaccine hyporesponsive. METHODS: We evaluated CPG 7909, a synthetic oligodeoxynucleotide containing immunostimulatory CpG motifs, as an adjuvant to Engerix-B. A randomized, double-blind controlled trial was conducted to determine safety and hepatitis B virus (HBV) immunogenicity in adult HIV subjects on effective antiretroviral therapy. HBV-susceptible subjects, half of whom had failed previous vaccination, were vaccinated at 0, 1 and 2 months with a double dose of Engerix-B with/without (+/-) 1 mg CPG 7909. HBV immune subjects (anti-HBsAg titres > or = 10 mIU/l) received either CPG 7909 alone or saline. Safety, anti-HBs titres and lymphocyte proliferation response (LPR) to HBsAg were assessed over 12 months. RESULTS: Vaccinations with Engerix B +/- CPG 7909 were well tolerated locally and systemically. HIV suppression and CD4 cell counts were maintained. Anti-HBs titers were significantly higher in vaccinees receiving CPG 7909, for all time points after the second dose. Seroprotective titres (> or = 10 mIU/ml) by 6 and 8 weeks, and 12 months were found in 89, 89, and 100% of subjects receiving CPG 7909 compared to 53, 42, and 63% of controls respectively (P = 0.029, 0.005, and 0.008). HBsAg LPR was increased at all time-points up to 12 months after vaccination with addition of CPG 7909 (P < 0.05). CONCLUSIONS: Addition of CPG 7909 achieves rapid, higher, and sustained HBV seroprotection and increases HBV-specific T helper cell response to HBV vaccine in HIV subjects. These results confirm a potential adjuvant role for CPG 7909 in vaccine hyporesponsive populations including those living with HIV.

Cooper CL, Davis HL, Morris ML, Efler SM, Adhami MA, Krieg AM, Cameron DW, Heathcote J. · Division of Infectious Diseases, University of Ottawa at The Ottawa Hospital and Ottawa Health Research Institute, Ottawa, Canada. · J Clin Immunol. · Pubmed #15622454 No free full text.

Abstract: Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN) act as potent Th1-like immune enhancers with many antigens in animal models. We have extended these observations to the first clinical evaluation of the safety, tolerability and immunogenicity of CPG 7909 when added to a commercial HBV vaccine. In a randomized, double-blind phase I dose escalation study, healthy volunteers aged 18-35 years were vaccinated at 0, 4 and 24 weeks by intramuscular injection with Engerix-B (GlaxoSmithKline). The regular adult dose of 20 microg recombinant hepatitis B surface antigen (HBsAg) adsorbed to alum was administered mixed with saline (control) or with CPG 7909 at one of three doses (0.125, 0.5 or 1.0 mg). HBsAg-specific antibody responses (anti-HBs) appeared significantly sooner and were significantly higher at all timepoints up to and including 24 weeks in CPG 7909 recipients compared to control subjects (p< or = 0.001). Strikingly, most CpG 7909-vaccinated subjects developed protective levels of anti-HBs IgG within just two weeks of the priming vaccine dose. A trend towards higher rates of positive cytotoxic T cell lymphocyte responses was noted in the two higher dose groups of CPG 7909 compared to controls. The most frequently reported adverse events were injection site reactions, flu-like symptoms and headache. While these were more frequent in CPG 7909 groups than in the control group (p<0.0001), most were reported to be of mild to moderate intensity regardless of group. In summary, CPG 7909 as an adjuvant to Engerix-B was well-tolerated and enhanced vaccine immunogenicity. CPG 7909 may allow the development of a two-dose prophylactic HBV vaccine.

Siegrist CA, Pihlgren M, Tougne C, Efler SM, Morris ML, AlAdhami MJ, Cameron DW, Cooper CL, Heathcote J, Davis HL, Lambert PH. · Department of Pediatrics, Center for Vaccinology and Neonatal Immunology, University of Geneva, C.M.U., 1 rue Michel-Servet, 1211 Geneva 4, Switzerland. · Vaccine. · Pubmed #15542181 No free full text.

Abstract: We assessed the avidity maturation process elicited by human immunization with alum-adsorbed HBsAg alone or with a novel adjuvant containing CpG motifs (CpG 7909). Mean avidity indexes and distribution of low- and high-avidity anti-HBs indicated that avidity maturation essentially takes place late after priming. CpG 7909 markedly enhanced this affinity maturation process, increasing the pool of high-avidity antibodies. The influence of CpG 7909 was antigen-specific, isotype-specific and distinct from the influence on anti-HBs production, as avidity did not correlate with anti-HBs IgG titers. This is the first demonstration that a novel human adjuvant may induce antibodies with higher antigen-binding affinity.

Cooper CL. · Division of Infectious Diseases, The Ottawa Hospital, Ottawa, Ontario, Canada. · Curr Opin HIV AIDS. · Pubmed #19372929 No free full text.

Abstract: PURPOSE OF REVIEW: This review considers the differential diagnosis, pathophysiology and risk of hepatotoxicity of specific antiretroviral medications. RECENT FINDINGS: Currently prescribed antiretroviral medications are associated with an incidence of grade 3/4 liver enzyme elevation of less than 5%. Clinically apparent hepatotoxicity rates are much lower. The risk of adverse events with combination HIV and hepatitis C virus treatments is low, assuming that several nucleosides including didanosine and stavudine are avoided. SUMMARY: Irrespective of the HIV antiretroviral regimen prescribed, careful observation of liver function and enzymes is advised, especially in those with comorbid liver disease. The majority of patients do not experience treatment-limiting liver toxicities, achieve virological suppression, and realize immunological restoration.

Yoshida EM, Sherman M, Bain VG, Cooper CL, Deschênes M, Marotta PJ, Lee SS, Krajden M, Witt-Sullivan H, Bailey RJ, Usaty C, Peltekian K, Anonymous00035. · University of British Columbia, Vancouver, Canada. · Can J Gastroenterol. · Pubmed #19319382 No free full text.

Abstract: BACKGROUND: Pegylated interferon (pegIFN) and ribavirin combination therapy remains the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the wealth of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegIFN-based therapy is largely unreported. AIM: To assess the effectiveness of the retreatment of patients who have previously failed an initial course of pegIFN-based therapy with pegIFNalpha-2a and ribavirin. METHODS: A post-hoc analysis of a multicentre open-label study was performed. Patients received pegIFNalpha-2a and ribavirin at a dose of 800 mg/day and later 1000 mg/day to 1200 mg/day for 24 to 48 weeks at the discretion of the investigator. Outcomes at week 12 (early virological response [EVR]) and week 24 (sustained virological response [SVR]) were analyzed. RESULTS: Eighty-seven patients who had relapsed after previous pegIFN-based therapy (n=28; 78% genotype 1) or were nonresponders (n=59; 71% genotype 1) were analyzed. Of the relapsers, 86% achieved an EVR and 68% achieved an SVR. In relapsers to pegIFN monotherapy (n=15) or pegIFN plus ribavirin (n=13), 60% and 77% achieved an SVR, respectively. Fibrosis and genotype did not affect the likelihood of SVR in relapsers although this may be the result of the relatively small number of patients. In previous nonresponders, an EVR was achieved in 53% but an SVR occurred in only 17%. In nonresponders to pegIFN monotherapy (n=9) and pegIFN plus ribavirin (n=50), 33% and 14% achieved an SVR, respectively. Genotype did not affect SVR in nonresponders. Only 10% with a METAVIR score of F3 or F4 on liver biopsy achieved an SVR. CONCLUSIONS: Relapse after previous pegIFN-based therapy is associated with a strong probability of treatment success whereas retreatment of those with previous nonresponse does not.

Cooper CL, Mills E, Wabwire BO, Ford N, Olupot-Olupot P. · University of Ottawa Division of Infectious Diseases, Room G12, The Ottawa Hospital-General Campus, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6. · Int J Infect Dis. · Pubmed #19004656 No free full text.

Abstract: There is a heavy burden of HIV-hepatitis B virus (HBV) and HIV-hepatitis C virus (HCV) co-infection in many regions of the developing world. An often unmentioned illness, issues of poverty, socio-economic status, nutrition, access to medical care, and mistrust of Western-style medicine conspire to reduce the opportunity to receive clinical work-up and treatment for chronic viral hepatitis. We discuss key issues specific to the treatment of viral hepatitis and obstacles to success with this endeavor in the context of HIV co-infection in Africa. We predict that provision of viral hepatitis antiviral therapy will become a more pressing issue as more HIV-infected patients receive lifesaving combination antiretroviral therapy only to succumb thereafter from viral hepatitis-induced liver disease. Given the lessons learned from combination antiretroviral rollout in sub-Saharan Africa, establishing expertise and infrastructure for viral hepatitis care and antiviral therapy is relevant. Failure to act now may diminish the milestones and the gains made with antiretroviral therapy in the developing world.

Cooper CL, Bailey RJ, Bain VG, Anderson F, Yoshida EM, Krajden M, Marotta P, Anonymous00013. · University of Ottawa, Ottawa Health Research Institute, The Ottawa Hospital, Ottawa, Ontario. · Can J Gastroenterol. · Pubmed #18701944 links to  free full text

Abstract: BACKGROUND: There is little published information on baseline characteristics and therapeutic outcomes in hepatitis C virus (HCV)-infected Aboriginal Canadians. It is unclear what proportion of HCV-infected Aboriginal people receive therapy relative to other populations. METHODS: Adults with chronic HCV infection, quantifiable serum HCV-RNA levels and compensated liver disease were assigned, at the physician's discretion, to either 24 or 48 weeks of treatment with peginterferon alpha-2a 180 mug/week plus ribavirin at a dose of 800 mg/day, or 1000 mg/day or 1200 mg/day in an open-label, expanded access program. The primary outcome was sustained virological response, defined as undetectable HCV-RNA by qualitative polymerase chain reaction (less than 50 IU/mL) at the end of 24 weeks of untreated follow-up. Baseline characteristics and outcomes in Aboriginal and non-Aboriginal patients were compared. RESULTS: A total of 2614 patients were eligible for the analysis; 44 individuals (1.7%) self-identified as being of Aboriginal heritage. The baseline characteristics of these two groups were similar. An overall sustained virological response was achieved in 47.7% and 46.5% of Aboriginal and non-Aboriginal patients, respectively. The overall frequencies of adverse events and laboratory abnormalities were similar between the two groups, although cytopenias occurred less frequently in Aboriginal patients. INTERPRETATION: Aboriginal patients were greatly under-represented in the present 'community'-based treatment program, yet viral responses were similar to those of a non-Aboriginal cohort. To increase the uptake of HCV therapy in the Aboriginal population, clarification of the obstacles to treatment is warranted.

Angel JB, Cooper CL, Clinch J, Young CD, Chenier A, Parato KG, Lautru M, Davis H, Cameron DW. · Ottawa Health Research Institute, 501 Smyth Rd,, Ottawa, ON, K1H 8L6, Canada. · J Immune Based Ther Vaccines. · Pubmed #18700037 links to  free full text

Abstract: ABSTRACT: BACKGROUND: Lack of adequate adjuvancy is a possible explanation for lack of vaccine immunogenecity. Immunostimulatory CpGs are potent vaccine adjuvants and may be an important component of the development vaccines, particularly those for which a cellular immune response is required for protection. We have previously demonstrated that CpG ODN co-administration with hepatitis B vaccine results in earlier, stronger and more sustained antibody responses to hepatitis B surface antigen in HIV infected individuals, and wished to determine if, in this population, helper T-cell responses were also enhanced. METHODS: We conducted a double-blind, placebo-controlled trial in hepatitis B susceptible, effectively treated HIV-seropositive individuals. Participants received hepatitis B vaccine, with either placebo or CPG 7909 1.0 mg at week 0, 4 and 8. To determine the impact of CpG on cellular immune responses, lymphoproliferative responses (LPR) were evaluated by [3H]-thymidine incorporation at baseline and weeks 4, 8, 12, 24, and 48. Immunophenotyping of lymphocyte subsets was also determined at these time points. RESULTS: Of 36 patients enrolled, 18 received hepatitis B vaccine alone, and 18 received hepatitis B vaccine with CpG. Inclusion of CPG 7909 was associated with a greater proliferative response to HBsAg at all time points following initial vaccination. This increase was statistically significant at 8 weeks (p = 0.042) and 48 weeks (p = 0.024). Similar results were observed when LPR were evaluated as stimulation indices (SI). No differences in proliferative responses to HIV p24 Ag were observed, nor were there any differences in lymphocyte subsets. CONCLUSION: In addition to enhancing humoral responses to vaccination, we describe for the first time that CPG 7909 enhances cellular immunity to vaccine antigen in a typically hyporesponsive population. This adjuvancy may be important in the development of an effective vaccine for which a cellular immune response is required for protection.

Cooper CL, Ahluwalia NK, Efler SM, Vollmer J, Krieg AM, Davis HL. · Coley Pharmaceutical Canada, Ottawa, Canada. · J Immune Based Ther Vaccines. · Pubmed #18541039 links to  free full text

Abstract: ABSTRACT: BACKGROUND: Chronic hepatitis C virus (HCV) infection results from weak or absent T cell responses. Pegylated-interferon-alpha (IFN-alpha) and ribavirin, the standard of care for chronic HCV, have numerous immune effects but are not potent T cell activators. A potent immune activator such as TLR9 agonist CpG oligodeoxynucleotide (CpG) may complement current treatment approaches. METHODS: Peripheral blood mononuclear cells (PBMC) obtained from HCV chronic carriers who failed previous treatment and from healthy donors were incubated in vitro with the three main CpG classes (A, B or C), recombinant IFN-alpha-2b (IntronA) and/or ribavirin. Proliferation and cytokine secretion (IFN-alpha, IL-10 and IP-10) were evaluated. RESULTS: CpG induced proliferation and cytokine secretion in patterns expected for each CpG class with similar group means for HCV and healthy donors. IntronA and ribavirin, alone or together, had no detectable effects. IntronA and C-Class CpG together induced more IFN-alpha than CpG alone in most subjects. IFN-alpha secretion was proportional to the number of plasmacytoid dendritic cells in PBMC from healthy donors but not HCV donors in whom responses were highly heterogeneous. CONCLUSION: The strong immune stimulatory effect of CpG on PBMC isolated from treatment-failed HCV patients suggests possible utility alone or in combination with current HCV antiviral treatment.

Costiniuk CT, Camacho F, Cooper CL. · Department of Internal Medicine, University of Ottawa, Canada. · Clin Infect Dis. · Pubmed #18532889 No free full text.

Abstract: BACKGROUND: Anemia is a complication of therapy for hepatitis C virus (HCV) infection, necessitating dose reductions or therapy abandonment. Administration of an erythropoiesis-stimulating agent (ESA) is a common strategy to manage this complication. Clinical data in other patient populations demonstrate increased rates of cardiovascular events, thrombosis, malignancy, and death among ESA recipients. Event rates in the context of HCV treatment are unknown. METHODS: All recipients of interferon-ribavirin-based HCV therapy at the Ottawa Hospital Viral Hepatitis Clinic from October 2003 through October 2006 were identified. Predictors of ESA use were assessed by regression analysis. Adverse events during and after treatment were evaluated. RESULTS: A total of 174 courses of HCV therapy were initiated. Predictors of ESA use included older age, lower weight, lower baseline hemoglobin level, and infection with HCV genotype 1 or 4. Targeted hemoglobin levels of >110 g/L were achieved in 88% of ESA recipients. Although not statistically significant, sustained virological responses were obtained in more recipients of ESA (54%) than nonrecipients (45%). In the period after HCV treatment, no myocardial infarctions, deep vein thromboses, or pulmonary embolisms occurred; the frequency of stroke and cancer events were low; and rates of adverse events appeared to be similar between groups. CONCLUSIONS: ESA use is not associated with increased risk of cardiovascular events, malignancy, thrombosis, or death in HCV-infected patients during receipt of HCV therapy or in the period after completion. Given the inherent differences in patient populations, practitioners should exercise caution when extrapolating the results of studies of other diseases to HCV infection. Our efficacy and safety analysis suggests against the withholding of ESAs in the management of anemia induced by HCV treatment.

Cooper CL, Angel JB, Seguin I, Davis HL, Cameron DW. · Division of Infectious Diseases, University of Ottawa at Ottawa Hospital, Ottawa Health Research Institute, Ottawa, Canada. · Clin Infect Dis. · Pubmed #18444872 No free full text.

Abstract: BACKGROUND: Human immunodeficiency virus (HIV)-infected persons are hyporesponsive to hepatitis B virus (HBV) vaccination. CPG 7909 is an oligodeoxynucleotide containing immunostimulatory CpG motifs that activate human B and plasmacytoid dendritic cells via Toll-like receptor 9. We previously reported that addition of CPG 7909 to a commercial HBV vaccine enhanced the kinetics, magnitude, and longevity of the seroprotective response over 48 weeks. We now report data for the 5-year period following vaccination. METHODS: A randomized, double-blind, controlled trial was conducted to determine clinical safety and immunogenicity of HBV vaccine in adult HIV-infected subjects receiving effective antiretroviral therapy. HBV-susceptible subjects, one-half of whom had experienced previous vaccination failure, were vaccinated at 0, 1, and 2 months with a double adult dose of recombinant HBV vaccine, with or without 1 mg of CPG 7909 (19 subjects per arm). Titers of antibody to HBV surface antigen (anti-HBs) were measured at 6-month intervals for up to 60 months. RESULTS: The proportion of participants achieving and retaining seroprotection (surface antibody titers, > or =10 mIU/mL) was greater in CPG 7909 recipients (P < .05 at all time points). Geometric mean anti-HBs titers were higher in the CPG 7909 group than in the control group (without CPG 7909 adjuvant) at all measured time points. CONCLUSIONS: The immunostimulatory properties of CPG 7909 present an important strategy in achieving long-term protection in HIV-infected patients and other HBV vaccine-hyporesponsive populations.

Costiniuk CT, Mills E, Cooper CL. · Department of Internal Medicine, University of Ottawa, Ottawa, Canada. · Can J Gastroenterol. · Pubmed #18414712 links to  free full text

Abstract: OBJECTIVES: The systemic and cognitive side effects of hepatitis C virus (HCV) therapy may be incapacitating, necessitating dose reductions or abandonment of therapy. Oral cannabinoid-containing medications (OCs) ameliorate chemotherapy-induced nausea and vomiting, as well as AIDS wasting syndrome. The efficacy of OCs in managing HCV treatment-related side effects is unknown. METHODS: All patients who initiated interferon-ribavirin therapy at The Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario) between August 2003 and January 2007 were identified using a computerized clinical database. The baseline characteristics of OC recipients were compared with those of nonrecipients. The treatment-related side effect response to OC was assessed by c2 analysis. The key therapeutic outcomes related to weight, interferon dose reduction and treatment outcomes were assessed by Student's t test and c2 analysis. RESULTS: Twenty-five of 191 patients (13%) initiated OC use. Recipients had similar characteristics to nonrecipients, aside from prior marijuana smoking history (24% versus 10%, respectively; P=0.04). The median time to OC initiation was seven weeks. The most common indications for initiation of OC were anorexia (72%) and nausea (32%). Sixty-four per cent of all patients who received OC experienced subjective improvement in symptoms. The median weight loss before OC initiation was 4.5 kg. A trend toward greater median weight loss was noted at week 4 in patients eventually initiating OC use (-1.4 kg), compared with those who did not (-1.0 kg). Weight loss stabilized one month after OC initiation (median 0.5 kg additional loss). Interferon dose reductions were rare and did not differ by OC use (8% of OC recipients versus 5% of nonrecipients). The proportions of patients completing a full course of HCV therapy and achieving a sustained virological response were greater in OC recipients. CONCLUSIONS: The present retrospective cohort analysis found that OC use is often effective in managing HCV treatment-related symptoms that contribute to weight loss, and may stabilize weight decline once initiated.

Cooper CL, Badley AD, Angel JB. · Division of Infectious Diseases, Ottawa Hospital General Campus, Ottawa, Ontario; · Can J Infect Dis. · Pubmed #18159334 links to  free full text

Abstract: Knowledge pertaining to hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection is currently incomplete or conflicting. Several points are well studied, however. Plasma HCV RNA levels are higher in matched HIV-infected people than in HIV-seronegative control subjects and are inversely correlated with CD4(+) T lymphocyte counts. HCV genotype does not appear to influence this value. Co-infected individuals develop histological and clinical features of HCV liver disease more rapidly than HIV-seronegative patients. Co-infected individuals appear to respond to interferon-alpha therapy equally as well as HIV-seronegative HCV-infected adults, but minimal information exists regarding the efficacy and toxicity of combination HCV therapy (interferon-alpha plus ribavirin) in this population. Adverse consequences of highly active antiretroviral therapy in co-infected patients include hepatic toxicity and, in a minority of patients, an 'immune restoration syndrome'. It is unclear whether long term, highly active antiretroviral therapy positively or negatively influences the natural history of HCV infection.

Balfour L, Kowal J, Tasca GA, Cooper CL, Angel JB, Macpherson PA, Garber G, Béïque L, Cameron DW. · Division of Infectious Diseases, Ottawa Hospital-General Campus, Ottawa, Ontario, Canada. · AIDS Care. · Pubmed #18058398 No free full text.

Abstract: Accurate treatment knowledge is required for patients to successfully manage complex medical conditions. Existing HIV knowledge scales focus on disease transmission and risk factors. This is the first study to develop and validate a scale to measure HIV treatment knowledge about complex treatment issues such as adherence, side-effects and drug resistance. A total of 346 participants were recruited into this cross-sectional study. Participants included HIV-positive patients (n=130), HIV-hepatitis C co-infected patients (n=22), hepatitis C patients, (n=78), community healthcare providers (n=35) and college students (n=81). Participants completed the proposed HIV Treatment Knowledge Scale and a validated measure of general knowledge about HIV transmission and risk factors. Two-week test-retest data were collected. Results demonstrated that the HIV Treatment Knowledge Scale was significantly correlated with general HIV knowledge across all samples. Among HIV-positive patients, the HIV Treatment Knowledge Scale was positively associated with time since HIV diagnosis. HAART-experienced patients had significantly higher treatment knowledge than HAART-naïve patients. HIV-positive patients scored significantly higher than hepatitis C patients and college students on HIV treatment knowledge. Test-retest reliability (r=0.83) and internal consistency (reliability coefficient=0.90) were both satisfactory. The HIV Treatment Knowledge Scale is a novel, easy-to-administer measure demonstrating high levels of validity and reliability. It has important applications as a clinical teaching tool with patients and healthcare workers and it could be used as an outcome indicator in HIV educational intervention studies.