Kathleen Rollet

HIV and hepatitis C virus coinfection in Canada: challenges and opportunities for reducing preventable morbidity and mortality

Hepatitis C virus (HCV) has emerged as an important health problem in the era of effective HIV treatment. However, very few data exist on the health status and disease burden of HIV/HCV‐coinfected Canadians.

Marijuana Smoking Does Not Accelerate Progression of Liver Disease in HIV–Hepatitis C Coinfection: A Longitudinal Cohort Analysis

In a large human immunodeficiency virus–hepatitis C virus coinfection cohort, we found no evidence that marijuana smoking accelerated progression to significant liver fibrosis, cirrhosis, or end-stage liver disease. Previous studies reporting an association may have been biased by reverse causation due to self-medication.

Factors Associated With Discordance Between Absolute CD4 Cell Count and CD4 Cell Percentage in Patients Coinfected With HIV and Hepatitis C Virus

BACKGROUND Liver cirrhosis has been associated with decreased absolute CD4 cell counts but preserved CD4 cell percentage in human immunodeficiency virus (HIV)-negative persons. We evaluated factors associated with discordance between the absolute CD4 cell count and the CD4 cell percentage in a cohort of patients coinfected with HIV and hepatitis C virus (HCV). METHODS Baseline data from 908 participants in a prospective, Canadian, multisite cohort of individuals with HIV-HCV coinfection were analyzed. Absolute CD4 cell count and CD4 cell percentage relationships were evaluated. We defined low and high discordance between absolute CD4 cell count/CD4 cell percentage relationships as CD4 cell percentages that differed from the expected CD4 cell percentage, given the observed absolute CD4 cell count, by ±7 percentage points; we defined very low and very high discordance as differences of ±14 percentage points. Factors associated with high or very high discordance, including either end-stage liver disease or aspartate transaminase to platelet ratio index (APRI) of >1.5, were analyzed using multivariate logistic regression models and compared to groups with concordant and low discordant results. RESULTS High/very high discordance was seen in 31% (n = 286), while 35% (n = 321) had concordant values. Factors associated with very high discordance at baseline included history of end-stage liver disease (adjusted odds ratio [aOR], 6.52; 95% confidence interval [CI], 2.27-18.67) and APRI of >1.5 (aOR 4.69; 95% CI, 1.64-13.35). Compared with those with detectable HCV RNA, those who cleared HCV spontaneously were less likely to have very high discordance. CONCLUSIONS Discordance between absolute CD4 cell count and CD4 cell percentage is common in an HIV/HCV-coinfected population and is associated with advanced liver disease and ongoing HCV replication.

Insulin resistance is associated with progression to hepatic fibrosis in a cohort of HIV/hepatitis C virus-coinfected patients.

Objective:Hepatitis C virus (HCV) infection is associated with higher insulin levels and insulin resistance. We evaluated factors associated with insulin resistance in a cohort of HIV/HCV-coinfected patients and determined the effect of insulin resistance on the development of hepatic fibrosis. Methods:Data were analysed from 158 nondiabetic participants in a prospective Canadian cohort of HIV/HCV-coinfected patients. Patients were defined as having insulin resistance using the homeostasis model for assessment of insulin resistance (HOMA-IR) index. Factors associated with a high index (HOMA-IR ≥2) were identified using multivariate logistic regression. Incidence rates of liver fibrosis [aspartate aminotransferase-to-platelet ratio index (APRI) ≥1.5] were calculated, and multivariate time-dependent Cox regression models used to assess the effect of baseline insulin resistance on the risk of developing an APRI score of at least 1.5 during follow-up. Results:Overall, 56% had baseline HOMA-IR of at least 2. In the adjusted multivariate logistic analysis, only baseline BMI of more than 25 kg/m2 remained associated with insulin resistance [adjusted odds ratio 3.66, 95% confidence interval (CI) 1.70–7.92]. Rates of progression to significant hepatic fibrosis (APRI ≥1.5) were higher in those with HOMA-IR of at least 2 (16.32 per 100 person-years, 95% CI 6.68–25.97) compared with those with HOMA-IR less than 2 (7.95 per 100 person-years, 95% CI 0.16–15.75). Baseline HOMA-IR of at least 2 was associated with the development of significant fibrosis (adjusted hazard ratio 7.71, 95% CI 2.55–23.36). Conclusion:In this first longitudinal analysis, insulin resistance was very common among coinfected patients and was associated with modifiable risk factors such as elevated BMI. Insulin resistance was found to be strongly associated with progression to hepatic fibrosis over time.

Correlates of drug use cessation among participants in the Canadian HIV–HCV Co-infection Cohort

BACKGROUND Ongoing drug use remains a barrier to HIV and HCV treatment. We examined the occurrence and correlates of drug use cessation among HIV-HCV co-infected drug users participating in HIV care. METHODS Participants from the Canadian Co-infection Cohort reporting drug use (injecting drugs and/or smoking crack) with at least two follow-up visits were included (n=521 (43%), 1832 visits). Socio-demographics, behavioural, and health information were collected at each six-month visit. Associations with cessation (no drug use since last visit) were examined using non-linear mixed effects logistic regression models with random intercepts. RESULTS During follow-up, 361 (69%) participants ceased using drugs. Having a fixed address (aOR [adjusted odds ratio] 1.73, CI [95% confidence interval] 1.02-2.96) and smoking crack without injecting drugs (aOR 3.10, CI 2.05-4.71) were positively associated. Living alone (aOR 0.47, CI 0.35-0.63), current tobacco use (aOR 0.41, CI 0.26-0.64), hazardous alcohol drinking (aOR 0.67, CI 0.49-0.91), snorting drugs (aOR 0.52, CI 0.37-0.74), having a greater exposure to addiction programmes (aOR 0.88, CI 0.81-0.94), having been recruited in Quebec or Nova Scotia (aOR 0.41, CI 0.25-0.66), and British Columbia or Alberta (aOR 0.51, CI 0.32-0.82) were negatively associated. Various socio-demographic (age, education) and health-related (HIV duration, care adherence) factors were not associated. CONCLUSION Drug use cessation among HIV-HCV co-infected persons is relatively common in this cohort. Stable housing and supportive living situations seem to be important facilitators for drug use cessation in this population. Greater efforts should be made to retain patients in addiction treatment programmes.

Who needs direct-acting antivirals for HCV? Challenges faced in advancing HCV therapy for HIV-HCV-coinfected individuals.

BACKGROUND The recent availability of new direct-acting antivirals (DAAs) for HCV treatment, which significantly increase sustained virological response rates for genotype 1 HCV infection, has brought new optimism with respect to curative HCV treatment for HIV-HCV-coinfected patients. We describe the characteristics of coinfected patients who could be eligible for DAAs to determine potential challenges facing clinicians and patients hoping to take advantage of these new therapies. METHODS We evaluated the sociodemographic and clinical characteristics of the genotype 1 HCV-HIV-infected participants in a Canadian prospective multicentre cohort study at their most recent visit to assess potential eligibility for combination HCV treatment with boceprevir or telaprevir. RESULTS Of the 1,020 coinfected participants enrolled in the cohort, 707 (85%) had evidence of chronic HCV infection (HCV-RNA-positive), of whom 497 (70%) were infected with genotype 1; 375 (75%) were naive to HCV treatment and 122 (25%) had previously received therapy and failed. Only 143 (38%) of HCV treatment-naive and 39 (32%) of treatment-experienced participants had no absolute contraindications for treatment. Alcohol abuse, active depression and decompensated liver disease were the most frequent reasons for treatment ineligibility. The majority would require alterations in antiretroviral regimens to avoid important drug-drug interactions. CONCLUSIONS Although the need for curative HCV therapy in HIV-HCV coinfection is great, the actual number of patients who could be eligible for DAAs at the present time may be quite low. There remains an urgent need to develop safe, simple and interferon-sparing treatments for coinfected individuals.

Ability of a rapid HIV testing site to attract and test vulnerable populations: a cross-sectional study on Actuel sur Rue:

Quebec’s HIV epidemic persists, particularly among men who have sex with men (MSM) and in Montreal. Increasing access to HIV testing is necessary and community-based rapid testing offers one strategy. This paper examines the clienteles and activities of a rapid HIV testing site in Montreal, the pilot project Actuel sur Rue. Comparative analyses were conducted with 1357 MSM, 147 heterosexual men and 64 women who visited Actuel sur Rue between July 2012 and November 2013 on socio-demographics, health, drug use, sexual practices/infection and HIV testing/prevention. Significant group differences were observed in each category. Actuel sur Rue received 1901 clients, conducted 1417 rapid HIV tests and tested 77 never-tested individuals. Rapid testing produced a high reactive rate (2%). Only 1/28 of those with reactive tests had no previous HIV testing, and 36% had used post-exposure prophylaxis, suggesting missed opportunities for prevention. Findings highlight diverse client vulnerability profiles and the relevance of checkpoints and further prevention efforts.

Liver fibrosis is strongly associated with an enhanced level of immunosuppressive tryptophan catabolism independently of HCV viremia in ART-treated HIV/HCV co-infected patients

Background HCV infection induces hepatic and extra-hepatic damage that includes kidney and neurocognitive dysfunction. Tryptophan (Trp) is catabolized into immunosuppressive kynurenine (Kyn) by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3 dioxegenase (TDO). Increased Trp catabolism measured by Kyn/Trp ratio has been associated with neurocognitive impairment and immune dysfunction in HIV mono-infection. Here, we assessed the contribution of Trp catabolism in HCV/HIV co-infected patients.

Influence of Hepatitis C Virus Sustained Virological Response on Immunosuppressive Tryptophan Catabolism in ART-Treated HIV/HCV Coinfected Patients

Background:We previously reported an association between tryptophan (Trp) catabolism and immune dysfunction in HIV monoinfection. Coinfection with HIV is associated with more rapid evolution of hepatitis C virus (HCV)–associated liver disease despite antiretroviral therapy (ART), possibly due to immune dysregulation. We hypothesized that liver fibrosis in HIV/HCV coinfection would be associated with immune dysfunction and alterations in Trp metabolism. Methods:Trp catabolism and inflammatory soluble markers were assessed in plasma samples from ART-treated HIV/HCV-coinfected patients (n = 90) compared with ART-treated HIV-monoinfected patients and noninfected subjects. Furthermore, 17 additional coinfected patients with sustained virological response (SVR) were assessed longitudinally 6 months after completion of interferon-&agr;/ribavirin treatment. Results:HIV/HCV patients had higher Trp catabolism compared with HIV-monoinfected and healthy individuals. Elevated kynurenine levels in HIV/HCV patients with liver fibrosis correlated with the prognostic aspartate aminotransaminase to platelet ratio (APRI scores) and insulin levels. Furthermore, HIV/HCV patients had elevated levels of disease progression markers interleukin-6 and induced protein 10 and shared similar levels of markers of microbial translocation (intestinal fatty acid-binding protein, soluble CD14 and lipopolysaccharide-binding protein) compared with HIV-monoinfected and healthy individuals. Successful HCV treatment improved APRI score and markers of disease progression and microbial translocation although elevated Trp catabolism remained unchanged 6 months after SVR. Conclusion:ART-treated HIV/HCV-coinfected patients had elevated immunosuppressive Trp catabolism when compared with monoinfected HIV-treated patients, which did not normalize after SVR. These findings suggest that a necroinflammatory liver syndrome persists through inflammation by Trp catabolism after 6 month of SVR.

Missed Opportunities for Hepatocellular Carcinoma Screening in an HIV/Hepatitis C Virus–Coinfected Cohort

We examined adherence to guidelines for screening of hepatocellular carcinoma in a cohort of HIV/hepatitis C virus-coinfected patients. Thirty-six percent of patients with documented cirrhosis did not have a screening ultrasound. Patients at centers with standardized systems for screening were more likely to have had an ultrasound performed.