Mortality in HIV‐infected injection drug users with active vs cleared hepatitis C virus‐infection: a population‐based cohort study

Summary. Acute hepatitis C virus (HCV) infection may lead to chronic HCV‐infection with detectable HCV RNA or to spontaneous clearance with no HCV RNA, but detectable HCV antibodies. It is unknown whether HCV RNA status is associated with mortality in HIV‐infected injection drug users (IDUs). We conducted a nationwide population‐based cohort study to examine the impact of HCV RNA status on overall and cause‐specific mortality in HIV‐infected IDUs. We computed cumulative mortality and used Cox Regression to estimate mortality rate ratios (MRR). We identified 392 HIV‐infected patients of whom 284 (72%) had chronic HCV‐infection (HCV RNA positive patients) and 108 (28%) had cleared the HCV‐infection (HCV RNA negative patients). During 1286 person‐years of observation (PYR), 157 persons died (MR = 122/1000 PYR, 95% CI: 104–143). The estimated 5‐year probabilities of survival were 0.58 (95% CI: 0.51–0.65) in the chronically HCV‐infected and 0.52 (95% CI: 0.40–0.63) in the cleared HCV group. Chronic HCV‐infection was not associated with overall mortality: MRR 0.85, 95% CI: 0.59–1.21. In HIV‐infected Danish IDUs, chronic HCV‐infection is not associated with increased mortality compared to patients who have cleared the infection.     

Liver transplantation for HIV/hepatitis C virus co‐infected patients

Since the introduction of antiretroviral therapy (ART) in the mid‐1990s, AIDS‐related death has been dramatically reduced, and hepatitis‐C‐virus (HCV)‐related liver failure or hepatocellular carcinoma has currently become the leading cause of death in HIV/HCV co‐infected patients. Liver transplantation may be one of the treatments of choices in such cases, but the indications for transplantation, perioperative management including both HIV and HCV treatments, immunosuppression and the prevention/treatment of infectious complications are all still topics of debate. With the improved understanding of the viral behaviors of both HIV and HCV and the development of novel strategies, especially to avoid drug interactions between ART and immunosuppression, liver transplantation has become a realistic treatment for HIV/HCV co‐infected patients.     

Reduced healthcare utilization following successful hepatitis C virus treatment in HIV‐co‐infected patients with mild liver disease

New direct‐acting antivirals (DAA) for hepatitis C virus (HCV) infection have achieved high cure rates in many patient groups previously considered difficult‐to‐treat, including those HIV/HCV co‐infected. The high price of these medications is likely to limit access to treatment, at least in the short term. Early treatment priority is likely to be given to those with advanced disease, but a more detailed understanding of the potential benefits in treating those with mild disease is needed. We hypothesized that successful HCV treatment within a co‐infected population with mild liver disease would lead to a reduction in the use and costs of healthcare services in the 5 years following treatment completion. We performed a retrospective cohort study of HIV/HCV‐co‐infected patients without evidence of fibrosis/cirrhosis who received a course of HCV therapy between 2004 and 2013. Detailed analysis of healthcare utilization up to 5 years following treatment for each patient using clinical and electronic records was used to estimate healthcare costs. Sixty‐three patients were investigated, of whom 48 of 63 (76.2%) achieved sustained virological response 12 weeks following completion of therapy (SVR12). Individuals achieving SVR12 incurred lower health utilization costs (£5000 per‐patient) compared to (£10 775 per‐patient) non‐SVR patients in the 5 years after treatment. Healthcare utilization rates and costs in the immediate 5 years following treatment were significantly higher in co‐infected patients with mild disease that failed to achieve SVR12. These data suggest additional value to achieving cure beyond the prevention of complications of disease.     

Acute hepatitis C infection in HIV‐negative men who have sex with men

Acute hepatitis C infection is recognized in HIV‐infected men who have sex with men (MSM), but the risk in HIV‐negative MSM remains unclear. We evaluated a population of MSM with acute hepatitis C. From January 2010 to May 2014, all cases of HCV antibody positive HIV‐negative MSM were identified. European AIDS Network criteria were applied to determine acute infection, and 44 individuals fulfilled the criteria for acute hepatitis C. Ten were RNA negative at baseline and classed as prior spontaneous clearance. 15 (34.1%) had a previously negative HCV antibody within 1 year. 11 (25.0%) had significant elevation in ALT levels, and 18 (40.9%) were clinically diagnosed from risk exposure and history. Median age was 37 years (range 24–75). 41 (93.2%) individuals reported unprotected anal sex, 36 with (87.8%) both insertive and receptive intercourse, 4 (9.8%) with receptive intercourse, 1 (2.4%) with insertive intercourse, and no data were recorded for 3 (7.3%) patients. Individuals had an average of 7.3 reported (median 2, range 1–100) partners. 12 (27.3%) engaged in group sex, 11 (25.0%) practised fisting, 11 (25.0%) admitted using drugs during sexual activity, 16 (36.4%) reported nasal, and 9 (20.5%) reported injection drug use. 14 (31.8)% had unprotected sex whilst under the influence of recreational drugs. 29 individuals were aware of a partner's status. 2 (4.5%) individuals had sexual contact with a known HCV monoinfected partner, 13 (29.5%) with a HIV monoinfected partner and 6 (13.6%) with a HCV/HIV coinfected partner. 9 (20.5%) reported a partner/partners with no known infection. No data were available in 14 (31.8%) individuals. 13 (29.5%) individuals had a coexisting STI at the time of acute HCV diagnosis. 8 (18.2%) received HIV postexposure prophylaxis (PEP) within the 6 months prior to the HCV diagnosis (2 were participants in a HIV pre‐exposure prophylaxis trial). 15 (34.1%) individuals achieved spontaneous clearance of HCV, and 11 patients received HCV treatment. Similar to the ongoing epidemic of acute HCV infection in HIV+ MSM, HIV‐negative MSM remain at risk.     

Serological markers of autoimmunity in patients infected with hepatitis C virus: impact of HIV co-infection

OBJECTIVES: We sought to evaluate the prevalence, predictors and significance of autoantibody expression in patients with chronic hepatitis C (CHC) with or without HIV co-infection. METHODS: Retrospective review of laboratory and histologic data for all patients with CHC who had a liver biopsy available. HIV status was documented in all patients. Results analyzed in SPSS10, Chicago, IL, a p value <0.05 was considered significant. RESULTS: 170 patients with hepatitis C viremia, including 107 (63%) HIV co-infection, who had testing for anti-nuclear antibody (ANA) or anti-smooth muscle antibody (ASMA) and anti-mitochondrial antibody (AMA) were included in the study. Overall, 63% (74/117) of patients were ASMA seropositive and 6% (9/153) were positive for ANA. All 117 patients tested for AMA were negative. HIV co-infected patients were significantly more likely to be ASMA positive 71% (53/75) compared to those with hepatitis C alone (50%) [P=0.026]. There were no significant differences in age, gender, race, risk group, alanine aminotransferase (ALT) levels or grade of inflammation on histology between autoantibody positive and negative patients. ASMA positive patients had significantly higher globulin levels (P=0.036) and a trend towards more bridging fibrosis or cirrhosis. Patients with autoantibody expression rarely had histologic features of AIH. CONCLUSION: We found a high rate of ASMA seropositivity in our cohort of patients with chronic hepatitis C, and HIV co-infection was associated with significantly higher rates of ASMA expression. Autoantibody expression was not associated with demographic or clinical characteristics and does not necessarily preclude antiviral therapy.     

Contribution of alcohol use in HIV/hepatitis C virus co-infection to all-cause and cause-specific mortality: A collaboration of cohort studies

Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001–2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1–20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0 g/day, 0.1–20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08–1.29) for 0.0 g/day and 1.84 (1.62–2.09) for >20.0 g/day compared with 0.1–20.0 g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86–1.17) for 0.0 g/day and 1.64 (1.33–2.02) for >20.0 g/day compared with 0.1–20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.     

Factors associated with isolated anti‐hepatitis B core antibody in HIV‐positive patients: impact of compromised immunity

Summary. In regions that are hyperendemic for chronic hepatitis B virus (HBV) infection, prevalence of and risk factors associated with isolated anti‐hepatitis B core antibody (anti‐HBc) in HIV‐positive patients are less well described. HIV‐positive patients who were tested for hepatitis B surface antigen (HBsAg), anti‐hepatitis B surface antibody (anti‐HBs) and anti‐HBc at designated hospitals for HIV care in Taiwan were included for analysis. HBV DNA was detected by real‐time polymerase chain reaction in patients with and without isolated anti‐HBc. Of 2351 HIV‐positive patients, 450 (19.1%) were HBsAg positive, 411 (17.5%) were anti‐HBc positive alone and 963 (41.0%) for both anti‐HBs and anti‐HBc. Compared with patients who were positive for both anti‐HBs and anti‐HBc, patients with isolated anti‐HBc were older, less likely to have anti‐hepatitis C virus antibody (anti‐HCV), had lower CD4 lymphocyte counts and higher plasma HIV RNA loads. Older age (adjusted odds ratio, 1.029; 95% confidence interval, 1.015–1.043) and CD4 <100 cells/μL (adjusted odds ratio, 1.524; 95% confidence interval, 1.025–2.265) were independently associated with isolated anti‐HBc by logistic regression, while presence of anti‐HCV and injecting drug use were not. HBV DNA was detectable in 8.3% of 277 patients with isolated anti‐HBc and 14.3% of 56 patients with both anti‐HBs and anti‐HBc (P = 0.160). In a country hyperendemic for HBV infection, HIV‐positive patients at older age and with CD4 <100 cells/μL were more likely to have isolated anti‐HBc, suggesting that compromised immunity plays a role in the presence of this marker.     

Visits to primary care physicians among persons who inject drugs at high risk of hepatitis C virus infection: room for improvement

The role of primary care physicians (PCP) in hepatitis C virus (HCV) prevention is increasingly emphasized. Yet, little is known about the patterns of contacts with PCP among persons who inject drugs (PWID). We sought to assess the 6‐month prevalence of PCP visiting among PWID at risk of HCV infection and to explore the associated factors. Baseline data were collected from HCV‐seronegative PWID recruited in HEPCO, an observational Hepatitis Cohort study (2004–2011) in Montreal, Canada. An interviewer‐administered questionnaire elicited information on socio‐demographic factors, drug use patterns and healthcare services utilization. Blood samples were tested for HCV antibodies. Using the Gelberg‐Andersen Behavioral Model, hierarchical logistic regression analyses were conducted to identify predisposing, need and enabling factors associated with PCP visiting. Of the 349 participants (mean age = 34; 80.8% male), 32.1% reported visiting a PCP. In the multivariate model, among predisposing factors, male gender [adjusted odds ratio (AOR) = 0.45 (0.25–0.83)], chronic homelessness [AOR = 0.08 (0.01–0.67)], cocaine injection [AOR = 0.46 (0.28–0.76)] and reporting greater illegal or semi‐legal income [AOR = 0.48 (0.27–0.85)] were negatively associated with PCP visits. Markers of need were not associated with the outcome. Among enabling factors, contact with street nurses [AOR = 3.86 (1.49–9.90)] and food banks [AOR = 2.01 (1.20–3.37)] was positively associated with PCP visiting. Only one third of participating PWID reported a recent visit to a PCP. While a host of predisposing factors seems to hamper timely contacts with PCP among high‐risk PWID, community‐based support services may play an important role in initiating dialogue with primary healthcare services in this population.     

Peginterferon‐alfa mono‐therapy in the treatment of acute hepatitis C in HIV‐infection

The ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal treatment outcome in HIV co‐infected individuals. Cohort study of 105 HIV‐infected patients with AHC infection from five centres in two European countries was carried out. Choice of treatment with pegIFN‐alfa alone (group 1; n = 36) or pegIFN‐alfa and ribavirin (RBV) (group 2; n = 69) was at the discretion of the investigator. Outcome was evaluated as RVR and SVR. Fisher's exact and Mann Whitney U tests were used for statistical analysis. All patients were male, median age was 39 years, main route of transmission MSM (91%). In 69% of patients, clinical signs of acute hepatic infection were missing, dominant HCV genotypes were 1 (64%) and 4 (16%) and mean baseline HCV‐RNA was 3.559.085 IU/mL. 60% received HAART and CD4 cell count was 469/mm³. Overall SVR rate was 64.8% (68/105). SVR was reached in 69% of treated patients in group 1 and in 63% of treated patients in group 2 (P = 0.67) while RVR was seen in 61% and 49%, respectively (P = 0.35). Interestingly, by univariate analysis, SVR rates in group 1 were significantly higher in patients initiating therapy within 4 weeks of AHC diagnosis compared to patients initiating therapy within 5–36 weeks after diagnosis (P = 0.03). PegIFN‐alfa alone or in combination with ribavirin results in similar response rates in HIV‐infected patients with AHC. In particular, when treatment is initiated within 4 weeks of diagnosis, pegIFN mono‐therapy might be sufficient to allow for an optimal treatment response.     

Risk behaviours of homeless people who inject drugs during an outbreak of hepatitis C,Northern Ireland, 2016‐2017

From July to August 2016, 4 homeless people who injected drugs (PWID) with acute or recent hepatitis C virus (HCV) infection were reported in Belfast. A multidisciplinary team including public health, homeless and addiction services undertook an investigation to identify risk behaviours and interrupt transmission chains. Recent HCV cases were defined as negative test within the previous year, or reported injecting for less than 1 year; acute cases had tested negative within the previous 6 months. Contacts in the injecting networks of cases were identified for testing. We undertook a cross‐sectional survey using structured questionnaires to elicit risk behaviours for PWID and compare behaviours between self‐reported hepatitis C positive and negative subjects. During the outbreak investigation until December 2017, 156 PWID were tested and 45 (29%) cases identified, including 7 (16%) recent and 13 (29%) acute infections. 68 PWID, including 12 cases, were interviewed. All respondents reported using heroin, with 76% injecting once or more daily. Sharing was reported for spoons (58%) and filters (53%), but also needles (27%) and syringes (29%). Hepatitis C positive individuals had higher odds to be injecting in public toilets (AOR 17, 95% CI 0.71‐400, P < .05) when compared with hepatitis C negative individuals. Hepatitis C positive individuals were more likely to inject in public spaces, but all respondents indicated concerning risk behaviours. We recommend active surveillance with ongoing testing, expanding existing harm reduction programmes and access to bespoke services.     

Alcohol use and non‐adherence to antiretroviral therapy in HIV‐infected patients in West Africa

Aim To investigate the association between alcohol use and adherence to highly active antiretroviral treatment (HAART) among human immunodeficiency virus (HIV)‐infected patients in subSaharan Africa. Design and setting Cross‐sectional survey conducted in eight adult HIV treatment centres from Benin, Côte d'Ivoire and Mali. Participants and measurements During a 4‐week period, health workers administered the Alcohol Use Disorders Identification Test to HAART‐treated patients and assessed treatment adherence using the AIDS Clinical Trials Group follow‐up questionnaire. Findings A total of 2920 patients were enrolled with a median age of 38 years [interquartile range (IQR) 32–45 years] and a median duration on HAART of 3 years (IQR 1–4 years). Overall, 91.8% of patients were identified as adherent to HAART. Non‐adherence was associated with current drinking [odds ratio (OR) 1.4; 95% confidence interval (CI) 1.1–2.0], hazardous drinking (OR 4.7; 95% CI 2.6–8.6) and was associated inversely with a history of counselling on adherence (OR 0.7; 95% CI 0.5–0.9). Conclusions Alcohol consumption and hazardous drinking is associated with non‐adherence to HAART among HIV‐infected patients from West Africa. Adult HIV care programmes should integrate programmes to reduce hazardous and harmful drinking.     

Hepatitis C infection and other drug‐related harms among inpatients who injected drugs in Turkey

Hepatitis C virus (HCV) is easily spread among those who share drug injection equipment. Due to the ease of contraction and growing prevalence of HCV in Eastern Europe, the aims of this study focused on describing risky injection practices as well as the prevalence of HCV, HIV and hepatitis B virus (HBV) among people who inject drugs (PWID) who were admitted to public and private drug treatment centres in Turkey from 2012 to 2013. Other aims included identifying correlates of needle sharing and HCV infection. Of the 4694 inpatients who ever injected drugs and the 3914 who injected in the past 30 days, nearly all (98%) reported heroin as their drug of choice, the vast majority reported ever sharing a needle (73.4% and 79.3%), and the mean age at first injection was 23 years. Of current PWID, 51.9% were HCV‐positive, 5.9% were HBV‐positive and only 0.34% of lifetime PWID were HIV‐positive. Predictors of increased needle sharing include younger age, being unemployed, having lesser education and reporting heroin as a drug of choice. Significant predictors of HCV infection included being 40 years or older, receiving treatment in the Mediterranean region of Turkey, reporting heroin as a primary substance, a longer duration of drug use and sharing needles. With this information, it is essential to improve access to clean injection equipment in Turkey, to focus on improving education on clean injection practices and to enhance efforts in testing and treating HCV‐positive PWID.     

Network‐based recruitment of people who inject drugs for hepatitis C testing and linkage to care

Although oral direct‐acting agent (DAA) therapies have the potential to reduce the burden of hepatitis C virus (HCV) infection, treatment uptake remains low, particularly among people who inject drugs (PWID). This study examined the feasibility of an innovative peer‐based recruitment strategy to engage PWID in HCV testing and treatment. We interviewed an initial set of HCV antibody‐positive PWID as ‘primary indexes’ to gather demographic, drug use, health information and drug network characteristics. Primary indexes were then briefly educated on HCV and its treatment and encouraged to recruit their injection drug ‘network members’ for HCV testing and linkage to care. Eligible network members were enrolled as ‘secondary indexes’ and completed the same index study procedures. In sum, 17 of 36 primary indexes initiated the recruitment of 64 network members who were HCV antibody positive and eligible to become indexes. In multivariable analysis, successful recruitment of at least one network member was positively associated with prior HCV treatment (OR 2.80; CI [1.01, 7.72]), daily or more injection drug use (OR 2.38; CI [1.04, 5.47]), and a higher number of injection drug network members (OR 1.20; CI [1.01, 1.42]). Among the 69 participants with chronic HCV not previously linked to HCV care at enrolment, 91% (n = 63) completed a linkage to HCV care appointment, 45% (n = 31) scheduled an appointment with an HCV provider, and 20% (n = 14) initiated HCV therapy. These findings suggest a potential benefit for peer‐driven, network‐based interventions focused on HCV treatment‐experienced PWID as a mechanism to increase HCV linkage to care.     

Impact of hepatitis C virus infection on all‐cause and liver‐related mortality in a large community‐based cohort of inner city residents

Summary. The aim of this study was to measure the impact of hepatitis C virus (HCV) infection on mortality in a cohort of inner city residents. The Community Health and Safety Evaluation is a community‐based study of inner city residents followed retrospectively and prospectively through linkages with provincial virology and mortality databases. We identified participants having received HCV antibody testing, evaluated cause‐specific mortality rates and factors associated with all‐cause and liver‐related mortality using Cox Proportional Hazards models. Overall, 2332 participants received HCV antibody testing (recent non‐injection drug use – 81%). The prevalence of HCV and HIV was 64% (1495 of 2332) and 21% (485 of 2332), respectively. Between January 2003 and December 2007, there were 180 deaths (192 per 10 000 person‐years; 95% CI: 165, 222), with 21% HIV‐related, 20% drug‐related and 7% liver‐related. Mortality was associated with age >50 [adjusted hazard ratio (AHR) 2.80 vs <40 years (referent group); 95% CI 1.93, 4.07, P < 0.001] and HIV infection (AHR 3.81; 95% CI 2.72, 5.34, P < 0.001), but not positive HCV antibody status (AHR 1.19; 95% CI 0.83, 1.72, P = 0.35). Liver‐related mortality was associated with age >50 [AHR 18.49 vs <40 years (referent group); 95% CI 2.27, 150.41, P < 0.001] and positive HCV antibody status (AHR 7.69; 95% CI 0.99, 59.98, P = 0.052). This study demonstrates a high rate of mortality in this population, particularly those with HIV. HCV‐infected inner city residents >50 years of age were at significant risk of liver‐related mortality. Continued surveillance of this population infected with HCV in the 1970s and 1980s is important.