Abstract
Recognizing the importance of timely guidance regarding the rapidly evolving field of hepatitis C management, the American Association for the Study of Liver Diseases (AASLD) and the ...Infectious Diseases Society of America (IDSA) developed a web-based process for the expeditious formulation and dissemination of evidence-based recommendations. Launched in 2014, the hepatitis C virus (HCV) guidance website undergoes periodic updates as necessitated by availability of new therapeutic agents and/or research data. A major update was released electronically in September 2017, prompted primarily by approval of new direct-acting antiviral agents and expansion of the guidance's scope. This update summarizes the latest release of the HCV guidance and focuses on new or amended recommendations since the previous September 2015 print publication. The recommendations herein were developed by volunteer hepatology and infectious disease experts representing AASLD and IDSA and have been peer reviewed and approved by each society's governing board.
To estimate the joint effects of substance use disorder (SUD) and recent substance use on human immunodeficiency virus (HIV) non-suppression.
Retrospective clinical cohort study with repeated ...observations within individuals.
Baltimore, Maryland, United States.
1881 patients contributed 10 794 observations.
The primary independent variable was the combination of history of SUD and recent substance use. History of SUD was defined as any prior International Classification of Diseases 9/10 code for cocaine or opioid disorder. Recent substance use was defined as the self-report of cocaine or non-prescribed opioid use on the National Institute of Drug Abuse-modified Alcohol, Smoking and Substance Involvement Screening Test or clinician-documented cocaine or opioid use abstracted from the medical record. The outcome was viral non-suppression, defined as HIV RNA >200 copies/mL on the first viral load measurement within 1 year subsequent to each observation of substance use. We adjusted for birth sex, Black race, age, HIV acquisition risk factors, years in care and CD4 cell count. In secondary analyses, we also adjusted for depressive, anxiety and panic symptoms, cannabis use and cannabis use disorder.
On their first observation, 31% of patients had a history of an SUD and 18% had recent substance use. Relative to no history of SUD and no recent substance use, the 1-year fully adjusted risk difference (RD) for viral non-suppression associated with cocaine and opioid use disorder and recent substance use was 7.7% (95% CI = 5.3%-10.0%), the RD was 5.5% (95% CI = 1.2%-9.7%) for history of cocaine use disorder without recent substance use, and the RD was 4.6% (95% CI = 2.7%-6.5%) for recent substance use without a SUD.
Substance use and substance use disorders appear to be highly prevalent among, and independently associated with, viral non-suppression among people with HIV.
Hepatitis C virus (HCV) cure rates have been similar in patients with and without human immunodeficiency virus (HIV) coinfection; however, in the ION‐4 study, black patients treated with ...ledipasvir/sofosbuvir (LDV/SOF) were significantly less likely to achieve cure (90%) compared to nonblack patients (99%). There are limited real‐world data on the effectiveness of oral direct‐acting antivirals (DAAs) in predominantly minority HIV/HCV coinfected populations. We analyzed HCV treatment outcomes among 255 HCV coinfected patients initiating DAAs between February 2014 and March 2016 in an urban clinic in Baltimore, Maryland. To facilitate adherence, patients received standardized HIV nurse/pharmacist support, which included nurse visits and telephone calls. Median age was 43 years, 88% were black, 73% male, 69% had a history of injection drug use, 45% a history of hazardous alcohol use, and 57% a comorbid psychiatric diagnosis. Median CD4 count was 577 (interquartile range, 397‐820) cells/mm3; most (97%) were on antiretroviral therapy, had HIV RNA <20 copies/mL (87%), and were infected with HCV genotype 1 (98%). Over 60% had significant fibrosis (Fibrosis‐4 Index score 1.45‐3.25 44% and >3.25 17%, cirrhosis) and 30% were HCV treatment experienced. The majority of patients received LDV/SOF with or without ribavirin (91%) and were treated for 12 weeks. Overall, the sustained virological response rate was 97% (95% confidence interval CI, 93‐98) and did not vary by race (black, 96% 95% CI, 93‐98; nonblack, 97%, 95% CI, 83‐99), history of injection drug use, alcohol use, or psychiatric diagnosis. Conclusion: HCV treatment was highly effective among HIV‐infected patients who received care within an integrated nurse/pharmacist adherence support program. These results suggest that race and psychosocial comorbidity may not be barriers to HCV elimination. (Hepatology 2017;66:1402–1412).
Background and Aims
Direct‐acting antivirals (DAAs) are highly effective in treating hepatitis C. However, there is concern that cure rates may be lower, and reinfection rates higher, among people ...who inject drugs. We conducted a systematic review of treatment outcomes achieved with DAAs in people who inject drugs (PWID).
Methods
A search strategy was used to identify studies that reported sustained viral response (SVR), treatment discontinuation, adherence or reinfection in recent PWID and/or opioid substitution therapy (OST) recipients. Study quality was assessed using the Newcastle‐Ottawa Scale. Meta‐analysis of proportions was used to estimate pooled SVR and treatment discontinuation rates. The pooled relative risk of achieving SVR and pooled reinfection rate were calculated using generalized mixed effects linear models.
Results
The search identified 8075 references; 26 were eligible for inclusion. The pooled SVR for recent PWID was 88% (95% CI, 83%‐92%) and 91% (95% CI 88%‐95%) for OST recipients. The relative risk of achieving SVR for recent PWID compared to non‐recent PWID was 0.99 (95% CI, 0.94‐1.06). The pooled treatment discontinuation was 2% (95% CI, 1%‐4%) for both recent PWID and OST recipients. Amongst recent PWID, the pooled incidence of reinfection was 1.94 per 100 person years (95% CI, 0.87‐4.32). In OST recipients, the incidence of reinfection was 0.55 per 100 person years (95% CI, 0.17‐1.76).
Conclusions
Treatment outcomes were similar in recent PWID compared to non‐PWID treated with DAAs. People who report recent injecting or OST recipients should not be excluded from hepatitis C treatment.
See Editorial on Page 2238
Background
Increased uptake of hepatitis C virus (HCV) treatment among people who inject drugs (PWID) will be critical to achieve HCV elimination goals. There are limited data on HCV treatment uptake ...among PWID recruited from community‐based settings in the HCV direct‐acting antiviral (DAA) era.
Methods
We analysed data from PWID with HCV newly recruited into the Baltimore, Maryland‐based AIDS Linked to the IntraVenous Experience (ALIVE) cohort between 2015 and 2018. We characterized the HCV care continuum and evaluated factors associated with HCV treatment uptake.
Results
Of the 418 PWID with HCV, the median age was 49 years and most (88%) reported recent injection drug use (IDU). Overall, 23% had ever been evaluated by a provider for HCV treatment, 17% ever initiated DAA treatment and 13% were cured of HCV infection. Treatment uptake approximately doubled between 2015 and 2018 (13% to 26%, P = .01). In multivariable analyses, HIV infection (adjusted Odds Ratio aOR 2.5 95% Confidence Interval (CI) 1.3, 4.8), current employment (aOR 4.1 CI 1.2, 14.4), having a primary care provider (aOR 4.3 CI 1.2, 14.9) and longer duration of IDU (aOR 1.3 CI 1.1, 1.6) were positively associated with HCV treatment. PWID with a lower annual income (≤$5000) were less likely to have initiated HCV treatment (aOR 0.5 CI 0.3, 0.98).
Conclusions
Although HCV treatment uptake among PWID in this community‐based setting in the DAA era remains suboptimal, it is encouraging that treatment uptake has increased in recent years. Innovative strategies are needed to reach all PWID infected with HCV.
Background and aims
People who inject drugs (PWID) are at risk for adverse outcomes across multiple dimensions. While evidence‐based interventions are available, services are often fragmented and ...difficult to access. We measured the effectiveness of an integrated care van (ICV) that offered services for PWID.
Design, setting and participants
This was a cluster‐randomized trial, which took place in Baltimore, MD, USA. Prior to randomization, we used a research van to recruit PWID cohorts from 12 Baltimore neighborhoods (sites), currently served by the city's mobile needle exchange program.
Intervention and comparator
We randomized sites to receive weekly visits from the ICV (n = 6) or to usual services (n = 6) for 14 months. The ICV offered case management; buprenorphine/naloxone; screening for HIV, hepatitis C virus and sexually transmitted infections; HIV pre‐exposure prophylaxis; and wound care.
Measurements
The primary outcome was a composite harm mitigation score that captured access to evidence‐based services, risk behaviors and adverse health events (range = 0−15, with higher numbers indicating worse status). We evaluated effectiveness by comparing changes in the composite score at 7 months versus baseline in the two study arms.
Findings
We enrolled 720 cohort participants across the study sites (60 per site) between June 2018 and August 2019: 38.3% women, 72.6% black and 85.1% urine drug test positive for fentanyl. Over a median of 10.4 months, the ICV provided services to 734 unique clients (who may or may not have been cohort participants) across the six intervention sites, including HIV/hepatitis C virus testing in 577 (78.6%) and buprenorphine/naloxone initiation in 540 (74%). However, only 52 (7.2%) of cohort participants received services on the ICV. The average composite score decreased at 7 months relative to baseline, with no significant difference in the change between ICV and usual services (difference in differences: −0.31; 95% confidence interval: −0.70, 0.08; P = 0.13).
Conclusions
This cluster‐randomized trial in Baltimore, MD, USA, found no evidence that weekly neighborhood visits from a mobile health van providing injection‐drug‐focused services improved access to services and outcomes among people who injected drugs in the neighborhood, relative to usual services. The van successfully served large numbers of clients but unexpectedly low use of the van by cohort participants limited the ability to detect meaningful differences.
We evaluated geographic heterogeneity in hepatitis C virus (HCV) treatment penetration among people who inject drug (PWID) across Baltimore, MD since the advent of direct-acting antivirals (DAAs) ...using space-time clusters of HCV viraemia. Using data from a community-based cohort of PWID, the AIDS Linked to the IntraVenous Experience (ALIVE) study, we identified space-time clusters with higher-than-expected rates of HCV viraemia between 2015 and 2019 using scan statistics. We used Poisson regression to identify covariates associated with HCV viraemia and used the regression-fitted values to detect adjusted space-time clusters of HCV viraemia in Baltimore city. Overall, in the cohort, HCV viraemia fell from 77% in 2015 to 64%, 49%, 39% and 36% from 2016 to 2019. In Baltimore city, the percentage of census tracts where prevalence of HCV viraemia was ≥85% dropped from 57% to 34%, 25%, 22% and 10% from 2015 to 2019. We identified two clusters of higher-than-expected HCV viraemia in the unadjusted analysis that lasted from 2015 to 2017 in East and West Baltimore and one adjusted cluster of HCV viraemia in West Baltimore from 2015 to 2016. Neither differences in age, sex, race, HIV status, nor neighbourhood deprivation were able to explain the significant space-time clusters. However, residing in a cluster with higher-than-expected viraemia was associated with age, sex, educational attainment and higher levels of neighbourhood deprivation. Nearly 4 years after DAAs became available, HCV treatment has penetrated all PWID communities across Baltimore city. While nearly all census tracts experienced improvements, change was more gradual in areas with higher levels of poverty.
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.
Summary
Triazole and imidazole antifungal agents inhibit metabolism of vincristine, leading to excess vinca alkaloid exposure and severe neurotoxicity. Recent reports of debilitating interactions ...between vincristine and itraconazole, as well as posaconazole, voriconazole and ketoconazole underscore the need to improve medical awareness of this adverse combination. We, therefore, undertook a comprehensive analysis of reports of adverse drug interactions (ADIs) with the combination of vincristine and azole antifungal agents, established a new classification, and provided a detailed summary of these toxicities. In patients who had sufficient data for analysis, 47 individuals were identified who had an ADI with the combination of vincristine and antifungal azoles. Median age was 8 years (1.3–68 years) with 33(70%) having a diagnosis of acute lymphoblastic leukaemia. Median time to ADI with vincristine was 9.5 days with itraconazole, 13.5 days posaconazole and 30 days voriconazole. The median number of vincristine doses preceding the ADI was 2 doses with itraconazole, 3 doses posaconazole and 2 doses voriconazole. The most common severe ADIs included gastrointestinal toxicity, peripheral neuropathy, hyponatremia/SIADH, autonomic neuropathy and seizures. Recovery from these ADIs occurred in 80.6% of patients. We recommend using alternative antifungal agents if possible in patients receiving vincristine to avoid this serious and potentially life‐threatening drug interaction.
We investigated the prevalence and impact of heavy alcohol use on the hepatitis C virus (HCV) care continuum amongst HIV/HCV co‐infected persons who use drugs. In the CHAMPS study, 144 HIV/HCV ...co‐infected persons were randomized to contingent cash incentives, peer mentors and usual care to evaluate the impact on HCV care. Alcohol use was ascertained using the 10‐item AUDIT (hazardous: male ≥8, female ≥4) and phosphatidylethanol (PEth) (heavy: ≥50 ng/mL), an alcohol biomarker. Log binomial regression was used to evaluate the association between heavy alcohol use and failure to initiate treatment and to achieve sustained virologic response (SVR). Of the 135 participants with PEth data, median age was 55 years, 59% were male, 92% were Black, 91% reported a history of drug use, and 97% were on antiretroviral therapy. Hazardous drinking was reported on AUDIT by 28% of participants, and 35% had heavy alcohol use by PEth. Of the 47 individuals with a PEth ≥50 ng/mL, 23 (49%) reported no or minimal alcohol use by AUDIT. HCV treatment was initiated in 103 of 135 participants, and SVR was achieved in 92%. PEth ≥50 ng/mL (Relative Risk RR 0.72, 95% CI 0.35‐1.48) was not significantly associated with failure to initiate HCV treatment or failure to achieve SVR (RR 0.85, 95% CI 0.46‐1.57).In conclusion, alcohol use was common and frequently not detected by self‐report. However, heavy alcohol use, even when measured objectively, was not associated with failure to initiate HCV treatment or to achieve cure.
PDF
