Publications by authors named "Mark Sulkowski"

269 Publications

T-cell Activation Is Correlated With Monocyte Activation in HCV/HIV Coinfection and Declines During HCV Direct-Acting Antiviral Therapy.

Open Forum Infect Dis 2021 Apr 18;8(4):ofab079. Epub 2021 Feb 18.

Department of Pathology, VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.

Background: Immune activation markers associate with morbidity and mortality in HIV and hepatitis C virus (HCV) infection. We investigated how T-cell and monocyte activation are related over the course of HCV direct-acting antiviral (DAA) therapy during HCV/HIV coinfection.

Methods: Peripheral blood mononuclear cells from AIDS Clinical Trials Group (ACTG) A5329 participants and a single-site separate cohort treated with DAAs were analyzed for central memory (CM)/effector memory (EM) T-cell subsets, monocyte subsets, and cell activation (CD38 and HLA-DR expression) before, during, and after therapy.

Results: Before therapy, classical and inflammatory monocyte subset HLA-DR expression positively correlated with absolute counts and frequencies of CD38HLA-DR-expressing CD4 and CD8 T cells and corresponding CM and EM subsets. After therapy initiation, CD38HLA-DR co-expression on CD4 and CD8 memory T cells decreased by 12 weeks and 36 weeks, and plasma sCD14 positively correlated with CD38HLA-DR CD4 and CD4CM T-cell frequencies. Monocyte subset activation remained similar over time.

Conclusions: During HCV/HIV coinfection, memory T-cell activation is associated with monocyte subset activation, consistent with related underlying mechanisms. Following therapy initiation, memory T-cell, but not monocyte, activation decreased. Residual CD4 T-cell activation after therapy completion is associated with sCD14, potentially linking the remaining CD4 T-cell activation to residual factors driving activation in antiretroviral therapy-controlled HIV.
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http://dx.doi.org/10.1093/ofid/ofab079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043262PMC
April 2021

Factors associated with phosphatidylethanol (PEth) sensitivity for detecting unhealthy alcohol use: An individual patient data meta-analysis.

Alcohol Clin Exp Res 2021 Apr 10. Epub 2021 Apr 10.

West Haven VA Healthcare System, United States Department of Veterans Affairs, West Haven, CT, USA.

Background: Objective measurement of alcohol consumption is important for clinical care and research. Adjusting for self-reported alcohol use, we conducted an individual participant data (IPD) meta-analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self-reporting unhealthy alcohol consumption.

Methods: We identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1-step IPD meta-analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index-BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger-prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self-reported alcohol use using the AUDIT-C score.

Results: One third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT-C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables.

Conclusions: Among people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.
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http://dx.doi.org/10.1111/acer.14611DOI Listing
April 2021

A Prospective Study Evaluating Changes in Histology, Clinical and Virologic Outcomes in HBV-HIV Co-infected Adults in North America.

Hepatology 2021 Mar 20. Epub 2021 Mar 20.

National Cancer Institute, Bethesda.

Introduction: Histological and clinical outcomes in HBV-HIV coinfection in the era of combination antiretroviral therapy (cART) are poorly-defined.

Methods: Adult HBV-HIV co-infected patients from 8 North American sites were enrolled in this NIH-funded prospective observational study (n=139). Demographic, clinical, serological and virological data were collected at entry and every 24 weeks for ≤192 weeks. Paired liver biopsies were obtained at study entry and at ≥3 years of follow-up. Biopsies were assessed by a central pathology committee using Modified Ishak scoring system. Clinical outcome rate and changes in histology are reported.

Results: Among participants with follow-up data (n=114), median age was 49 years, 91% were male, 51% were non-Hispanic Black and 13% had at-risk alcohol use, with a median infection of 20 years. At entry, 95% were on anti-HBV cART. Median CD4 count was 562 cells/mm and 93% had HIV <400 copies/mL. HBeAg was positive in 61% and HBV DNA was below the limit of quantification (<20 IU/mL) in 61%; <1000 IU/mL in 80%. Clinical events were uncommon across follow-up: 1 hepatic decompensation, 2 hepatocellular carcinoma, no liver transplants and 1 HBV-related deaths, with a composite endpoint rate of 0.61/100 person-years. Incident cirrhosis (n=1), ALT flare (n=2), and HBeAg loss (n=13) rates were 0.40, 0.65 and 6.86/100 person-years, respectively. No participants had HBsAg loss. Paired biopsy (n=62; median 3.6 years apart) revealed minimal improvement in Histologic Activity Index (median [IQR]: 3 [2-4] to 3 [1-3]; P=.02) and no significant change in fibrosis score (1 [1-2] to 1 [0-3]; P=.58).

Conclusions: In a North American cohort of adults with HBV-HIV on cART with virological suppression, clinical outcomes and worsening histological disease were uncommon.
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http://dx.doi.org/10.1002/hep.31823DOI Listing
March 2021

Performance of Serum-Based Scores for Identification of Mild Hepatic Steatosis in HBV Mono-infected and HBV-HIV Co-infected Adults.

Dig Dis Sci 2021 Feb 8. Epub 2021 Feb 8.

National Institutes of Health, Bethesda, USA.

Background: There are limited data on noninvasive methods to identify hepatic steatosis in coexisting hepatitis B virus (HBV) infection.

Aims: To evaluate the diagnostic performance of noninvasive serum-based scores to detect steatosis using two distinct chronic HBV cohorts with liver histology evaluation.

Methods: Chronic HBV cohorts with untreated HBV mono-infection (N = 302) and with treated HBV-HIV (N = 92) were included. Liver histology was scored centrally. Four serum-based scores were calculated: hepatic steatosis index (HSI), nonalcoholic fatty liver disease Liver Fat Score (NAFLD-LFS), visceral adiposity index (VAI), and triglyceride glucose (TyG) index. Optimal cutoffs (highest sensitivity + specificity) to detect ≥ 5% HS, stratified by cohort, were evaluated.

Results: HBV-HIV (vs. HBV mono-infected) patients were older (median 50 vs. 43 years), and a higher proportion were male (92% vs. 60%), were black (51% vs. 8%), had the metabolic syndrome (41% vs. 25%), and suppressed HBV DNA (< 1000 IU/mL; 82% vs. 9%). Applying optimal cutoffs, the area under the receiver operator curve for detecting ≥ 5% steatosis in HBV-only and HBV-HIV, respectively, was 0.69 and 0.61 for HSI, 0.70 and 0.76 for NAFLD-LFS, 0.68 and 0.64 for TyG, and 0.68 and 0.69 for VAI. The accuracy of optimal cutoffs ranged from 61% (NAFLD-LFS) to 67% (TyG) among HBV-only and 56% (HSI) to 76% (NAFLD-LFS) among HBV-HIV. Negative predictive values were higher than positive predictive values for all scores in both groups.

Conclusion: The relative utility of scores to identify steatosis in chronic HBV differs by co-infection/anti-HBV medication status. However, even with population-specific cutoffs, several common serum-based scores have only moderate utility. ClinicalTrials.gov NCT01924455.
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http://dx.doi.org/10.1007/s10620-021-06860-3DOI Listing
February 2021

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

Am J Transplant 2021 May 23;21(5):1780-1788. Epub 2020 Dec 23.

Department of Surgery, University of California, San Francisco, California, USA.

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4 years and post-LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.
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http://dx.doi.org/10.1111/ajt.16427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096639PMC
May 2021

Hepatitis C Virus Treatment: Simplifying the Simple and Optimizing the Difficult.

J Infect Dis 2020 11;222(Suppl 9):S745-S757

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

The availability of safe, efficacious, oral direct-acting antivirals (DAAs) have ushered in a new era of hepatitis C treatment with potential to eliminate hepatitis C as a public health threat. To achieve population-level effectiveness of these oral DAAs, hepatitis C treatment by a wide range of providers in different settings will be essential to increase the number of persons treated. We provide a clinical review of hepatitis C treatment with a focus on practical tools for management of hepatitis C in majority of currently infected individuals who can be easily cured and optimization of treatment for those in whom treatment may not be as simple.
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http://dx.doi.org/10.1093/infdis/jiaa534DOI Listing
November 2020

Factors associated with phylogenetic clustering of hepatitis C among people who inject drugs in Baltimore.

BMC Infect Dis 2020 Nov 10;20(1):815. Epub 2020 Nov 10.

Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

Background: The availability of effective, oral direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has put elimination of HCV as a public health challenge within reach. However, little is known about the characteristics of transmission networks of people who inject drugs (PWID).

Methods: Sequencing of a segment of the HCV genome was performed on samples collected from a community-based cohort of PWID between August 2005 and December 2016. Phylogenetic trees were inferred, and clusters were identified (70% bootstrap threshold; 0.04 maximum genetic distance threshold). We describe sex, race, age difference, and HIV infection status of potential transmission partners. Logistic regression was used to assess factors associated with being in an HCV cluster.

Results: Of 508 HCV genotype 1 viremic PWID, 8% (n = 41) were grouped into 20 clusters, consisting of 19 pairs and 1 triad. In adjusted analyses, female sex (odds ratio [OR] 2.3 [95% confidence interval (CI) 1.2-4.5]) and HIV infection (OR 5.7 [CI 2.7-11.9]) remained independently associated with being in an HCV infection cluster.

Conclusions: Molecular epidemiological analysis reveals that, in this cohort of PWID in Baltimore, HIV infection and female sex were associated with HCV clustering. Combination HCV prevention interventions targeting HIV infected PWID and addressing HCV infection prevention needs of women have potential to advance HCV elimination efforts.
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http://dx.doi.org/10.1186/s12879-020-05546-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652590PMC
November 2020

Perceptions of network based recruitment for hepatitis C testing and treatment among persons who inject drugs: a qualitative exploration.

Int J Drug Policy 2021 Feb 4;88:103019. Epub 2020 Nov 4.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Background: Social network interventions that take advantage of existing individual and group relationships may help overcome the significant patient, provider, and system level barriers that contribute to low hepatitis C Virus (HCV) treatment uptake among people who inject drugs (PWID).

Methods: We conducted semi-structured interviews with 20 HCV antibody positive PWID (15 male, 5 female) in Baltimore, Maryland, USA. We utilized thematic analysis and employed both inductive and deductive coding techniques to assess perceptions of barriers and facilitators of social network interventions for HCV testing, linkage to care, and treatment among PWID.

Results: PWID perceived a high prevalence of HCV within their social networks, especially within injection drug use networks. Overwhelmingly, participants reported a willingness to discuss HCV and provide informational, instrumental, and emotional support to their network members. Support included sharing knowledge, such as where and how to access HCV care, as well as sharing lived experiences about HCV treatment that could help peers build trust within networks. Participants who were already linked into HCV care had an increased understanding of using social network interventions to provide peer navigation, by accompanying network members to HCV related appointments. Across interviews, drug use related stigma and feeling undeserving of HCV treatment due to previous negative experiences accessing the health care system emerged as a major barrier to linkage to HCV treatment and cure. Undeservingness was often internalized and projected onto network members. To overcome this, participants supported access to low-barrier HCV treatment in alternative locations such as community-based or mobile clinics and drug treatment centers.

Conclusion: Social network based interventions have potential to increase HCV treatment uptake among PWID. To be successful, these interventions will need to train peers to share accurate information and personal experiences with HCV testing and treatment and enhance their ability to provide support to network members who face significant stigma related to both HCV and drug use.
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http://dx.doi.org/10.1016/j.drugpo.2020.103019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005423PMC
February 2021

Estimating the Year Each State in the United States Will Achieve the World Health Organization's Elimination Targets for Hepatitis C.

Adv Ther 2021 01 3;38(1):423-440. Epub 2020 Nov 3.

Rush University Medical Center, Chicago, IL, USA.

Introduction: Although hepatitis C virus (HCV) infection remains a major clinical, economic, and societal burden, the development of curative antiviral therapy may accelerate the path toward elimination. This analysis assessed the progress of United States (US) states towards achieving the World Health Organization's (WHO) 2030 HCV elimination targets for incidence, mortality, diagnosis, and treatment.

Methods: A previously published Markov model was used to simulate HCV progression over time to estimate the path to HCV elimination in each state based on prevalence, annual treatment, and diagnosis inputs from two large US laboratory datasets from January 2013 to December 2017. State-specific fibrosis stage restrictions on treatment in 2017 were included. The model estimated the year individual states would meet the WHO targets for diagnosing 90% of the HCV-infected population, treating 80% of the eligible population, reducing new HCV infections by 80%, and reducing HCV-related deaths by 65%. The minimum number of annual treatments needed between 2020 and 2030 to achieve the WHO treatment target was also calculated.

Results: Overall, the USA is projected to achieve HCV elimination by 2037, with individual targets related to mortality, diagnosis, treatment, and incidence being achieved by 2020, 2027, 2033, and 2037, respectively. Three states (Connecticut, South Carolina, and Washington) are on track to meet all four elimination targets by 2030, and 18 states are not expected to meet these targets before 2040. The estimated annual number of treatments required during 2020-2030 nationally to reach the WHO treatment target is 173,514.

Conclusion: With the exception of three states, the USA is not on target to meet the WHO 2030 elimination targets and 35% are off track by 10 years or more. Strategies must be implemented to reduce overall prevalence by preventing new infections, increasing rates of screening, improving linkage to care, and implementing unfettered access to curative therapy.
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http://dx.doi.org/10.1007/s12325-020-01535-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609357PMC
January 2021

Expert Panel Review on Non-Alcoholic Fatty Liver Disease in Persons With HIV.

Clin Gastroenterol Hepatol 2020 Oct 16. Epub 2020 Oct 16.

Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Nonalcoholic fatty liver disease (NAFLD) affects 25% of adults in the general population and is a disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) to end-stage liver disease. NAFLD is an independent risk factor for cardiovascular disease, diabetes mellitus, and all-cause mortality, and NASH cirrhosis is a frequent indication for liver transplantation. In persons with human immunodeficiency virus (PWH), chronic liver disease is the second leading cause of non-human immunodeficiency virus-related mortality. Between 20% and 63% of PWH have NASH, and 14% to 63% have NASH with fibrosis. However, little is known about the optimal diagnostic strategies, risk factors for, and treatment of NAFLD in PWH. Here, we review current data on and identify knowledge gaps in the epidemiology, pathophysiology, diagnosis, and management of NAFLD in PWH and highlight priorities for research.
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http://dx.doi.org/10.1016/j.cgh.2020.10.018DOI Listing
October 2020

Single hepatocytes show persistence and transcriptional inactivity of hepatitis B.

JCI Insight 2020 10 2;5(19). Epub 2020 Oct 2.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

There is no cure for the more than 270 million people chronically infected with HBV. Nucleos(t)ide analogs (NUCs), the mainstay of anti-HBV treatment, block HBV reverse transcription. NUCs do not eliminate the intranuclear covalently closed circular DNA (cccDNA), from which viral RNAs, including pregenomic RNA (pgRNA), are transcribed. A key gap in designing a cure is understanding how NUCs affect HBV replication and transcription because serum markers yield an incomplete view of intrahepatic HBV. We applied single-cell laser capture microdissection and droplet digital PCR to paired liver biopsies collected from 5 HBV/HIV-coinfected persons who took NUCs over 2-4 years. From biopsy 1 to 2, proportions of HBV-infected hepatocytes declined with adherence to NUC treatment (P < 0.05); we extrapolated that eradication of HBV will take over 10 decades with NUCs in these participants. In individual hepatocytes, pgRNA levels diminished 28- to 73-fold during NUC treatment, corresponding with decreased tissue HBV core antigen staining (P < 0.01). In 4 out of 5 participants, hepatocytes with cccDNA but undetectable pgRNA (transcriptionally inactive) were present, and these were enriched in 3 participants during NUC treatment. Further work to unravel mechanisms of cccDNA transcriptional inactivation may lead to therapies that can achieve this in all hepatocytes, resulting in a functional cure.
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http://dx.doi.org/10.1172/jci.insight.140584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566712PMC
October 2020

The Economic Value of Improved Productivity from Treatment of Chronic Hepatitis C Virus Infection: A Retrospective Analysis of Earnings, Work Loss, and Health Insurance Data.

Adv Ther 2020 11 14;37(11):4709-4719. Epub 2020 Sep 14.

AbbVie, Inc., Mettawa, IL, USA.

Introduction: Patients with chronic hepatitis C virus infection (HCV) may incur significant indirect costs due to health-related work loss. However, the impact of curative HCV therapy on work productivity is not well characterized. We estimated the economic value of improved productivity following HCV treatment.

Methods: Adults diagnosed with HCV infection (Optum Healthcare Solutions data; Q1 1999 to Q1 2017) were stratified into two cohorts: (1) treated cohort, patients who received HCV therapy and (2) untreated cohort, therapy-naïve patients. For the treated cohort, the index date was set at the end of the post-treatment monitoring period, assumed to be 6 months after the end of treatment for patients with cirrhosis or for those treated with interferon-based therapy, and 3 months after the end of treatment for patients without cirrhosis who received interferon-free therapy. For the untreated cohort, an index date was randomly selected post-HCV diagnosis. Time from the index date to the first work-loss event was assessed using time to event analyses. An economic modeling approach was used to monetize the improved productivity from reduced risk of work-loss event in the 4 years post-index.

Results: Patients in the treated cohort had a lower risk of experiencing a work-loss event compared to untreated patients [unadjusted and adjusted hazard ratios and 95% CI 0.72 (0.61-0.86), and 0.68 (0.55-0.85), respectively; p < 0.001 for both]. The mean cumulative added productivity value associated with HCV treatment was US$4511 (CI $2778-$6278) at 1 year post-index and $21,429 (CI $12,733-$30,199) at 4 years post-index.

Conclusion: HCV treatment reduces the risk of work loss resulting in productivity gains for employers and employees. The monetary value associated with these productivity gains is substantial, and, after about 4 years, it is comparable to the wholesale acquisition cost of some direct-acting antiviral regimens in the United States. Employers may derive economic benefits from adopting HCV elimination strategies.
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http://dx.doi.org/10.1007/s12325-020-01492-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547965PMC
November 2020

Four-Week Direct-Acting Antiviral Prophylaxis for Kidney Transplantation From Hepatitis C-Viremic Donors to Hepatitis C-Negative Recipients: An Open-Label Nonrandomized Study.

Ann Intern Med 2021 01 8;174(1):137-138. Epub 2020 Sep 8.

Johns Hopkins University School of Medicine, Baltimore, Maryland (C.M.D., B.B., S.Y., D.M.B., M.A.C., N.B., F.F.N., M.S., D.L.S., N.M.D.).

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http://dx.doi.org/10.7326/M20-1468DOI Listing
January 2021

Déjà vu all over again: retreatment of HCV DAA failures- same satisfactory results, same unanswered questions.

Clin Infect Dis 2020 Sep 5. Epub 2020 Sep 5.

Denver Health Medical Center, Denver, Colorado, USA.

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http://dx.doi.org/10.1093/cid/ciaa1329DOI Listing
September 2020

Fatty Liver Disease in a Prospective North American Cohort of Adults with HIV and Hepatitis B Coinfection.

Clin Infect Dis 2020 Sep 1. Epub 2020 Sep 1.

Virginia Commonwealth University, Richmond.

Background: Hepatitis B (HBV) and fatty liver disease (FLD) are common etiologies of liver disease in HIV. Correlates of FLD and its relationship with alanine aminotransferase (ALT) overtime were examined in HIV-HBV coinfection.

Methods: From 04/28/14-11/07/18, 114 HIV-HBV adults underwent a liver biopsy and were followed for a median of 3 years (ancillary study of Hepatitis B Research Network). Steatohepatitis was based on presence of steatosis, ballooning and perisinusoidal fibrosis. FLD was defined as ≥5% steatosis and/or steatohepatitis.

Results: Median age was 49 years, 93% were male, 51% black, 93% had HIV RNA<400 copies/mL and 83% HBV DNA<1000 IU/mL. Thirty percent had FLD (20% steatosis, 10% steatohepatitis). Those with FLD had higher median triglyceride (171 versus 100 mg/dL, P<.01) and sdLDL (44 versus 29 mg/dL, P<.01) and lower HDL-2C (9 versus 12 mg/dL, P=.001). After adjusting for age, sex and alcohol use, white and other vs. black race (odds ratio [OR]=8.49 and OR=16.54, respectively, P=.0004), ALT (OR=3.13 per doubling, P=.003), hypertension (OR=10.93, P=.002), hyperlipidemia (OR=4.36, P=.04) and diabetes family history (OR=5.38, P=.02) were independently associated with having FLD. Steatohepatitis or steatosis alone (versus none) were associated with higher ALT overtime (1.93 and 1.34 times higher, respectively; P<.001), with adjustment for age, sex, and HBV DNA.

Conclusions: About 30% with HIV-HBV coinfection had FLD including 10% with steatohepatitis. FLD was associated with non-black race, metabolic risks, an increased atherogenic lipid profile, and elevated ALT overtime. Thus, identification of FLD and management of adverse metabolic profiles is critically important in HIV-HBV coinfection.
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http://dx.doi.org/10.1093/cid/ciaa1303DOI Listing
September 2020

Hepatitis C treatment uptake among people who inject drugs in the oral direct-acting antiviral era.

Liver Int 2020 10;40(10):2407-2416

Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

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.
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http://dx.doi.org/10.1111/liv.14634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706292PMC
October 2020

Sharing the cure: Building primary care and public health infrastructure to improve the hepatitis C care continuum in Maryland.

J Viral Hepat 2020 12 5;27(12):1388-1395. Epub 2020 Aug 5.

Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

In 2014, trained healthcare provider capacity was insufficient to deliver care to an estimated 70 000 persons in Maryland with chronic hepatitis C virus (HCV) infection. The goal of Maryland Community Based Programs to Test and Cure Hepatitis C, a public health implementation project, was to improve HCV treatment access by expanding the workforce. Sharing the Cure (STC) was a package of services deployed 10/1/14-9/30/18 that included enhanced information technology and public health infrastructure, primary care provider training and practice transformation. Nine primary care sites enrolled. HCV clinical outcomes were documented among individuals who presented for care at sites and met criteria for HCV testing including risk factor or birth cohort (born between 1945 and 1965) based testing. Fifty-three providers completed the STC training. STC providers identified 3237 HCV antibody-positive patients of which 2624 (81%) were RNA+. Of those HCV RNA+, 1739 (66%) were staged, 932 (36%) were prescribed treatment, 838 (32%) started treatment, 721 (27%) completed treatment and 543 (21%) achieved cure. Among 1739 patients staged, 693 (40%) patients had a liver fibrosis assessment score < F2, rendering them ineligible for treatment under Maryland Medicaid guidelines. HCV RNA testing among HCV antibody-positive people increased from 40% (baseline) to 95% among STC providers. Of 554 patients with virologic data reported, 543 (98%) achieved cure. Primary care practices can effectively serve as HCV treatment centers to expand treatment access. However, criteria by insurance providers in Maryland were a major barrier to treatment.
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http://dx.doi.org/10.1111/jvh.13360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721959PMC
December 2020

REPLACING INSULIN WITH ANTI-VIRALS: A CLINICAL VIGNETTE ON DIABETES AND HCV TREATMENT.

AACE Clin Case Rep 2020 Mar-Apr;6(2):e59-e61. Epub 2020 Jan 22.

Objective: There is growing evidence to support a connection between type 2 diabetes mellitus (T2DM) and chronic hepatitis C virus (HCV). Patients with hepatitis C have a substantially higher risk for developing type 2 diabetes and recently there have been several proposed mechanisms. Several retrospective studies have demonstrated a small but significant improvement in glycemic control after treatment of underlying hepatitis C virus. We describe a case that demonstrates the greatest recorded improvement in glycemic control after treatment of HCV in the setting of self-discontinuation of insulin therapy without behavioral modification.

Methods: A 38-year-old obese female with uncontrolled T2DM (hemoglobin A1c [HbA1c] of 11.6% [103 mmol/mol]) was temporarily lost to follow-up and reported nonadherence to insulin therapy, metformin therapy, diet, or exercise. During this time, she was successfully treated for hepatitis C and became euglycemic without other interventions.

Results: The patient's HbA1c decreased from 11.6 to 5.7% (103 to 39 mmol/mol) in the presence of weight gain and in the absence of any intervention other than hepatitis C treatment.

Conclusion: Hepatitis C treatment may offer significant potential for improving insulin sensitivity and decreasing long-term complications of type 2 diabetes in certain patients. Universal treatment of HCV could offer benefits in both hepatic and extrahepatic clinical outcomes.
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http://dx.doi.org/10.4158/ACCR-2019-0369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282150PMC
January 2020

Ethical and Practical Issues Associated With the Possibility of Using Controlled Human Infection Trials in Developing a Hepatitis C Virus Vaccine.

Clin Infect Dis 2020 12;71(11):2986-2990

School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Despite the existence of established treatments for hepatitis C virus (HCV), more effective means of preventing infection, such as a vaccine, are arguably needed to help reduce substantial global morbidity and mortality. Given the expected challenges of developing such a vaccine among those at heightened risk of infection, controlled human infection studies seem to be a promising potential approach to HCV vaccine development, but they raise substantial ethical and practical concerns. In this article, we describe some of the challenges related to the possibility of using controlled human infection studies to accelerate HCV vaccine development. The related ethical and practical concerns require further deliberation before such studies are planned and implemented.
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http://dx.doi.org/10.1093/cid/ciaa640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778335PMC
December 2020

Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine.

Proc Natl Acad Sci U S A 2020 06 18;117(22):11987-11994. Epub 2020 May 18.

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;

Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis worldwide and kills more Americans than 59 other infections, including HIV and tuberculosis, combined. While direct-acting antiviral (DAA) treatments are effective, limited uptake of therapy, particularly in high-risk groups, remains a substantial barrier to eliminating HCV. We developed a long-acting DAA system (LA-DAAS) capable of prolonged dosing and explored its cost-effectiveness. We designed a retrievable coil-shaped LA-DAAS compatible with nasogastric tube administration and the capacity to encapsulate and release gram levels of drugs while resident in the stomach. We formulated DAAs in drug-polymer pills and studied the release kinetics for 1 mo in vitro and in vivo in a swine model. The LA-DAAS was equipped with ethanol and temperature sensors linked via Bluetooth to a phone application to provide patient engagement. We then performed a cost-effectiveness analysis comparing LA-DAAS to DAA alone in various patient groups, including people who inject drugs. Tunable release kinetics of DAAs was enabled for 1 mo with drug-polymer pills in vitro, and the LA-DAAS safely and successfully provided at least month-long release of sofosbuvir in vivo. Temperature and alcohol sensors could interface with external sources for at least 1 mo. The LA-DAAS was cost-effective compared to DAA therapy alone in all groups considered (base case incremental cost-effectiveness ratio $39,800). We believe that the LA-DAA system can provide a cost-effective and patient-centric method for HCV treatment, including in high-risk populations who are currently undertreated.
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http://dx.doi.org/10.1073/pnas.2004746117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275718PMC
June 2020

Hepatitis C Virus (HCV) Direct-Acting Antiviral Therapy in Persons With Human Immunodeficiency Virus-HCV Genotype 1 Coinfection Resulting in High Rate of Sustained Virologic Response and Variable in Normalization of Soluble Markers of Immune Activation.

J Infect Dis 2020 09;222(8):1334-1344

University of Colorado School of Medicine, Denver, Colorado, USA.

Background: Hepatitis C virus (HCV) direct-acting antivirals are highly effective. Less is known about changes in markers of immune activation in persons with human immunodeficiency virus (HIV) in whom a sustained virologic response (SVR) is achieved.

Methods: We conducted a nonrandomized clinical trial of 12 or 24 weeks of paritaprevir-ritonavir-ombitasvir plus dasabuvir (PrOD) with or without ribavirin in persons with HCV-1/HIV coinfection suppressed with antiretroviral therapy. Plasma HCV, soluble CD14 (sCD14), interferon-inducible protein 10, soluble CD163 (sCD163), interleukin 6 (IL-6), interleukin 18, monocyte chemoattractant protein (MCP-1), autotaxin (ATX), and Mac2-binding protein (Mac2BP) were measured over 48 weeks.

Results: Participants were treated with PrOD for 12 (n = 9) or 24 (n = 36) weeks; the SVR rate at 12 weeks was 93%. At baseline, cirrhosis was associated with higher ATX and MCP-1, female sex with higher ATX and IL-6, older age with higher Mac2BP, higher body mass index with higher ATX, and HIV-1 protease inhibitor use with higher sCD14 levels. In those with SVR, interferon-inducible protein 10, ATX, and Mac2BP levels declined by week 2, interleukin 18 levels declined by the end of treatment, sCD14 levels did not change, and sCD163, MCP-1, and IL-6 levels changed at a single time point.

Conclusions: During HIV/HCV coinfection, plasma immune activation marker heterogeneity is in part attributable to age, sex, cirrhosis, body mass index, and/or type of antiretroviral therapy. HCV treatment with paritaprevir-ritonavir-ombitasvir plus dasabuvir is highly effective and is associated with variable rate and magnitude of decline in markers of immune activation.

Clinical Trials Registration: NCT02194998.
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http://dx.doi.org/10.1093/infdis/jiaa254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749191PMC
September 2020

Impact of a digital medicine programme on hepatitis C treatment adherence and efficacy in adults at high risk for non-adherence.

Aliment Pharmacol Ther 2020 06 30;51(12):1384-1396. Epub 2020 Apr 30.

Denver, CO.

Background: Direct-acting anti-virals (DAA) are highly effective for hepatitis C virus (HCV) treatment, but perceived risks of medication non-adherence may restrict access to care. Digital medicine programme (DMP) has improved adherence and outcomes for some conditions.

Aims: To conduct a prospective, single-arm, open-label study across the United States to assess the impact of DMP on adherence and efficacy in adults with chronic HCV infection at high risk for non-adherence.

Methods: Eligible participants were placed on the DMP to evaluate real-time adherence; primary outcome was sustained virological response (SVR) at ≥10 weeks post-treatment.

Results: Between August 2017 and April 2019, 288 participants (Medicaid, 64.9%; psychiatric disorders, 61.1%; homeless, 9.4%) received DAAs for 8-12 weeks (sofosbuvir/velpatasvir or ledipasvir, 45%; glecaprevir/pibrentasvir, 55%). SVR was achieved in 99.1% of 218 participants who had HCV RNA assessed at ≥10 weeks post-treatment; of the 70 participants who did not have SVR assessed, 17 had SVR4 with HCV RNA assessed at a median (IQR; interquartile range) 5.6 weeks (4.1, 7.9) post-treatment; one completed treatment but did not have HCV RNA assessed, and 52 discontinued treatment early without assessment. Overall, the primary analysed participants (n = 218) actively used the DMP for median (range) 92.9% (12.5%, 100%) of their prescribed treatment time, and overall pill-taking adherence was 95.0% (57.1%, 100%). Participants reported the programme was useful and easy to use through satisfaction surveys.

Conclusions: HCV treatment with DMP was accepted by patients and clinicians and may support HCV treatment outcomes among patients at high risk for treatment non-adherence (Clinical trials.gov NCT03164902).
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http://dx.doi.org/10.1111/apt.15707DOI Listing
June 2020

Public Masking: An Urgent Need to Revise Global Policies to Protect against COVID-19.

Am J Trop Med Hyg 2020 06;102(6):1160-1161

Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.4269/ajtmh.20-0305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253086PMC
June 2020

Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy.

J Infect Dis 2020 07;222(4):601-610

Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.

Background: Direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) have revolutionized outcomes in human immunodeficiency virus (HIV) coinfection.

Methods: We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons coinfected with suppressed HIV: 5 of 6 treatment-naive enrollees completed A5335S.

Results: Mean baseline plasma HCV ribonucleic acid (RNA) = 6.7 log10 IU/mL and changed by -4.1 log10 IU/mL by Day 7. In liver, laser capture microdissection was used to quantify HCV. At liver biopsy 1, mean %HCV-infected cells = 25.2% (95% confidence interval [CI], 7.4%-42.9%), correlating with plasma HCV RNA (Spearman rank correlation r = 0.9); at biopsy 2 (Day 7 in 4 of 5 participants), mean %HCV-infected cells = 1.0% (95% CI, 0.2%-1.7%) (P < .05 for change), and DAAs were detectable in liver. Plasma C-X-C motif chemokine 10 (CXCL10) concentrations changed by mean = -160 pg/mL per day at 24 hours, but no further after Day 4.

Conclusions: We conclude that HCV infection is rapidly cleared from liver with DAA leaving <2% HCV-infected hepatocytes at Day 7. We extrapolate that HCV eradication could occur in these participants by 63 days, although immune activation might persist. Single-cell longitudinal estimates of HCV clearance from liver have never been reported previously and could be applied to estimating the minimum treatment duration required for HCV infection.
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http://dx.doi.org/10.1093/infdis/jiaa126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377286PMC
July 2020

Individual and network factors associated with HCV treatment uptake among people who inject drugs.

Int J Drug Policy 2020 04 2;78:102714. Epub 2020 Mar 2.

Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Background: Hepatitis C virus (HCV) treatment uptake among people who inject drugs (PWID), a population with disproportionately high rates of HCV, remains low. Peers have been shown to positively impact a broad range of health outcomes for PWID. There is, however, limited data on the impact of PWID social network members on HCV treatment.

Methods: HCV-infected PWID enrolled in an ongoing community-based cohort were recruited as "indexes" to complete an egocentric social network survey. The survey elicited from the index PWID a list of their network members and the index's perception of network member characteristics. Logistic regression analyses were conducted to compare individual and network factors associated with HCV treatment in the index PWID.

Results: Among 540 HCV-infected PWID, the mean age was 55.7 years and the majority were black (87.2%) and male (69.8%). PWID reported a mean of 4.4 (standard deviation [SD] 3.2) network members, most of whom were relatives (mean 2.2 [SD 1.5]). In multivariable analysis, increasing index age and HIV infection were positively associated with HCV treatment, while drug use and homelessness in the preceding 6 months were negatively associated with HCV treatment. From a network perspective, having at least one network member who regularly talked with the index about seeing their doctor for HIV care was associated with HCV treatment (Adjusted Odds Ratio [AOR] 2.7; 95% Confidence Interval (CI) [1.3, 5.6]). Conversely, PWID who had at least one network member who helped them understand their HCV care were less likely to have been HCV treated (AOR 0.2; CI [0.1, 0.6).

Conclusion: HCV treatment uptake in this group of PWID appeared to be positively influenced by discussions with network members living with HIV who were in care and negatively influenced by HCV information sharing within PWID networks. These findings underscore the influence of peers on health seeking behaviors of their network members and emphasizes the importance of well-informed peers.
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http://dx.doi.org/10.1016/j.drugpo.2020.102714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367433PMC
April 2020

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

J Viral Hepat 2020 07 2;27(7):663-670. Epub 2020 Mar 2.

Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

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.
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http://dx.doi.org/10.1111/jvh.13274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299737PMC
July 2020

Addressing the global burden of hepatitis B virus while developing long-acting injectables for the prevention and treatment of HIV.

Lancet HIV 2020 06 20;7(6):e443-e448. Epub 2019 Dec 20.

School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

The first long-acting formulations of HIV drugs are undergoing regulatory review for use in maintenance of viral suppression in people with HIV. Although these novel drug formulations could contribute greatly to HIV treatment and prevention efforts, their lack of activity against hepatitis B virus (HBV) could limit their global impact, particularly in populations with high burdens of both HIV and HBV. An urgent need for greater investment in research and development of long-acting drugs with dual activity against HIV and HBV exists. Access to long-acting HIV drug formulations with dual activity against HBV would be transformative and have a great impact on efforts to prevent, treat, and eradicate both of these important global epidemics.
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http://dx.doi.org/10.1016/S2352-3018(19)30342-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376366PMC
June 2020

Management of the Patient With HIV/Hepatitis C Drug Interactions: A Guide for Nurses and Nurse Practitioners.

J Assoc Nurses AIDS Care 2020 Mar-Apr;31(2):241-248

Approximately one third of patients coinfected with HIV and hepatitis C virus (HCV) who initiate direct-acting antivirals (DAAs) for HCV treatment may have to switch antiretroviral therapy (ART) because of drug interactions. ART switches can negatively affect quality of life, increase HIV symptom burden, and delay HCV therapy. Approaches to identify ART/DAA drug interactions that minimize the impact of switching ART are urgently needed. Nurses can lead the way in addressing this new and major need. We provide a guide for registered nurses and nurse practitioners who care for patients coinfected with HIV and HCV to identify HIV/HCV drug interactions and manage ART/DAA coadministration when needed.
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http://dx.doi.org/10.1097/JNC.0000000000000144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047613PMC
September 2020

Unreported alcohol use was common but did not impact hepatitis C cure in HIV-infected persons who use drugs.

J Viral Hepat 2020 05 7;27(5):476-483. Epub 2020 Jan 7.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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.
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http://dx.doi.org/10.1111/jvh.13251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890377PMC
May 2020

Nurse case management to improve the hepatitis C care continuum in HIV co-infection: Results of a randomized controlled trial.

J Viral Hepat 2020 04 9;27(4):376-386. Epub 2019 Dec 9.

Johns Hopkins University School of Nursing, Baltimore, MD, USA.

The opportunity to eliminate hepatitis C virus (HCV) is at hand, but challenges remain that negatively influence progress through the care continuum, particularly for persons co-infected with HIV who are not well engaged in care. We conducted a randomized controlled trial to test the effect of nurse case management (NCM) on the HCV continuum among adults co-infected with HIV compared to usual care (UC). Primary outcomes included linkage to HCV care (attendance at an HCV practice appointment within 60 days) and time to direct-acting antiviral (DAA) initiation (censored at 6 months). Sixty-eight participants were enrolled (NCM n = 35; UC n = 33). Participants were 81% Black/African American, 85% received Medicaid, 46% reported illicit drug use, 41% alcohol use, and 43% had an undetectable HIV viral load. At day 60, 47% of NCM participants linked to HCV care compared to 25% of UC participants (P = .031; 95% confidence bound for difference, 3.2%-40.9%). Few participants initiated DAAs (12% NCM; 25% UC). There was no significant difference in mean time to treatment initiation (NCM = 86 days; UC = 110 days; P = .192). Engagement in HCV care across the continuum was associated with drinking alcohol, knowing someone who cured HCV and having a higher CD4 cell count (P < .05). Our results support provision of NCM as a successful strategy to link persons co-infected with HIV to HCV care, but interventions should persist beyond linkage to care. Capitalizing on social networks, treatment pathways for patients who drink alcohol, and integrated substance use services may help improve the HCV care continuum.
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http://dx.doi.org/10.1111/jvh.13241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080578PMC
April 2020