Publications by authors named "David L Wyles"

Background: Hepatitis C virus (HCV) continues to cause significant morbidity and mortality within the US, and disproportionately impacts those involved with the criminal justice system. Despite this, knowledge and attitudes regarding HCV treatment among adults on probation have not been well studied. We conducted a cross-sectional survey of adults on probation accessing on-site HCV testing and linkage services at the adult probation department in Denver, Colorado.

View Article and Find Full Text PDF

Background: Long-term outcome data after hepatitis C virus (HCV) treatment are limited, particularly for comparisons between persons with and without HIV.

Methods: A5320 was a prospective cohort study that enrolled participants within 12 months of completing HCV DAA therapy, with or without sustained virologic response (SVR). The primary end point was composite: time to death or development of a targeted diagnosis.

View Article and Find Full Text PDF

Background: Hepatitis C (HCV) poses a major public health problem in the USA. While early identification is a critical priority, subsequent linkage to a treatment specialist is a crucial step that bridges diagnosed patients to treatment, cure, and prevention of ongoing transmission. Emergency departments (EDs) serve as an important clinical setting for HCV screening, although optimal methods of linkage-to-care for HCV-diagnosed individuals remain unknown.

View Article and Find Full Text PDF

Background: Periodic surveillance of the hepatitis C virus (HCV) care cascade is important for tracking progress toward HCV elimination goals, identifying gaps in care, and prioritizing resource allocation. In the pre-direct-acting antiviral (DAA) era, it was estimated that 50% of HCV-infected individuals were diagnosed and that 16% had been prescribed interferon-based therapy. Since then, few studies utilizing nationally representative data from the DAA era have been conducted in the United States.

View Article and Find Full Text PDF

Background: Despite constituting the largest segment of the correctional population, individuals on court-ordered probation remain largely unstudied with respect to hepatitis C virus (HCV) testing and linkage-to-care. We conducted a retrospective, descriptive analysis to estimate prevalence of diagnosed HCV and the subsequent HCV care cascade among a cohort of individuals enrolled in an adult probation program over a 25-month period in Denver, Colorado.

Methods: We utilized probabilistic matching with first and last name, sex, and birthdate to identify individuals enrolled in probation between July 1, 2016 and July 30, 2018 who had a medical record at the participating safety-net healthcare institution as of December 31, 2019.

View Article and Find Full Text PDF

Direct-acting antivirals (DAAs) achieve high hepatitis C virus (HCV) cure rates and are forgiving to missed doses, but adherence-efficacy relationships have not been well defined. Traditional adherence measures (e.g.

View Article and Find Full Text PDF

Background: Early identification of HCV is a critical health priority, especially now that treatment options are available to limit further transmission and provide cure before long-term sequelae develop. Emergency departments (EDs) are important clinical settings for HCV screening given that EDs serve many at-risk patients who do not access other forms of healthcare. In this article, we describe the rationale and design of The Determining Effective Testing in Emergency Departments and Care Coordination on Treatment Outcomes (DETECT) for Hepatitis C (Hep C) Screening Trial.

View Article and Find Full Text PDF

Background: Despite constituting the largest segment of the correctional population, individuals on probation remain largely unstudied with respect to hepatitis C virus (HCV) testing and linkage to care. We implemented an HCV testing and patient navigation program at an adult probation department.

Methods: Adults were tested at a local probation department with a rapid point-of-care HCV antibody (Ab) assay followed by a laboratory-based HCV ribonucleic acid (RNA) assay if anti-HCV positive.

View Article and Find Full Text PDF

Final results from the long-term Viral Hepatitis C Infection Long-term Cohort Study (V-HICS) found low rates of hepatitis C virus (HCV) recurrence after direct-acting antiviral therapy in both HCV/human immunodeficiency virus (HIV)-coinfected (0.67/100 person-years) and HCV-infected (0.2/100 person-years) groups with >500 person-years of follow-up.

View Article and Find Full Text PDF

Background: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19.

Methods: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA).

View Article and Find Full Text PDF

At the 2021 Conference on Retroviruses and Opportunistic Infections, there was a focus on progress toward hepatitis C virus (HCV) microelimination in geographic regions and targeted populations. HCV elimination is facilitated by well-tolerated, highly effective HCV treatment that requires essentially no on-treatment monitoring in most patients, as highlighted by the MINMON (Minimal Monitoring Study or A5360) study, and that should be increasingly available to children with new data supporting feasible treatment in younger patients. Challenges to HCV elimination include HCV reinfection via sexual exposure in men who have sex with men (MSM) and continued barriers to diagnosis and access to HCV treatment.

View Article and Find Full Text PDF

Twenty-seven patients receiving prolonged inpatient antibiotic therapy for a serious bacterial infection received a single dose of dalbavancin 7-10 days before the planned end date to facilitate earlier hospital discharge. Eighty-one percent met criteria for clinical success, 7% experienced a potential adverse event, and 182 hospital days were averted.

View Article and Find Full Text PDF

Background: Ledipasvir/sofosbuvir increases tenofovir plasma exposures by up to 98% with tenofovir disoproxil fumarate (TDF), and exposures are highest with boosted PIs. There are currently no data on the combined use of the newer tenofovir prodrug, tenofovir alafenamide (TAF), boosted PIs and ledipasvir/sofosbuvir.

Objectives: To compare the plasma and intracellular pharmacokinetics and renal safety of TAF with ledipasvir/sofosbuvir when co-administered with boosted PIs.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Background: Direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) result in initial cure rates of 95% to 99% and re-treatment cure rates of 95%. Nevertheless, given the sheer magnitude of infected persons, some will ultimately fail multiple DAA therapies, and re-treatment of these persons has not been adequately studied.

Methods: We evaluated treated an HIV-infected man with cirrhosis from genotype 1b HCV who had failed 3 DAA regimens.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Aims: AIDS Clinical Trials Group study A5334s evaluated the pharmacokinetics of raltegravir before and during combined administration of ombitasvir, paritaprevir/ritonavir, plus dasabuvir (OBV/PTV/r + DSV) and weight-based ribavirin in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected adults. The pharmacokinetics of OBV/PTV/r + DSV during raltegravir coadministration were also characterized.

Methods: Adults living with HIV/HCV coinfection receiving steady-state raltegravir (400 mg twice daily) with 2 nucleos(t)ide analogues were enrolled.

View Article and Find Full Text PDF

Hepatitis B virus (HBV) coinfection is common in persons with human immunodeficiency virus (HIV) infection, contributing significantly to morbidity and mortality. Many currently used HIV antiretroviral therapy (ART) regimens provide potent anti-HBV activity and it is recommended that HBV-HIV coinfected persons be treated with ART regimens containing tenofovir. ART has multiple benefits, including increasing rates of HBV clearance after initial infection and potent suppression of HBV DNA in chronic infection.

View Article and Find Full Text PDF

At the 2019 Conference on Retroviruses and Opportunistic Infections (CROI), there was a major focus on hepatitis C virus (HCV) elimination and improving each component of the hepatitis C care cascade. Many interventions showed promising improvements in diagnosis and linkage to care. Settings with robust access to direct-acting antivirals (DAAs) continue to demonstrate the role of HCV treatment as prevention.

View Article and Find Full Text PDF

Background: We evaluated the impact of opioid substitution therapy (OST) on the completion, adherence, efficacy, and safety of the 3-direct-acting antiviral regimen of ombitasvir, paritaprevir (identified by AbbVie and Enanta) co-dosed with ritonavir, and dasabuvir ± ribavirin among patients infected with hepatitis C virus (HCV) genotype (GT) 1, with or without compensated cirrhosis.

Methods: Data were pooled from GT1-infected patients enrolled in 12 phase II/III/IIIb clinical trials and categorized by use of OST. Patients with ongoing drug use were excluded.

View Article and Find Full Text PDF

Glecaprevir coformulated with pibrentasvir (G/P) is approved to treat hepatitis C virus (HCV) infection and was highly efficacious in phase 2 and 3 studies. Treating HCV genotype (GT) 3 infection remains a priority, as these patients are harder to cure and at a greater risk for liver steatosis, fibrosis progression and hepatocellular carcinoma. Data were pooled from five phase 2 or 3 trials that evaluated 8-, 12- and 16-week G/P in patients with chronic HCV GT3 infection.

View Article and Find Full Text PDF