Hospitalization is a missed opportunity for HIV screening, pre-exposure prophylaxis, and treatment.

BACKGROUND: Hospitalization is a "reachable moment" for people who inject drugs (PWID), but preventive care including HIV testing, prevention and treatment is rarely offered within inpatient settings. METHODS: We conducted a multisite, retrospective cohort study of patients with opioid use disorder with infectious complications of injection drug use hospitalized between 1/1/2018-12/31/2018. We evaluated HIV care continuum outcomes using descriptive statistics and hypothesis tests for intergroup differences. RESULTS: 322 patients were included. Of 300 patients without known HIV, only 2 had a documented discussion of PrEP, while only 1 was prescribed PrEP on discharge. Among the 22 people with HIV (PWH), only 13 (59%) had a viral load collected during admission of whom all were viremic and 10 (45%) were successfully linked to care post-discharge. Rates of readmission, Medicaid or uninsured status, and unstable housing were high in both groups. DISCUSSION: We observed poor provision of HIV testing, PrEP and other HIV services for hospitalized PWID across multiple U.S. medical centers. Future initiatives should focus on providing this group with comprehensive HIV testing and treatment services through a status neutral approach.

Use of nonstigmatizing language is associated with improved outcomes in hospitalized people who inject drugs.

BACKGROUND: Stigma surrounding opioid use disorder (OUD) is a barrier to treatment. The use of stigmatizing language may be evidence of negative views toward patients. OBJECTIVE: We aimed to identify associations between language and clinical outcomes in patients admitted for infectious complications of OUD. DESIGNS: We performed a retrospective medical record review. SETTINGS AND PARTICIPANTS: Four U.S. academic health systems. Participants were patients with OUD admitted for infectious complications of injection opioid use from January 1, 2018, to December 31, 2018, identified through international classification of diseases, 10th revision codes consistent with OUD and acute bacterial/fungal infection. MAIN OUTCOME AND MEASURES: Discharge summaries were reviewed for language, specifically: abuse, addiction, dependence, misuse, use disorder, intravenous drug use, and others. Binary outcomes including medication for OUD, planned discharge, naloxone provision, and an OUD treatment plan were evaluated using logistic regressions and admission duration was evaluated using Gamma regression. RESULTS: A total of 1285 records were reviewed and 328 met inclusion criteria. Of those, 191 (58%) were male, with a median age of 38 years. The most common term was "abuse" (219, 67%), whereas "use disorder" was recorded in 75 (23%) records. Having "use disorder" in the discharge summary was associated with increased odds of having a documented plan for ongoing OUD treatment (adjusted odds ratio [AOR]: 4.11, 95% confidence interval [CI]: 1.89-8.93) and having a documented plan for addiction-specific follow-up care (AOR: 2.31, 95% CI: 1.30-4.09). CONCLUSIONS: Stigmatizing language was common in this study of patients hospitalized for infectious complications of OUD. Best-practice language was uncommon, but when used was associated with increased odds of addiction treatment and specialty care referrals.

Undertreatment of opioid use disorder in patients hospitalized with injection drug use-associated infections.

OBJECTIVE: To evaluate the association between medication for opioid use disorder (MOUD) initiation and addiction consultation and outcomes for patients hospitalized with infectious complications of injecting opioids. METHOD: This was a retrospective cohort study performed at four academic medical centers in the United States. The participants were patients who had been hospitalized with infectious complications of injecting opioids in 2018. Three hundred and twenty-two patients were included and their individual patient records were manually reviewed to identify inpatient receipt of medication for opioid use disorder (MOUD), initiation of MOUD, and addiction consultation. The main outcomes of interest were premature discharge, MOUD on discharge, linkage to outpatient MOUD, one-year readmission and death. RESULTS: Three hundred and twenty-two patients were predominately male (59%), white (66%), and median age 38 years, with 36% unstably housed, and 30% uninsured. One hundred and forty-five (45%) patients received MOUD during hospitalization, including only 65 (28%) patients not on baseline MOUD. Discharge was premature for 64 (20%) patients. In the year following discharge, 27 (9%) patients were linked to MOUD, and 159 (50%) patients had at least one readmission. Being on MOUD during hospitalization was significantly associated with higher odds of planned discharge [odds ratio (OR) 3.87, P  < 0.0001], MOUD on discharge (OR 129.7, P  < 0.0001), and linkage to outpatient MOUD (OR 1.25, P  < 0.0001), however, was not associated with readmission. Study limitations were the retrospective nature of the study, so post-discharge data are likely underestimated. CONCLUSION: There was dramatic undertreatment with MOUD from inpatient admission to outpatient linkage, and high rates of premature discharge and readmission. Engagement in addiction care during hospitalization is a critical first step in improving the care continuum for individuals with opioid use disorder; however, additional interventions may be needed to impact long-term outcomes like readmission.

Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 virus-specific cytotoxic T-cell lymphocytes (vCTLs) could provide a promising modality in COVID-19 treatment. We aimed to screen, manufacture, and characterize SARS-CoV-2-vCTLs generated from convalescent COVID-19 donors using the CliniMACS Cytokine Capture System (CCS). METHODS: Donor screening was done by stimulation of convalescent COVID-19 donor peripheral blood mononuclear cells with viral peptides and identification of interferonγ (IFN-γ)+ CD4 and CD8 T cells using flow cytometry. Clinical-grade SARS-CoV-2-vCTLs were manufactured using the CliniMACS CCS. The enriched SARS-CoV-2-vCTLs were characterized by T-cell receptor sequencing, mass cytometry, and transcriptome analysis. RESULTS: Of the convalescent donor blood samples, 93% passed the screening criteria for clinical manufacture. Three validation runs resulted in enriched T cells that were 79% (standard error of the mean 21%) IFN-γ+ T cells. SARS-CoV-2-vCTLs displayed a highly diverse T-cell receptor repertoire with enhancement of both memory CD8 and CD4 T cells, especially in CD8 TEM, CD4 TCM, and CD4 TEMRA cell subsets. SARS-CoV-2-vCTLs were polyfunctional with increased gene expression in T-cell function, interleukin, pathogen defense, and tumor necrosis factor superfamily pathways. CONCLUSIONS: Highly functional SARS-CoV-2-vCTLs can be rapidly generated by direct cytokine enrichment (12 hours) from convalescent donors. CLINICAL TRIALS REGISTRATION: NCT04896606.

Hepatitis C cure and medications for opioid use disorder improve health-related quality of life in patients with opioid use disorder actively engaged in substance use.

BACKGROUND: This study aims to determine whether Hepatitis C (HCV) treatment improves health-related quality of life (HRQL) in patients with opioid use disorder (OUD) actively engaged in substance use, and which variables are associated with improving HRQL in patients with OUD during HCV treatment. METHODS: Data are from a prospective, open-label, observational study of 198 patients with OUD or opioid misuse within 1 year of study enrollment who received HCV treatment with the primary endpoint of Sustained Virologic Response (SVR). HRQL was assessed using the Hepatitis C Virus Patient Reported Outcomes (HCV-PRO) survey, with higher scores denoting better HRQL. HCV-PRO surveys were conducted at Day 0, Week 12, and Week 24. A mixed-effects model investigated which variables were associated with changing HCV-PRO scores from Day 0 to Week 24. RESULTS: Patients had a median age of 57 and were predominantly male (68.2%) and Black (83.3%). Most reported daily-or-more drug use (58.6%) and injection drug use (IDU) (75.8%). Mean HCV-PRO scores at Day 0 and Week 24 were 64.0 and 72.9, respectively. HCV-PRO scores at Week 24 improved compared with scores at Day 0 (8.7; p<0.001). Achieving SVR (10.4; p<0.001) and receiving medications for OUD (MOUD) at Week 24 (9.5; p<0.001) were associated with improving HCV-PRO scores. HCV-PRO scores increased at Week 24 for patients who experienced no decline in IDU frequency (8.1; p<0.001) or had a UDS positive for opioids (8.0; p<0.001) or cocaine (7.5; p=0.003) at Week 24. CONCLUSION: Patients with OUD actively engaged in substance use experience improvement in HRQL from HCV cure unaffected by ongoing substance use. Interventions to promote HCV cure and MOUD engagement could improve HRQL for patients with OUD.

"I got so much on my plate": Understanding care discontinuity for HIV and HCV among formerly incarcerated persons.

OBJECTIVE: To explore barriers to care continuity among formerly incarcerated persons with HIV and/or hepatitis C. DATA SOURCES AND STUDY SETTING: We draw on data from semi-structured interviews conducted in 2018-2019 with 30 formerly incarcerated persons and 10 care providers. Data were collected across two clinics in Baltimore, Maryland, and Washington, D.C. STUDY DESIGN: We recruited participants using a combination of nonprobability sampling techniques. Participants completed closed-ended questionnaires and took part in semi-structured interviews related to treatment barriers and incentives. DATA COLLECTION/EXTRACTION METHODS: Interviews were transcribed using Express Scribe software and transcriptions were open coded using NVivo 12 software. An iterative process was used to relate and build upon emergent themes in interviews. PRINCIPAL FINDINGS: Our study illuminates both internal and external barriers to care continuity. The most common external barriers were system navigation and housing instability. Internal barriers consisted of overlapping issues related to mental health, substance use, and feelings of shame and/or denial. CONCLUSION: An overarching theme is that formerly incarcerated persons with HIV and/or HCV are grappling with numerous challenges that can threaten their health and health care. These barriers are cumulative, intersecting, and reciprocal.

PrEP Indications and PrEP Knowledge, Access, and Interest Among Individuals With HCV.

Background: Individuals with hepatitis C (HCV) represent a population that may benefit from pre-exposure prophylaxis (PrEP), given the overlapping risk factors and transmission networks of HCV and HIV. This analysis assesses the prevalence of PrEP indications among individuals with HCV monoinfection and PrEP awareness, interest, and access in this population. Methods: GRAVITY was an observational study for the collection of epidemiologic data from individuals with HCV and/or HIV in Washington DC and Baltimore, with the present analysis limited to HCV-monoinfected patients. The prevalence of PrEP indications was determined using epidemiologic survey responses. Bivariate and multivariable analyses assessed for associations between PrEP indications and PrEP awareness, access, and interest. Results: Among 314 HCV-monoinfected participants, 109 (35%) had an indication for PrEP. Forty-eight (44%) had a drug use indication alone, 40 (37%) had a sexual indication alone, and 21 (19%) had both drug use and sexual indications. Eighty-five (27%) participants had heard of PrEP, 32 (10%) had been offered PrEP by a provider, 114 (38%) were interested or maybe interested in PrEP, and 6 (2%) were currently taking PrEP. On bivariate analysis, PrEP awareness was significantly associated with study site (P < .0001), race (P = .0003), age (P < .0001), and sexual PrEP indication (P = .04). However, only study site remained significant (P = .0002) on regression analysis. Conclusions: Though indications for PrEP were prevalent among individuals with HCV in this cohort, most patients were unaware of PrEP, had never been offered PrEP, and were not using PrEP. These data support the need for improved PrEP implementation among people with HCV.

Suboptimal Uptake, Retention, and Adherence of Daily Oral Prexposure Prophylaxis Among People With Opioid Use Disorder Receiving Hepatitis C Virus Treatment.

BACKGROUND: Daily oral preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) prevents human immunodeficiency (HIV) among people who inject drugs (PWID). Despite rising HIV incidence and injection drug use (IDU), PrEP use remains low and there is limited research about uptake, adherence, and retention among PWID. METHODS: The ANCHOR investigation evaluated a community-based care model collocating hepatitis C virus (HCV) treatment, medication for opioid use disorder (OUD), and PrEP in individuals in Washington, DC, and Baltimore, Maryland. PrEP counseling was conducted from HCV treatment day 0 until week 24. Subjects could start any time during this window, were followed for 48 weeks, and were assessed for adherence by self-report and dried blood spot TDF analysis. RESULTS: One hundred ninety-eight participants were enrolled, of whom 185 (93%) were HIV negative. Twenty-nine individuals (15.7% of HIV-negative cohort) initiated PrEP. One hundred sixteen participants (62.7%) met 2014 Centers for Disease Control and Prevention (CDC) PrEP criteria due to IDU (82 [44.3%]), sex (9 [4.9%]), or both practices (25 [13.5%]). Providers recommended PrEP to 94 individuals (50.8%), and recommendation was associated with PrEP uptake. Median treatment duration was 104 days (interquartile range, 28-276 days), with 8 participants retained through week 48. Adherence was variable over time by self-report and declined by TDF analysis. No HIV seroconversions occurred. CONCLUSIONS: This cohort of people with HCV and OUD experienced low uptake of PrEP despite the majority meeting CDC criteria. High rates of disruption and discontinuation, compounded by variable adherence, made TDF/FTC a suboptimal prevention strategy. Emerging modalities like long-acting formulations may address these barriers, but PWID have been excluded from their development to date.

Initiation of Low-threshold Buprenorphine in Nontreatment Seeking Patients With Opioid Use Disorder Engaged in Hepatitis C Treatment.

OBJECTIVE: The ANCHOR program offered buprenorphine treatment to people who inject drugs engaged in hepatitis C (HCV) treatment at a Washington, DC harm reduction organization. This analysis describes the program model and outcomes of the opioid care continuum at 1 year. METHODS: Primary outcomes were initiation of buprenorphine and retention in care, defined by an active buprenorphine prescription at given time points. Secondary outcomes included treatment interruptions, reasons for treatment noninitiation and termination, buprenorphine and opiate use, and HIV risk behaviors. Buprenorphine and opiate use were measured by urine toxicology screens and HIV risk behavior was quantified using a validated survey. RESULTS: Of 67 patients receiving HCV treatment not on opioid agonist therapy at baseline, 96% (n = 64) were interested and 73% (n = 49) initiated buprenorphine. Retention was 82% (n = 40), 65% (n = 32), and 59% (n = 29) at months 1, 6, and 12, respectively. Retention at 12 months was associated with self-reported engagement in routine medical care (P < 0.01), but was not associated with gender, stable housing, past opioid agonist therapy, or past overdose. Among retained patients, urine screens positive for opioids were 73% (n = 29), 56% (n = 18), and 79% (n = 23) at months 1, 6, and 12. There was a significant mean decrease in HIV risk-taking behavior scores over the treatment period, primarily driven by reduced injection frequency. CONCLUSIONS: Patients engaged in HCV treatment at a harm reduction organization showed a high rate of initiation of buprenorphine treatment, with retention comparable to other treatment settings. Although most patients continued using opioids on treatment, there was a reduced frequency of injection drug use, a significant driver of OUD-related risk. These data support the use of low-threshold buprenorphine access alongside HCV treatment to reduce morbidity and mortality in people with OUD.

Expanding the Evidence on Integrated Opioid Use Disorder and Infectious Disease Care.

Low-barrier to access programs has emerged as a way to overcome the significant hurdles associated with buprenorphine initiation. However, there has been limited research evaluating services set in low-barrier programs outside of buprenorphine. In this issue of the Journal of Addiction Medicine, Harvey and colleagues evaluate a sexually transmitted and blood-borne infection screening protocol implemented in a low-barrier access program in Boston, Massachusetts. The data supports that infection protocols can be efficiently implemented in the low-barrier setting, yielding high rates of diagnosis, and the potential for decentralized models of treatment.

The Effect of GS-548351 on the Pharmacokinetics of Midazolam Following Multiple Doses of ANS-6637 in Healthy Adults.

ANS-6637, a pro-drug of GS-548351, is a selective, reversible inhibitor of aldehyde dehydrogenase isoform 2 under development as an anticraving agent for the treatment of substance use disorders. In vitro testing indicates that GS-548351 is an inhibitor and inducer of cytochrome P450 family 3, subfamily A (CYP3A). In this phase 1 single-center, open-label, fixed-sequence drug-drug interaction study we assessed the impact of steady-state GS-548351 on single-dose pharmacokinetics of midazolam, an index substrate for CYP3A. Twelve healthy volunteers received 600 mg of ANS-6637 by mouth daily from study days 3 to 8 and a single 5-mg oral dose of midazolam on days 1 and 8. Pharmacokinetic samples were collected over 24 hours on days 1 and 8, then analyzed using liquid chromatography-tandem mass spectrometry. The prespecified no-effect range for the 90% confidence interval (CI) of the geometric mean ratio (GMR) of midazolam coadministered with ANS-6637 (day 8) compared with midazolam alone (day 1) was 0.7-1.43. There was an increase in midazolam AUC0-∞ (GMR [90%CI]) that was within the no-effect range (1.26 [1.12-1.425]) and an increase in midazolam Cmax that was outside the range (1.22 [1.03-1.45]). The AUC0-∞ (1.08 [0.91-1.27]) and Cmax (0.95 [0.75-1.2]) of 1-hydroxymidazolam, the primary metabolite of midazolam, were also within the no-effect range. A single grade 3 adverse event (alanine aminotransferase elevation) was identified and resolved following discontinuation of the study drug. Overall, multidose ANS-6637 was well tolerated and did not alter the PK of midazolam beyond a small increase in AUC0-∞ that is unlikely to be clinically significant.

Concurrent Initiation of Hepatitis C and Opioid Use Disorder Treatment in People Who Inject Drugs.

BACKGROUND: People who inject drugs have a high prevalence of hepatitis C virus (HCV) and significant disease associated with drug use; however, HCV treatment often occurs in absence of interventions to address opioid use disorder and drug use-related harms. The impact of concurrent initiation of opioid agonist therapy (OAT) on HCV treatment and drug use outcomes is unknown. METHODS: In this prospective, open-label, observational trial at a harm reduction organization's drop-in center in Washington, DC, 100 patients with chronic HCV infection, opioid use disorder, and ongoing injection drug use were treated with sofosbuvir-velpatasvir for 12-weeks and offered buprenorphine initiation. The primary end point was sustained virologic response (SVR), and secondary end points included uptake of and retention in OAT, change in risk behavior, and determinants of SVR. RESULTS: Eighty-two patients (82%) achieved SVR, which was not associated with baseline OAT status (P = .33), on-treatment drug use (P >.99), or imperfect daily adherence (P = .35) but was significantly associated with completing 2 or more 28-pill bottles of sofosbuvir-velpatasvir (P < .001) and receiving OAT at week 24 (P = .01). Of 67 patients not already receiving OAT at baseline, 53 (79%) started OAT. At week 24, 68 (68%) patients were receiving OAT. Receipt of OAT was associated with fewer opiate-positive urine drug screens (P = .003), lower human immunodeficiency virus risk-taking behavior scores (P < .001), and lower rates of opioid overdose (P = .04). CONCLUSIONS: The Novel Model of Hepatitis C Treatment as an Anchor to Prevent HIV, Initiate Opioid Agonist Therapy, and Reduce Risky Behavior study demonstrates high uptake of buprenorphine collocated with HCV treatment, and it shows that concurrent initiation of OAT with HCV treatment can result in high rates of SVR while reducing risks associated with drug use. CLINICAL TRIALS REGISTRATION: NCT03221309.

Long-term changes in hepatic fibrosis following hepatitis C viral clearance in patients with and without HIV.

BACKGROUND: While acute changes in hepatic fibrosis are recognized shortly after achieving sustained virological response (SVR) using direct-acting antiviral therapies, long-term outcomes for the growing population of successfully treated patients with HCV remain uncertain. The aim of this study is to characterize long-term changes in fibrosis following SVR in patients with and without HIV and to identify potential factors associated with progression or regression of fibrosis. METHODS: We completed a prospective longitudinal study of 162 subjects with HCV (34% HIV-coinfected) with pre-treatment fibrosis stage determined by liver biopsy and post-SVR transient elastography. Progression of fibrosis was defined as a two-stage or greater increase in fibrosis, while regression was defined as a two-stage or greater decrease at last follow-up. The median duration of follow-up was 4.1 years. RESULTS: Fibrosis progression occurred in 4% of subjects while regression occurred in 7% and 89% were stable and did not differ by HIV coinfection. Fibrosis progression was associated with increased body mass index (BMI), hepatic steatosis and smoking pack-years. In a multivariable logistic regression, HIV coinfection (P=0.009), lower steatosis score (P<0.05) and lower smoking pack-years (P=0.0007) were associated with a lower fibrosis score at last follow-up. CONCLUSIONS: We identify potentially important relationships between BMI, hepatic steatosis and smoking, and changes in hepatic fibrosis post-SVR in patients with and without HIV coinfection. Attention to modifiable risk factors such as body weight and smoking may reduce the risk of liver disease progression in the growing population of successfully treated chronic HCV patients.

A pilot study of safety and efficacy of HCV retreatment with sofosbuvir/velpatasvir/voxilaprevir in patients with or without HIV (RESOLVE STUDY).

BACKGROUND & AIMS: Cure rates in response to retreatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) are high, but this regimen has not been studied in patients with a history of poor adherence or treatment interruption, nor in patients with HIV/HCV coinfection. Herein, we aimed to assess the safety and efficacy of this combination in patients with genotype 1 HCV infection who had relapsed following combination direct-acting antiviral (DAA) therapy, regardless of HIV infection or previous treatment course. METHODS: The RESOLVE study was a multicenter, open-label, phase IIb study investigating the safety, tolerability and efficacy of SOF/VEL/VOX in 77 patients with virologic rebound following combination DAA therapy. Efficacy was defined as HCV RNA below the lower limit of detection 12 weeks after the end of treatment (SVR12), while safety endpoints included the incidence of grade 3 and 4 adverse events (AEs) following treatment, and the proportion of patients who stopped treatment prematurely due to AEs. RESULTS: In an intent-to-treat analysis, 70/77 (90.9%, 95% CI 82.1-95.8%) patients achieved SVR12, including 14/17 (82.4%) HIV coinfected participants and 18/22 (81.8%) of those with previous non-completion of DAA therapy. In an analysis of all patients who completed 12 weeks of study medication, 70/71 patients (99%) achieved SVR12. One patient experienced a grade 3 AE, and 4 experienced a grade 4 AE, all unrelated to study participation. Reported AEs were similar in HIV-coinfected patients, and patients receiving dolutegravir-based antiretroviral treatment experienced no clinically significant increases in aminotransferases. CONCLUSION: Retreatment with 12 weeks of SOF/VEL/VOX was safe and effective in patients with relapsed HCV following initial combination DAA-based treatment. Treatment response was not affected by HIV coinfection or previous treatment course. LAY SUMMARY: Twelve weeks of the combination of direct-acting antivirals (SOF/VEL/VOX) was safe and effective in patients with relapsed hepatitis C virus infection who had previously received combination therapy with direct-acting antivirals. Treatment response was not diminished by HIV coinfection, or non-completion of previous direct-acting antiviral-based therapy.

High Morbidity and Mortality Among Patients With Sentinel Admission for Injection Drug Use-Related Infective Endocarditis.

BACKGROUND: Hospitalizations for individuals with injection drug use-related infective endocarditis (IDU-IE) represent an increasing portion of all patients with endocarditis. This study describes the evolving trends in demographics, clinical characteristics, rates of surgical intervention, and mortality among patients hospitalized with IE, comparing those with and without injection drug use. METHODS: This is a retrospective cohort study of patients admitted between January 1, 2007 to June 30, 2015 at a tertiary care center in Boston, Massachusetts. Endocarditis was defined by International Classification of Diseases, Ninth Revision code and verified by the modified Duke Criteria for IE. The clinical characteristics, microbiology, site of infection, complications of IE, and outcome were all abstracted by chart review. Rates of surgical consultation and surgical intervention within 90 days of admission were obtained, and assessment of surgical risk calculated was by EuroSCORE II (euroscore.org/calc). Subsequent hospitalizations for all causes were also reviewed. RESULTS: Injection drug use-related infective endocarditis occurred in younger patients with lower rates of diabetes, renal dysfunction, and prior cardiothoracic (CT) surgery than those without IDU. Injection drug use-related infective endocarditis was associated with higher rates of complications, CT surgery consultation, and surgery within 90 days for absolute surgical indication. Readmissions for endocarditis occurred in 20% of IDU-IE patients and 9% of those with non-IDU IE. All-cause 1-year mortality rates were similar (IDU-IE 16%, non-IDU IE 13%; P = .58). CONCLUSIONS: Despite younger age, fewer medical comorbidities, and fewer prior cardiac surgeries, all-cause 1-year mortality was similar for patients after sentinel admission for IDU-IE compared with non-IDU IE. Interventions in the acute hospital setting and after discharge are needed to support patients with IDU-IE, focusing on harm reduction and treatment of addiction to reduce the unexpectedly high mortality of this young population.

Opioids and Infectious Diseases: A Converging Public Health Crisis.

A converging public health crisis is emerging because the opioid epidemic is fueling a surge in infectious diseases, such as human immunodeficiency virus infection with or without AIDS, the viral hepatitides, infective endocarditis, and skin and soft-tissue infections. An integrated strategy is needed to tailor preventive and therapeutic approaches toward infectious diseases in people who misuse and/or are addicted to opioids and to concurrently address the underlying predisposing factor for the infections-opioid use disorder. This commentary highlights the unique and complementary roles that the infectious diseases and substance use disorder communities can play in addressing this crisis of dual public health concerns.

Testosterone in Men With Chronic Hepatitis C Infection and After Hepatitis C Viral Clearance.

BACKGROUND: Hepatitis C virus (HCV) and hepatic dysfunction are associated with low total and free testosterone (TT and FT) and high sex hormone-binding globulin (SHBG). However, little is known about changes in testosterone following successful HCV treatment. METHODS: We evaluated testosterone levels and the prevalence of low testosterone in a cohort of 327 men with chronic HCV infection (human immunodeficiency virus [HIV] coinfection = 150) and in a subset of 85 men with testosterone levels obtained pre-HCV treatment and after sustained virologic response (SVR). Median follow-up was 36 months. RESULTS: Participants with active HCV at baseline had higher TT (P < .0001) and SHBG (P < .0001) compared with participants who had achieved SVR, whereas FT did not differ. Low TT (<10.4 nmol/L) was more prevalent in participants with SVR compared with active HCV (P = .002); however, low FT (<0.1735 nmol/L) was common (50% active HCV, 43% SVR) and did not different between groups. For participants with longitudinal determinations, TT and SHBG decreased significantly (P < .0001) while FT remained unchanged post-SVR. Low FT persisted after SVR (pre-treatment 58%, post-SVR 54%, P = .72). HIV status and change in aspartate aminotrasferase-to-platelet ratio were significant independent predictors of change in FT following SVR. CONCLUSIONS: During active HCV infection, testosterone deficiency may be masked due to elevated SHBG. Despite improvements in SHBG following SVR, low FT was common and persisted after HCV clearance, indicating the need for enhanced awareness and screening using estimates of FT following successful treatment of chronic HCV. CLINICAL TRIALS REGISTRATION: NCT01350648.

Multitarget Direct-Acting Antiviral Therapy Is Associated With Superior Immunologic Recovery in Patients Coinfected With Human Immunodeficiency Virus and Hepatitis C Virus.

Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have higher levels of immune activation, impaired antigen-specific responses, and accelerated fibrogenesis compared to patients monoinfected with HCV. Whether different direct-acting antiviral (DAA) combinations have differential effects on immunophenotypes and functions following successful HCV therapy remain unknown. Therefore, we aimed to assess the peripheral T-cell immunophenotypes and functions in patients coinfected with HIV/HCV who were successfully treated with combination DAA treatment regimens. We analyzed peripheral blood mononuclear cells (PBMCs) at baseline and at the time of sustained viral response (SVR) from subjects treated with three different combination DAA regimens: daclatasvir (DCV) and asunaprevir (ASV) for 24 weeks (CONQUER 2-DAA), DCV/ASV/beclabuvir (BCV) for 12 weeks (CONQUER 3-DAA), and sofosbuvir (SOF) and ledipasvir (LDV) for 12 weeks (ERADICATE study). We used flow cytometry to assess T-cell phenotypes (activation and exhaustion) and HCV-specific T-cell functions (cytokine secretion and cytotoxicity). Statistical analyses were conducted using the Wilcoxon matched-pairs signed-rank test with P < 0.05 considered significant. Overall, there was an improvement in T-cell exhaustion markers, a decrease in T-cell activation, an increase in the effector memory population, and improved T-cell function after achieving SVR, with the largest effects noted with CONQUER 3-DAA treatment. Conclusion: Treatment with DCV/ASV/BCV in patients coinfected with HIV/HCV resulted in greater restoration of the T-cell impairments and perturbations associated with HIV/HCV coinfection to an extent that was greater than that observed in either two-drug regimens. We showed that different DAA-based therapies have different immunologic outcomes after successful HCV treatment in patients coinfected with HIV/HCV. This information will be beneficial for providers when selecting the regimens for patients coinfected with HIV/HCV.