HCV universal EHR prompt successfully increases screening, highlights potential disparities.

BACKGROUND & OBJECTIVES: Screening for hepatitis C virus is the first critical decision point for preventing morbidity and mortality from HCV cirrhosis and hepatocellular carcinoma and will ultimately contribute to global elimination of a curable disease. This study aims to portray the changes over time in HCV screening rates and the screened population characteristics following the 2020 implementation of an electronic health record (EHR) alert for universal screening in the outpatient setting in a large healthcare system in the US mid-Atlantic region. METHODS: Data was abstracted from the EHR on all outpatients from 1/1/2017 through 10/31/2021, including individual demographics and their HCV antibody (Ab) screening dates. For a limited period centered on the implementation of the HCV alert, mixed effects multivariable regression analyses were performed to compare the timeline and characteristics of those screened and un-screened. The final models included socio-demographic covariates of interest, time period (pre/post) and an interaction term between time period and sex. We also examined a model with time as a monthly variable to look at the potential impact of COVID-19 on screening for HCV. RESULTS: Absolute number of screens and screening rate increased by 103% and 62%, respectively, after adopting the universal EHR alert. Patients with Medicaid were more likely to be screened than private insurance (ORadj 1.10, 95% CI: 1.05, 1.15), while those with Medicare were less likely (ORadj 0.62, 95% CI: 0.62, 0.65); and Black (ORadj 1.59, 95% CI: 1.53, 1.64) race more than White. CONCLUSIONS: Implementation of universal EHR alerts could prove to be a critical next step in HCV elimination. Those with Medicare and Medicaid insurance were not screened proportionately to the national prevalence of HCV in these populations. Our findings support increased screening and re-testing efforts for those at high risk of HCV.

Long-term Follow-up of Hepatitis C Patients Who Achieved Sustained Virologic Response in the Pragmatic PRIORITIZE Study.

Multiple real-world studies have confirmed the safety and efficacy of hepatitis C (HCV) direct-acting antivirals (DAAs); however, few studies have provided data on long-term outcomes of patients without cirrhosis after achieving sustained virologic response (SVR).1-3 The aims of this analysis were to describe, among individuals in the PRIORITIZE Study achieving SVR: (1) the frequency of laboratory testing and imaging during long-term follow-up (LTFU), (2) changes in liver tests, (3) occurrence of hepatic decompensation or hepatocellular carcinoma (HCC) and deaths, and (4) durability of SVR.

Oral Prescription Opioids as a High-Risk Indicator for Hepatitis C Infection: Another Step Toward HCV Elimination.

BACKGROUND: The opioid epidemic across the U.S. poses an array of public health concerns, especially HCV transmission. HCV is now widely curable, yet incident rates are increasing due to the opioid epidemic. Despite the established trajectory from oral prescription opioids (OPOs) to opioid use disorder (OUD), OUD to injection drug use (IDU), and IDU to hepatitis C virus (HCV), OPOs are not a defined risk factor (RF) for HCV infection. The objective of this study was to observe rates of HCV testing and Ab reactivity (HCVAb+) in patients receiving OPOs to substantiate them as a RF, ultimately contributing to HCV elimination. METHODS: Data from MedStar Health patients receiving OPOs from 1/2017 to 12/2018 were collected and analyzed using chi-squared or student t-tests and logistic regression for uni- or multi-variable analyses, respectively. Statistical significance was defined as P < .05; Epi Info and SAS v 9·4 were used for statistical analyses; IRB approval was received. RESULTS: There were 115 415 individuals prescribed OPOs over the study period. In this population, 8.6% (932) were HCVAb+ when tested and not previously diagnosed (10 900); 3.4% (3893) had an OUD diagnosis, 20.6% (803) of whom were HCV tested; 25.4% (361) of all HCVAb+ (1421) had an OUD diagnosis. OUD (ORadj 8.53 [7.22-10.07]) was an independent predictor of HCVAb+ in this population. CONCLUSIONS: (1) In a large population prescribed oral opioids, HCVAb+ was 8.6%, higher than our previously published data (2.5%) and the US rate (1.7%); (2) only 20% of patients diagnosed with OUD were tested; and (3) only 25% of HCVAb+ patients were classified with OUD; this suggests underreporting of OUD in this population. Primary Care and Community Health Recommendations: (1) Re-testing for HCV in patients taking OPOs; (2) increased HCV testing among OUD patients; and (3) improved surveillance and reporting of OUD.

A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.

BACKGROUND AND AIMS: Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable. APPROACH AND RESULTS: We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication nonadherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breastfeeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 US viral hepatitis clinics. Participants were randomized (± ribavirin) to LDV/SOF, elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD; treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication nonadherence. Between June 2016 and March 2018, 1,609 participants were randomized. Among 1,128 participants who received ≥1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 was 95.2% (95% CI, 92.8%-97.6%) and 97.4% (95% CI, 95.5%-99.2%), respectively, with a difference estimate of 2.2% (-0.5% to 4.7%), falling within the "equivalence" interval (-5% to 5%). While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication nonadherence were similar. Study limitations were dropout due to insurance denial and loss to follow-up after treatment, limiting the ability to measure SVR12. CONCLUSIONS: This pragmatic trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR and LDV/SOF.

HIV testing in patients who are HCV positive: Compliance with CDC guidelines in a large healthcare system.

BACKGROUND: There are approximately 300,000 people in the United States who are co-infected with HIV and HCV. Several organizations recommend that individuals who are HCV infected, as well as persons over the age of 13, should be HIV tested. Comorbidities associated with HCV can be reduced with early identification of HIV. Our objective was to determine whether providers routinely followed HIV testing guidelines for patients who tested HCV positive (HCV+). METHODS: A retrospective chart review was conducted of all patients in primary care at an academic health system from 7/2015-3/2017 who tested HCV+. As part of a primary database, HCV testing data was collected; HIV testing data was abstracted manually. We collected and described the intervals between HCV and HIV tests. To determine associations with HIV testing univariable and multivariable analyses were performed. RESULTS: We identified 445 patients who tested HCV+: 56.6% were tested for HIV, the mean age was 57 ± 10.9 years, 77% were from the Birth Cohort born 1945-1965 (BC); 61% were male; and 51% were Black/AA. Patients in the BC were more likely to be HIV tested if they were: male (p = 0.019), Black/AA (p<0.001), and had Medicaid (p = 0.005). These differences were not found in the non-BC. Six patients who were tested for both HIV and HCV were found to be newly HIV positive at the time of testing. CONCLUSION: As demonstrated, providers did not routinely follow CDC recommendations as almost half of the HCV+ patients were not correctly tested for HIV. It is important to emphasize that six persons were tested HIV positive simultaneously with their HCV+ diagnosis. If providers did not follow the CDC guidelines, then these patients may not have been identified. Improvements in EHR clinical decision support tools and provider education can help improve the HIV testing rate among individuals who are HCV+.

Characteristics and Outcomes of COVID-19 Infection from an Urban Ambulatory COVID-19 Clinic-Guidance for Outpatient Clinicians in Triaging Patients.

BACKGROUND: Coronavirus infection (COVID) presents with flu-like symptoms and can cause serious complications. Here, we discuss the presentation and outcomes of COVID in an ambulatory setting along with distribution of positive cases amongst healthcare workers (HCWs). METHOD: Patients who visited the COVID clinic between 03/11/2020 and 06/14/2020 were tested based on the CDC guidelines at the time using PCR-detection methods. Medical records were reviewed and captured on a RedCap database. Statistical analysis was performed using both univariate and bivariate analysis using Fischer's exact test with 2-sided P values. RESULTS: Of the 2471 evaluated patients, 846 (34.2%) tested positive for COVID. Mean age of positivity was 43.4 years (SD ± 15.4), 60.1% were female and 49% were Black. 58.7% of people tested had a known exposure, and amongst those with exposure, 57.3% tested positive. Ninety-four patients were hospitalized (11.1%), of which 22 patients (23.4%) required ICU admission and 10 patients died. The overall death rate of patients presenting to clinic was 0.4%, or 1.2% amongst positive patients. Median length of hospital stay was 6 days (range 1-51). Symptoms significantly associated with COVID included: anosmia, fever, change in taste, anorexia, myalgias, cough, chills, and fatigue. Increased risk of COVID occurred with diabetes, whereas individuals with lung disease or malignancy were not associated with increased risk of COVID. Amongst COVID positive HCWs, the majority were registered nurses (23.4%), most working in general medicine (39.8%) followed by critical care units (14.3%). DISCUSSION/CONCLUSION: Blacks and females had the highest infection rates. There was a broad range in presentation from those who are very ill and require hospitalization and those who remain ambulatory. The above data could assist health care professionals perform a targeted review of systems and co-morbidities, allowing for appropriate patient triage.

Clearance of Hepatitis C Virus (HCV) Is Associated With Improved Outcomes in HCV-Associated Lymphoma.

BACKGROUND: Improved hepatitis C virus (HCV) clearance due to directly acting antiviral agents has led to remarkably improved outcomes of indolent HCV-associated non-Hodgkin lymphoma (NHL). The impact of directly acting antivirals on the outcomes of aggressive NHL is still under investigation. Characteristics of HCV-associated NHL in black patients are not well characterized. We report outcomes of HCV-associated NHL compared to their HCV-negative counterparts in a predominantly black population. PATIENTS AND METHODS: Patients with lymphoma between January 2007 and December 2017 were retrospectively studied. Depending on presence or absence of HCV RNA, patients were grouped into HCV positive (HCV+) and HCV negative (HCV-) cohorts. Depending on virologic clearance (VC), HCV+ were classified into HCV+ with VC and HCV+ without VC. Overall response rate (ORR), complete response, overall survival (OS), and progression-free survival (PFS) of HCV+ patients with and without VC were compared to HCV- patients. RESULTS: Of 397 patients with lymphoma, 40 had HCV. Black comprised 90% of HCV+ patients. Diffuse large B-cell lymphoma was most frequent (47%) in the HCV+ group. HCV+ patients without VC had significantly worse OS and PFS compared to HCV- patients. There were no differences in ORR, complete response, PFS, and OS of HCV+ patients with VC and HCV- patients. These results were consistent in subgroups of diffuse large B-cell lymphoma and aggressive lymphoma. CONCLUSION: HCV clearance is positively associated with lymphoma outcomes in black patients. Patients who clear HCV have noninferior outcomes to HCV- patients, while those who fail to clear HCV have significantly worse outcomes.

Identification of Risk Factors for Testing of Hepatitis C in Non-Birth Cohort Patients: Is Universal Screening Necessary?

OBJECTIVES: CDC reported that 45% of Hepatitis C (HCV) infected people denied known risk factors. Electronic health record RF-based, non-Birth Cohort (born outside of years 1945-1965) screening is challenging as risk factors are often input as nonsearchable data. Testing non-Birth Cohort patients solely based on risk factors has the potential to miss a substantial number of HCV infected patients. The aim was to determine the HCV antibody positive prevalence who would have been missed had providers only followed risk factor based screening recommendations. METHODS: A 1:3 case-control retrospective nested chart review was conducted. HCV risk factors and opioid prescriptions were manually abstracted from the Electronic Health Record; other variables were collected using Explorys. In July 2015 HCV screening data was collected on non-Birth Cohort patients who were HCV tested across MedStar Health, as a presumptive marker for high risk. Univariate and multivariate logistic regression models were utilized to determine HCV antibody positive predictors. RESULTS: Eighteen (23%) HCV antibody positive and 123 (49%) HCV antibody negative had no identified risk factors; 6 (33%) HCV antibody positive reported risk factors only after a positive test result. There was a significant interaction between age over 40 and opioid prescription use; these groups were 11× more likely to be HCV antibody positive (CI95 1.6-74.8). CONCLUSIONS: HCV testing solely based on presence of risk factors in non-Birth Cohort patients has the potential to miss a significant number of HCV antibody positive patients. Given patient- and provider-level barriers in elucidating risk factors, universal HCV antibody screening may be warranted.

Leveraging the electronic health record to eliminate hepatitis C: Screening in a large integrated healthcare system.

Highly efficacious and tolerable treatments that cure hepatitis C viral (HCV) infection exist today, increasing the feasibility of disease elimination. However, large healthcare systems may not be fully prepared for supporting recommended actions due to knowledge gaps, inadequate infrastructure and uninformed policy direction. Additionally, the HCV cascade of care is complex, with many embedded barriers, and a significant number of patients do not progress through the cascade and are thus not cured. The aim of this retrospective cohort study was to evaluate a large healthcare system's HCV screening rates, linkage to care efficiency, and provider testing preferences. Patients born during 1945-1965, not previously HCV positive or tested from within the Electronic Health Record (EHR), were identified given that three-quarters of HCV-infected persons in the United States are from this Birth Cohort (BC). In building this HCV testing EHR prompt, non-Birth Cohort patients were excluded as HCV-specific risk factors identifying this population were not usually captured in searchable, structured data fields. Once completed, the BC prompt was released to primary care locations. From July 2015 through December 2016, 11.5% of eligible patients (n = 9,304/80,556) were HCV antibody tested (anti-HCV), 3.8% (353/9,304) anti-HCV positive, 98.1% (n = 311/317) HCV RNA tested, 59.8% (n = 186/311) HCV RNA positive, 86.6% (161/186) referred and 76.4% (n = 123/161) seen by a specialist, and 34.1% (n = 42/123) cured of their HCV. Results from the middle stages of the cascade in this large healthcare system are encouraging; however, entry into the cascade-HCV testing-was performed for only 11% of the birth cohort, and the endpoint-HCV cure-accounted for only 22% of all infected. Action is needed to align current practice with recommendations for HCV testing and treatment given that these are significant barriers toward elimination.

Use of direct-acting antivirals for hepatitis C viral infection and association with intrahepatic cholangiocarcinoma: Is there a linkage?

Hepatitis C viral infection is recognized worldwide as a leading cause of cirrhosis and hepatocellular carcinoma. The goal of hepatitis C viral antiviral therapy is the permanent eradication of hepatitis C viral RNA, commonly referred to as a sustained virologic response - defined as "undetectable" RNA at 12 weeks following the completion of therapy. Hepatitis C viral treatment has dramatically advanced with the FDA approval of several new agents known as direct-acting antivirals. These drugs target specific nonstructural proteins of the virus, which disrupt viral replication, and therefore halt infection. However, recently, there has been a concern for increased risk of recurrence of treated hepatocellular carcinoma or denovo occurrence of hepatocellular carcinoma after treatment with direct-acting antivirals. We are now reporting three cases of intrahepatic cholangiocarcinoma that developed after sustained virologic response following hepatitis C viral treatment with direct-acting antivirals.

High Hepatitis C Infection Rate Among Baby Boomers in an Urban Primary Care Clinic: Results from the HepTLC Initiative.

OBJECTIVE: CDC recommends that all people born between 1945 and 1965 be tested for hepatitis C virus (HCV). We hypothesized that HCV testing in a large, urban primary care clinic would reveal higher rates of HCV infection than previously published. METHODS: Through the Hepatitis Testing and Linkage to Care initiative, the primary care clinic at MedStar Washington Hospital Center in Washington, DC, provided HCV antibody (anti-HCV) testing and linkage to care from October 2012 through September 2013 for patients born between 1945 and 1965 without previously noted risk factors. We collected data on age, race/ethnicity, sex, anti-HCV and HCV ribonucleic acid (RNA) results, risk factors in those who tested anti-HCV positive, and health insurance type and made comparisons using c(2) and Student's t-tests. RESULTS: Of 1,123 patients tested, the mean age was 57 years, 742 (66.1%) were women, 969 (86.3%) were black/African American, and 654 (58.2%) had public health insurance. Of the 99 (8.8%) patients who tested anti-HCV positive, the mean age was 58 years, 54 were men, and 93 were black/African American; 41 of 74 anti-HCV-positive patients were intravenous drug users. Of 82 anti-HCV-positive patients, 51 were HCV RNA positive. Of the black/African American patients tested, 49 of 317 men (15.5%) and 44 of 652 women (6.7%) were anti-HCV positive (p,0.001). The HCV prevalence rate in the birth cohort (8.8%) was significantly higher than the U.S. (3.3%) and DC (2.5%) rates (p,0.001), and the HCV prevalence rate among black/African American men in DC (15.5%) was substantially higher than the prevalence rate reported by CDC (8.1%). CONCLUSION: Testing initiatives in primary care settings need to be more rigorously upheld, and internal champions are needed to advocate for increased screening to ensure linkage to care and engagement in the HCV care cascade.

Case series of Bartonella quintana blood culture-negative endocarditis in Washington, DC.

INTRODUCTION: Prior studies (predominantly from Europe) have demonstrated blood culture-negative endocarditis due to Bartonella. Our objective was to describe three cases of Bartonella quintana endocarditis identified within one year at a large hospital in Washington, DC, USA. CASE PRESENTATION: We constructed a descriptive case series from a retrospective review of medical records from April to December 2013 at an 800-bed urban hospital. All three patients (ages: 52, 55 and 57 years) were undomiciled/homeless men with a history of alcoholism. Although they had negative blood cultures, echocardiography demonstrated aortic/mitral valve perforation and regurgitation in one patient, aortic/mitral valve vegetation with mitral regurgitation in the second patient, and aortic valve vegetation with regurgitation in the third patient. The patients had positive Bartonella quintana serum immunoglobulin G (IgG) with negative immunoglobulin M (IgM). PCR on DNA extracted from cardiac valves was positive for Bartonella, and DNA sequencing of PCR amplicons identified Bartonella quintana. Patients received treatment with doxycycline/rifampin or doxycycline/gentamicin. CONCLUSION: Clinicians should consider Bartonella endocarditis as a differential diagnosis in patients who fit elements of the Duke Criteria, as well as having a history of homelessness and alcoholism.

Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1.

BACKGROUND: The combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1). METHODS: This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1. Previously untreated patients were randomly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a standard dose of 60 mg daily (with dose adjustment for concomitant antiretroviral medications) plus 400 mg of sofosbuvir daily. Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses. The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks. RESULTS: Patients had HCV genotypes 1 through 4 (83% with genotype 1), and 14% had compensated cirrhosis; 98% were receiving antiretroviral therapy. Among patients with genotype 1, a sustained virologic response was reported in 96.4% (95% confidence interval [CI], 89.8 to 99.2) who were treated for 12 weeks and in 75.6% (95% CI, 59.7 to 87.6) who were treated for 8 weeks among previously untreated patients and in 97.7% (95% CI, 88.0 to 99.9) who were treated for 12 weeks among previously treated patients. Rates of sustained virologic response across all genotypes were 97.0% (95% CI, 91.6 to 99.4), 76.0% (95% CI, 61.8 to 86.9), and 98.1% (95% CI, 89.7 to 100), respectively. The most common adverse events were fatigue, nausea, and headache. There were no study-drug discontinuations because of adverse events. HIV-1 suppression was not compromised. CONCLUSIONS: Among previously untreated HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir for HCV infection, the rate of sustained virologic response across all genotypes was 97.0% after 12 weeks of treatment and 76.0% after 8 weeks. (Funded by Bristol-Myers Squibb; ALLY-2 ClinicalTrials.gov number, NCT02032888.).

Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial.

IMPORTANCE: The efficacy of directly acting antiviral agents in interferon-free regimens for the treatment of chronic hepatitis C infections needs to be evaluated in different populations. OBJECTIVE: To determine the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin among a population with unfavorable treatment characteristics. DESIGN, SETTING, AND PATIENTS: Single-center, randomized, 2-part, open-label phase 2 study involving 60 treatment-naive patients with hepatitis C virus (HCV) genotype 1 enrolled at the National Institutes of Health (October 2011-April 2012). INTERVENTIONS: In the study's first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks. In the second part, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion (sustained virologic response of 24 weeks [SVR24]). RESULTS: In the first part of the study, 9 participants (90%; 95% CI, 55%-100%) achieved SVR24. In the second part, 7 participants (28%) in the weight-based group and 10 (40%) in the low-dose group relapsed after treatment completion leading to SVR24 rates of 68% (95% CI, 46%-85%) in the weight-based group and 48% (95% CI, 28%-69%; P = .20) in the low-dose group. Twenty individuals participated in a pharmacokinetic-viral kinetic substudy, which demonstrated a slower loss rate of infectious virus in relapsers than in participants who achieved SVR (clearance, 3.57/d vs 5.60/d; P = .009). The most frequent adverse events were headache, anemia, fatigue, and nausea. There were 7 grade 3 events including anemia, neutropenia, nausea, hypophosphatemia, and cholelithiasis or pancreatitis. No one discontinued treatment due to adverse events. CONCLUSION AND RELEVANCE: In a population of patients with a high prevalence of unfavorable traditional predictors of treatment response, a 24-week regimen of sofosbuvir and weight-based or low-dose ribavirin resulted in SVR24 rates of 68% and 48%, respectively. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01441180.

Effects of Angiotensin Converting Enzyme Inhibitors on Liver Fibrosis in HIV and Hepatitis C Coinfection.

Background. Liver fibrosis is accelerated in HIV and hepatitis C coinfection, mediated by profibrotic effects of angiotensin. The objective of this study was to determine if angiotensin converting enzyme inhibitors (ACE-Is) attenuate liver fibrosis in coinfection. Methods. A retrospective review of 156 coinfected subjects was conducted to analyze the association between exposure to ACE-Is and liver fibrosis. Noninvasive indices of liver fibrosis (APRI, FIB-4, Forns indices) were compared between subjects who had taken ACE-Is and controls who had not taken them. Linear regression was used to evaluate ACE-I use as an independent predictor of fibrosis. Results. Subjects taking ACE-Is for three years were no different than controls on the APRI and the FIB-4 but had significantly higher scores than controls on the Forns index, indicating more advanced fibrosis. The use of ACE-Is for three years remained independently associated with an elevated Forns score when adjusted for age, race, and HIV viral load (P < 0.001). There were significant associations between all of the indices and significant fibrosis, as determined clinically and radiologically. Conclusions. There was not a protective association between angiotensin inhibition and liver fibrosis in coinfection. These noninvasive indices may be useful for ruling out significant fibrosis in coinfection.

ITPA gene polymorphisms significantly affect hemoglobin decline and treatment outcomes in patients coinfected with HIV and HCV.

Published studies have described a strong association with a single-nucleotide polymorphism (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene and ribavirin (RBV)-induced hemolytic anemia in HCV-infected patients receiving pegylated interferon (pegIFN) and RBV. This study sought to evaluate the effect of these polymorphisms on anemia, hemoglobin reduction, HCV kinetics, and treatment outcomes. Sixty-three patients coinfected with HIV and HCV and 58 patients infected with HCV only were treated with pegIFN/RBV were genotyped using the ABI TaqMan allelic discrimination kit for the 2 ITPA SNP variants rs1127354 and rs7270101. A composite variable of ITPA deficiency using both SNPs was created as previously reported. Statistical analysis was performed using Mann-Whitney test or Chi square/Fishers exact test for categorical data and mixed model analysis for multiple variables. Thirty-five patients (30%) were predicted to have reduced ITPA activity. ITPA deficiency was found to be protective against the development of hemoglobin reduction >3 g/dl over the course of treatment. The rates of hemoglobin reduction >3 g/dl decreased in correlation with the severity of ITPA deficiency. ITPA deficiency was associated with slower hemoglobin decline early in treatment (week 4, P = 0.020) and rapid virologic response (RVR) at week 4 (P = 0.017) in patients coinfected with HIV and HCV. ITPA polymorphisms are associated with hemoglobin decline and in patients coinfected with HIV and HCV it is also associated with early virologic outcomes. Determination of ITPA polymorphisms may allow prediction of RBV-induced anemia and earlier initiation of supportive care to ensure optimal therapeutic outcomes.

Low rates of hepatitis A and B vaccination in patients with chronic hepatitis C at an urban methadone maintenance program.

Patients with chronic hepatitis C virus (HCV) are at increased risk for complications of liver disease if they become infected with the hepatitis A (HAV) or hepatitis B (HBV) viruses. The authors examined the rates of testing for HAV, HBV, and HCV, as well as rates of vaccination against HAV and HBV in patients with chronic HCV in a random sample (N = 207) of medical records of patients enrolled in a methadone maintenance program. Almost all patients reviewed were tested for HAV, HBV, and HCV. Of the 111 patients with chronic HCV, 53 (48.6%) and 68 (63%) lacked immunity to HAV and HBV, respectively. Of those lacking immunity, 29 (54.7%) and 2 (2.9%) were vaccinated for HAV and HBV, respectively. Despite high rates of testing for HAV, HBV, and HCV at a methadone maintenance program, approximately half of those with chronic HCV eligible for the HAV vaccine received it, and few of those eligible for HBV vaccine received it.

Prevalence and patient awareness of medical comorbidities in an urban AIDS clinic.

Mortality in HIV-positive persons is increasingly due to non-HIV-related medical comorbidities. There are limited data on the prevalence and patient awareness of these comorbid conditions. Two hundred subjects at an urban HIV clinic were interviewed in 2005 to assess their awareness of 15 non-HIV-related medical comorbidities, defined as medical problems that are neither AIDS-defining by standard definitions, nor a direct effect of immune deficiency. Medical charts were subsequently reviewed to establish prevalence and concordance between self-report and chart documentation. Eighty-four percent of subjects self-reported at least 1 of 15 medical comorbidities and 92% had at least 1 condition chart-documented. The top 5 chart-documented conditions were hepatitis C (51.5%), pulmonary disease (28.5%), high blood pressure (27%), high cholesterol (24.5%), and obesity (22.5%). In multivariate analysis, higher number of non-HIV-related medical comorbidities was associated with older age, female gender, and intravenous drug use as route of HIV transmission. Across self-reported non-HIV-related medical comorbidities, the absolute concordance rate ranged from 67% to 96%, the sensitivity ranged from 0% to 79%; the positive predictive value ranged from 0% to 100%. While the vast majority of largely urban minority HIV-positive subjects were diagnosed with non-HIV-related medical comorbidities, there is significant room for improvement in patient awareness. In order to help patients optimally access and adhere to medication and medical care for these non-HIV-related medical comorbidities, interventions and educational campaigns to improve patient awareness that take cultural background, literacy, and educational level into account should be developed, implemented, and evaluated.

HIV and Hepatitis B Virus Coinfection: Approach to Management: Case Study and Commentary.

OBJECTIVE: To review diagnosis and treatment in patients with HIV and hepatitis B virus (HBV) coinfection. METHODS: Review of the literature in the context of a clinical case. RESULTS: All patients with HIV should be screened for the presence of coinfection with HBV. Following diagnosis with HBV infection, the level of HBV activity should be assessed with testing for HBeAg, HBV DNA, and potentially a biopsy for staging the degree of fibrosis present. Based on the results of this workup, a decision regarding the role of anti-hepatitis treatment should be made. According to the latest chronic hepatitis B and HIV treatment guidelines, coinfected patients who require treatment for chronic hepatitis B should be started on a regimen that is fully active against both HIV and HBV. A first-line regimen for coinfected patients is generally composed of tenofovir and emtricitabine, plus one other agent active against HIV. In coinfected patients, durable responses are rare, and therefore patients are usually required to remain on therapy indefinitely. CONCLUSION: Intensification of surveillance techniques and education programs should be developed to help prevent transmission of infection and integrate coinfected patients into the health care system. Once engaged in care, coinfected patients should receive treatment for both HIV and chronic hepatitis B with the goal of a decrease in liver failure, cirrhosis, hepatocellular carcinoma, and chronic hepatitis B-related mortality.

Chronic kidney disease in HIV infection: an urban epidemic.

Kidney disease is an important complication of HIV, particularly in minority populations. We describe the burden of chronic kidney disease among 1239 adults followed at an urban AIDS center, with an estimated prevalence of 15.5% (n = 192). Independent predictors of kidney disease included older age, black race, hepatitis C virus exposure, and lower CD4 cell count. These data suggest that chronic kidney disease remains a common complication of HIV infection in the era of antiretroviral therapy.