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1.  ITPA Gene Polymorphisms Significantly Affect Hemoglobin Decline and Treatment Outcomes in Patients Coinfected With HIV and HCV 
Journal of medical virology  2012;84(7):1106-1114.
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 Taq-Man 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.
doi:10.1002/jmv.23302
PMCID: PMC3518921  PMID: 22585729
ribavirin-induced hemolytic anemia; ITPA; HIV/HCV; pharmacogenomics
2.  HIV and Hepatitis B Virus Coinfection: Approach to Management 
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.
PMCID: PMC3677863  PMID: 23761953
3.  Effects of Angiotensin Converting Enzyme Inhibitors on Liver Fibrosis in HIV and Hepatitis C Coinfection 
AIDS Research and Treatment  2012;2012:978790.
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.
doi:10.1155/2012/978790
PMCID: PMC3501811  PMID: 23193466
4.  Low rates of hepatitis A and B vaccination in patients with chronic hepatitis C at an urban methadone maintenance program 
Journal of addictive diseases  2010;29(4):461-465.
Aims
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. All major guidelines for the management of patients with chronic HCV include the recommendation for vaccination against HAV and HBV for those who are not already immune. We 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 infection at a methadone maintenance program (MMP).
Design, Participants, and Setting
Retrospective review of a random sample (n=207) of medical records of patients enrolled in an academically affiliated, urban MMP providing on-site primary care services.
Measurements
Serostatus for HAV, HBV, and HCV and rates of vaccination for HAV and HBV in those patients with chronic HCV.
Findings
Almost all patients reviewed were tested for HAV, HBV, and HCV. Of the 111 patients found to be chronically infected with HCV, 53 (48.6%) and 68 (63%) were found to lack immunity to HAV and HBV respectively. Of those lacking immunity, 29 (54.7%) and 2 (2.9%) were then vaccinated for HAV and HBV respectively.
Conclusions
Despite high rates of testing for HAV, HBV, and HCV at an urban methadone maintenance program, approximately half of those with chronic HCV eligible for the HAV vaccine received it and very few of those eligible for HBV vaccine received it.
doi:10.1080/10550887.2010.509281
PMCID: PMC2982770  PMID: 20924882
5.  Prevalence and Patient Awareness of Medical Comorbidities in an Urban AIDS Clinic 
AIDS Patient Care and STDs  2010;24(1):39-48.
Abstract
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.
doi:10.1089/apc.2009.0152
PMCID: PMC2859780  PMID: 20095901
6.  Hepatitis C Patients' Self-reported Adherence to Pegylated Interferon and Ribavirin 
Background
Prior research on adherence to Hepatitis C treatment has documented rates of dose reductions and early treatment discontinuation, but little is known about patients' dose-taking adherence.
Aims
To assess the prevalence of missed doses of pegylated interferon and ribavirin and examine the correlates of dose-taking adherence in clinic settings.
Methods
180 patients on treatment for Hepatitis C (23% co-infected with HIV) completed a cross-sectional survey at the site of their Hepatitis C care.
Results
Seven percent of patients reported missing at least one injection of pegylated interferon in the last four weeks and 21% reported missing at least one dose of ribavirin in the last 7 days. Dose-taking adherence was not associated with HCV viral load.
Conclusions
Self-reported dose nonadherence to Hepatitis C treatment occurs frequently. Further studies of dose nonadherence (assessed by method other than self-report) and its relationship to HCV virologic outcome are warranted.
PMCID: PMC2891196  PMID: 19086329
Adherence; HCV; HIV; co-infection; interferon; ribavirin

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