Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.-Canadian multicenter study.

BACKGROUND/AIMS: HIV-infected patients now live longer and often have complications of liver disease, especially with hepatitis B or C virus coinfection. Limited data are available on those with hepatocellular carcinoma (HCC). METHODS: A retrospective analysis from 1992 to 2005 in 6 centers identified 63 HIV-infected HCC patients. Controls were 226 consecutive HIV-negative HCC patients from four sites. RESULTS: HIV-positive patients were younger than controls (52 vs. 64 years, p<0.001), more commonly had chronic hepatitis B or C (97% vs. 73%, p<0.001), were more frequently symptomatic (51% vs. 38%, p=0.048), had a higher median alfa-fetoprotein level (227 vs. 51 ng/ml, p=0.005), but a similar mean Child-Turcotte-Pugh score (7.0 vs. 7.5, p=0.05) and HCC staging score (Barcelona-Clínic-Liver-Cancer stages C+D in 50% vs. 58%, p=0.24). HCC developed faster in HIV/HCV-coinfected than in HCV-monoinfected patients (mean, 26 vs. 34 years after HCV infection, p=0.002). HIV-positive patients received proven therapy more often (48% vs. 31%, p=0.017), but median survival was similar (6.9 vs. 7.5 months, p=0.44). Independent factors predicting survival were symptomatic presentation (hazard ratio [HR], 0.437; p<0.001), any proven therapy (HR, 2.19; p<0.001), diagnosis after 01-Jan-2002 (HR, 1.52; p=0.010), Barcelona-Clínic-Liver-Cancer stages C+D (HR, 0.491; p<0.001), AST/ALT >or= 2.00 (HR, 0.597; p=0.001), AFP >or= 400 ng/mL (HR, 0.55, p=0.003), and platelets >or= 100,000/mm3 (HR, 0.651; p=0.012), but not HIV-serostatus (p=0.19). In HIV-infected patients without HCC therapy (n=33), median survival was longer with undetectable HIV RNA (<400 copies/mL) than with HIV viremia (6.5 vs. 2.6 months, p=0.013). CONCLUSIONS: HIV-positive HCC patients are younger and more frequently symptomatic and infected with HCV or HBV than HIV-negative patients. Tumor staging and survival are similar. In untreated patients, undetectable HIV RNA independently predicts better survival.

Rate and predictors of treatment prescription for hepatitis C.

BACKGROUND: The true treatment rate for hepatitis C virus (HCV) in veterans is unknown. AIM: To determine the treatment prescription rates and predictors of treatment prescription for HCV in a large national population. METHODS: The Department of Veterans Affairs National Patient Care Database (NPCD) was used to identify all HCV-infected people between the fiscal years 1999 and 2003 using the International classification of diseases, 9th revision codes. Demographic information, medical and psychiatric comorbidities, and drug and alcohol use diagnoses were retrieved. Pharmacy data were retrieved from the Department of Veterans Affairs Pharmacy Benefits Management (PBM) database. Logistic regression analysis was used to determine the predictors of treatment for HCV in HCV. RESULTS: 113 927 veterans in the Department of Veterans Affairs care with a diagnosis of HCV were identified. The treatment prescription rate for HCV was 11.8%. Patients not prescribed treatment were older, more likely to be from minority races, have more alcohol and drug misuse, and have medical and psychiatric comorbid conditions. In a multivariate logistic regression model, the following factors were predictive of non-treatment for HCV: increasing age (odds ratio (OR) 0.77 for each 5-year increase in age; 95% confidence interval (CI) 0.76 to 0.78); black race (OR 0.64; 95% CI 0.6 to 0.68); Hispanic race (OR 0.88; 95% CI 0.8 to 0.96); alcohol abuse and dependence (OR 0.62; 95% CI 0.59 to 0.65); drug abuse and dependence (OR 0.78; 95% CI 0.74 to 0.82); anaemia (OR 0.18; 95% CI 0.16 to 0.21); hepatitis B infection (OR 0.72; 95% CI 0.62 to 0.83); coronary artery disease (OR 0.9; 95% CI 0.85 to 0.97); stroke (OR 0.75; 95% CI 0.67 to 0.85); bipolar disorder (OR 0.64; 95% CI 0.58 to 0.70); major depression (OR 0.72; 95% CI 0.67 to 0.77); mild depression (OR 0.56; 95% CI 0.53 to 0.59); and schizophrenia (OR 0.71; 95% CI 0.65 to 0.77). The following factors were associated with a higher likelihood of treatment prescription for HCV: liver cirrhosis (OR 1.6; 95% CI 1.5 to 1.7); and diabetes (OR 1.07; 95% CI 1.02 to 1.12). CONCLUSIONS: A small number of HCV-infected veterans were prescribed treatment for HCV. Non-treatment is associated with increasing age, non-white race, drug and alcohol abuse, and dependence and comorbid illnesses. Reasons for non-treatment need further study.

Utilization and access to antiretroviral genotypic resistance testing and results within the US Department of Veterans Affairs.

OBJECTIVE: We sought to characterize variation in the use of HIV genotypic resistance tests and how results were reported. METHODS: Clinicians and laboratory managers at all Veterans Affairs (VA) medical centers were asked to complete a survey in March 2003 regarding HIV resistance testing practices. RESULTS: Surveys from 131 of 150 sites were returned. Forty-eight percent of HIV clinicians indicated that US Department of Health and Human Services guidelines were the usual basis for ordering tests. Although between 12% and 31% of respondents indicated that they always, sometimes, seldom, or never ordered resistance tests in patients with acute or chronic HIV infection, >70% ordered tests in adherent patients with treatment failure. Among the 32 centers with >200 patients in care, 13 +/- 8 (mean +/- standard deviation) tests were performed per 100 patients in care during 2002. Forty-nine percent of clinicians said that tests were helpful, but only 33% expressed confidence in using test results. Only 40% of sites entered results in the VA electronic medical record. CONCLUSION: Ordering patterns for HIV resistance tests differed significantly among VA sites. A minority of clinicians indicated confidence in the use of test results. A consistent system to capture and present complete results was absent.

Effects of hepatitis C virus coinfection on survival in veterans with HIV treated with highly active antiretroviral therapy.

BACKGROUND: With highly active antiretroviral therapy (HAART) available for patients with HIV, hepatitis C virus (HCV) infection has emerged as a potentially important cause of mortality in coinfected patients. Several studies have investigated the effect of coinfection on mortality, with conflicting results. METHODS: The study cohort consisted of HIV-infected veterans on HAART receiving care at US Department of Veterans Affairs facilities. Inclusion was based on first HAART prescription between January 1997 and February 2003, HCV antibody test result, and baseline CD4 and HIV viral load results within 1 year of starting HAART. We fitted Cox proportional hazards models to study the effect of HCV serostatus on survival time from HAART initiation, controlling for patient demographic and clinical characteristics, facility characteristics, HAART exposure, HAART response, and HCV treatment. RESULTS: Of 12,216 patients in the study cohort, 38% were HCV-seropositive. During an observation time averaging 3.5 years, 2087 patients died. The adjusted hazard ratio for HCV-seropositive patients was 1.56 (95% confidence interval [CI]: 1.42-1.70; P<0.0001) without a HAART exposure measure and 1.38 (95% CI: 1.26-1.51; P<0.0001) with the measure. We obtained similar results in analyses also controlling for HAART response. CONCLUSIONS: HCV seropositivity was independently associated with increased risk of death in a large cohort of HAART-treated HIV-infected veterans. Given the success of HAART in extending the lives of HIV patients, HCV has become an important predictor of their mortality.

Testing for hepatitis C virus infection should be routine for persons at increased risk for infection.

In the United States, chronic hepatitis C virus (HCV) infection affects an estimated 3 million persons, most younger than 50 years of age. It is one of the leading causes of chronic liver disease morbidity and mortality and the most common indication for liver transplantation. Effective treatment can eradicate the virus and eliminate or reduce liver inflammation and fibrosis, and counseling and immunization can modify or prevent the adverse effect of cofactors (for example, alcohol consumption or co-infections) on disease progression. However, controversy surrounds the need to routinely identify asymptomatic HCV-infected persons. Because no data currently demonstrate that treatment or other interventions will reduce future cases of HCV-related chronic disease and deaths, the U.S. Preventive Services Task Force found insufficient evidence to recommend for or against routine screening for HCV infection in adults at high risk. Chronic hepatitis C would require many years of follow-up to determine the incidence of complication after treatment of or other interventions in asymptomatic persons. It seems inappropriate to wait several decades to measure the impact of early identification of this viral infection when current data support a positive therapeutic effect that points to long-term benefits. In addition, treatment and other interventions must be provided before cirrhosis or liver failure occurs. Therefore, medical and public health professionals should continue the practice of screening persons for risk factors; offering testing to those at increased risk for HCV infection; and providing infected persons with appropriate counseling, medical evaluation, and treatment.

Electronic monitoring and counseling to improve medication adherence.

Electronic caps, pill caps that record the date and time of pill bottle opening provide an objective measure of adherence to prescribed medication. A promising intervention to improve adherence, cue-dose training, involves reviewing patients' pill cap-generated reports concerning their medication-taking and offering individualized recommendations for remembering to take medications at specific times of day. In this preliminary study, 79 patients prescribed the antihyperglycemic medication metformin had adherence assessed during a 4-week baseline period. Adherence, defined as proportion of prescribed doses taken within a predetermined 4-h window, was measured using electronic MEMS caps. Those who had less than 80% baseline adherence (n = 33) were randomly assigned to either receive 4 months of cue-dose training (n = 16) or to a control group (n = 17). Cue-dose training was associated with significantly better adherence to metformin (mean improvement of 15%). The effects of cue-dose training on adherence to other antihyperglycemic medication did not reach statistical significance. Glycosylated hemoglobin (a measure of blood sugar control) did not differ between groups. Data from nine patients who reviewed pill cap-generated data with their primary care providers suggested that both patients and providers found the discussion moderately helpful and not at all uncomfortable.

Effects of illicit drug use on adherence to prescribed antiretroviral medication.

This exploratory analysis compared adherence to antiretroviral medication on days that illicit drugs were used and on matched abstinence days in twelve subjects who used MEMS caps during participation in a clinical trial. Adherence on drug use days was lower in seven subjects, higher in one, and the same in four. Three subjects maintained 100% adherence despite illicit substance use on studied days. Thus, in a subset of patients, the actions involved in procuring drugs and the acute effects of using them contribute to non-adherence on those specific drug use days, associated with substance abuse. (Am J Addict 2003;12:455-458)

Neuropsychological correlates of suboptimal adherence to metformin.

The goal of this study was to determine if neuropsychological function is associated with adherence to prescribed medication. Altogether, 79 patients with type II diabetes at a VA primary care clinic had adherence to the antihyperglycemic drug metformin measured with MEMS caps over a 4-week period. They completed several tests of neuropsychological function: Mini-Mental Status Exam (MMSE), Trails A and B, Stroop, Digit Span, Digit Symbol, and Grooved Pegboard. In separate multivariate analyses, Stroop word score and time to complete Trails B were independently associated with adherence, as was age. Secondary analyses of the relationship between neuropsychological variables and other adherence-related measures were conducted. Low scores on the MMSE and non-Caucasian ethnicity were associated with missed appointments. None of the neuropsychological variables were associated with glycosylated hemoglobin. These results suggest that cognitive abilities should be considered when counseling patients concerning their adherence.