Relationship between alcohol use categories and noninvasive markers of advanced hepatic fibrosis in HIV-infected, chronic hepatitis C virus-infected, and uninfected patients.

BACKGROUND: It is unclear if the risk of liver disease associated with different levels of alcohol consumption is higher for patients infected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV). We evaluated associations between alcohol use categories and advanced hepatic fibrosis, by HIV and chronic HCV status. METHODS: We performed a cross-sectional study among participants in the Veterans Aging Cohort Study who reported alcohol consumption at enrollment (701 HIV/HCV-coinfected; 1410 HIV-monoinfected; 296 HCV-monoinfected; 1158 HIV/HCV-uninfected). Alcohol use category was determined by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and alcohol-related diagnoses and was classified as nonhazardous drinking, hazardous/binge drinking, or alcohol-related diagnosis. Advanced hepatic fibrosis was defined by FIB-4 index >3.25. RESULTS: Within each HIV/HCV group, the prevalence of advanced hepatic fibrosis increased as alcohol use category increased. For each alcohol use category, advanced hepatic fibrosis was more common among HIV-infected than uninfected (nonhazardous: 6.7% vs 1.4%; hazardous/binge: 9.5% vs 3.0%; alcohol-related diagnosis: 19.0% vs 8.6%; P < .01) and chronic HCV-infected than uninfected (nonhazardous: 13.6% vs 2.5%; hazardous/binge: 18.2% vs 3.1%; alcohol-related diagnosis: 22.1% vs 6.5%; P < .01) participants. Strong associations with advanced hepatic fibrosis (adjusted odds ratio [95% confidence interval]) were observed among HIV/HCV-coinfected patients with nonhazardous drinking (14.2 [5.91-34.0]), hazardous/binge drinking (18.9 [7.98-44.8]), and alcohol-related diagnoses (25.2 [10.6-59.7]) compared with uninfected nonhazardous drinkers. CONCLUSIONS: Advanced hepatic fibrosis was present at low levels of alcohol consumption, increased with higher alcohol use categories, and was more prevalent among HIV-infected and chronic HCV-infected patients than uninfected individuals. All alcohol use categories were strongly associated with advanced hepatic fibrosis in HIV/HCV-coinfected patients.

If it quacks like a duck: reviewing health care providers' speech restrictions under the first prong of Central Hudson.

The First Amendment protects the speech of health care providers. This protection can limit states' abilities to protect patients from harmful therapies involving speech, such as sexual orientation change efforts. Because providers' speech is more similar to commercial speech than traditional political discourse, it is possible to create a First Amendment review analysis that better balances states' police powers with providers' First Amendment rights. Under a "single-prong" approach, the first prong of Central Hudson can be used to identify quackery, which is analogous to false or misleading commercial speech and would therefore be outside the protection of the First Amendment. Because health care must be tailored to individual patients, restrictions on speech that survive the first prong of Central Hudson would be subject to strict scrutiny in order to leave the therapeutic decision to the provider and her patient, and maintain consistency with current jurisprudence. This Comment examines litigation from California's attempted ban on sexual orientation change therapy to illustrate the conflicts created by the current approach to First Amendment review of health care provider speech. This Comment then demonstrates the benefit of the proposed single-prong approach, including how it simultaneously protects patients from harm while protecting health care providers' speech.

Drug toxicity, HIV progression, or comorbidity of aging: does tipranavir use increase the risk of intracranial hemorrhage?

The US Food and Drug Administration has issued a warning that tipranavir may be associated with increased risk of intracranial hemorrhage. We studied 2 large cohorts to estimate the background rate of intracranial hemorrhage and compared it with rates reported among persons who had been exposed to tipranavir.

Does Clinical Inertia Vary According to Provider Type?

Despite the well established risks of persistently elevated blood pressure, as well as the benefits of controlling such elevations, hypertension remains underdiagnosed and undertreated. These VA researchers compared the rates of antihypertensive medication intensification between resident physicians, midlevel practitioners, and attending physicians.

Adherence, virological and immunological outcomes for HIV-infected veterans starting combination antiretroviral therapies.

OBJECTIVES: We aimed to determine adherence, virological, and immunological outcomes one year after starting a first combination antiretroviral therapy (ART) regimen. DESIGN: Observational; synthesis of administrative, laboratory, and pharmacy data. Antiretroviral regimens were divided into efavirenz, nevirapine, boosted protease inhibitor (PI), and single PI categories. Propensity scores were used to control for confounding by treatment assignment. Adherence was estimated from pharmacy refill records. SETTING: Veterans Affairs Healthcare System, all sites. PARTICIPANTS: HIV-infected individuals starting combination ART with a low likelihood of previous antiretroviral exposure. INTERVENTIONS: None. OUTCOMES: The proportion of antiretroviral prescriptions filled as prescribed, a change in log HIV-RNA, the proportion with log HIV-RNA viral suppression, a change in CD4 cell count. RESULTS: A total of 6394 individuals unlikely to have previous antiretroviral exposure started combination ART between 1996 and 2004, and were eligible for analysis. Adherence overall was low (63% of prescriptions filled as prescribed), and adherence with efavirenz (67%) and nevirapine (65%) regimens was significantly greater than adherence with boosted PI (59%) or single PI (61%) regimens (P < 0.001). Efavirenz regimens were more likely to suppress HIV-RNA at one year (74%) compared with nevirapine (62%), boosted PI (63%), or single PI (53%) regimens (all P < 0.001), and this superiority was maintained when analyses were adjusted for baseline clinical characteristics and propensity for treatment assignment. Efavirenz also yielded more favorable immunological outcomes. CONCLUSION: HIV-infected individuals initiating their first combination ART using an efavirenz-based regimen had improved virological and immunological outcomes and greater adherence levels.

Aging and infectious diseases: do patterns of comorbidity vary by HIV status, age, and HIV severity?

Patterns of comorbidity among persons with human immunodeficiency virus (HIV) are not well described. We compared comorbidity among veterans with and without HIV infection. The sample consisted of 33,420 HIV-infected veterans and 66,840 HIV-uninfected veterans. We identified and clustered 11 comorbid conditions using validated International Classification of Diseases, 9th Revision, Clinical Modification codes. We defined multimorbidity as the presence of conditions in all clusters. Models restricted to HIV-infected veterans were adjusted for CD4 cell count and viral load. Comorbidity was common (prevalence, 60%-63%), and prevalence varied by HIV status. Differences remained when the veterans were stratified by age. In multivariable analyses, older HIV-infected veterans were more likely to have substance use disorder and multimorbidity. Renal, vascular, and pulmonary diseases were associated with CD4 cell count <200 cells/mm(3); hypertension was associated with CD4 cell count >200 cells/mm(3). Comorbidity is the rule, and multimorbidity is common among veterans with HIV infection. Patterns of comorbidity differ substantially by HIV status, age, and HIV severity. Primary care guidelines require adaptation for persons with HIV infection.

Hepatocellular carcinoma and non-Hodgkin's lymphoma: the roles of HIV, hepatitis C infection, and alcohol abuse.

PURPOSE: To explore the relationship of HIV, hepatitis C (HCV), and alcohol abuse/dependence to risk for hepatocellular carcinoma and non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Male veterans (n = 14,018) with a first HIV diagnosis in the Veterans Affairs Healthcare System from October 1997 to September 2004; and 28,036 age-, race-, sex-, and location-matched HIV-negative veterans were identified. We examined the incidence of hepatocellular carcinoma and NHL and presence of HCV and alcohol abuse/dependence using International Classification of Diseases, ninth revision (ICD-9-CM) codes. HIV-positive to HIV-negative incident rate ratios (IRRs) and 95% CIs for the occurrence of hepatocellular carcinoma and NHL were calculated using Poisson regression models. RESULTS: HIV-positive veterans were at greater risk for hepatocellular carcinoma than HIV-negative veterans (IRR = 1.68; 95% CI, 1.02 to 2.77). After adjusting for HCV infection and alcohol abuse/dependence, HIV status was not independently associated with hepatocellular cancer (IRR = 0.96; 95% CI, 0.56 to 1.63). HIV-positive veterans had 9.71 times (95% CI, 6.99 to 13.49) greater risk of NHL than HIV-negative veterans. After adjusting for HCV and alcohol abuse/dependence, the IRR for NHL comparing HIV-positive with HIV-negative veterans is similar (IRR = 10.03, 95% CI, 7.19 to 13.97). CONCLUSION: HIV-positive veterans have a higher relative incidence of hepatocellular carcinoma and NHL than HIV-negative veterans. For hepatocellular carcinoma, this association appears to be largely explained by the higher prevalence of HCV and alcohol abuse/dependence. Efforts to decrease hepatocellular carcinoma among persons with HIV should focus primarily on detecting and treating HCV and reducing heavy alcohol use.

Health-related quality of life in veterans and nonveterans with HIV/AIDS.

PURPOSE: To compare health-related quality of life (HRQoL) between patients receiving care in Veterans Administration (VA) settings (veterans) and non-VA settings (nonveterans), and to explore determinants of HRQoL and change in HRQoL over time in subjects living with HIV/AIDS. SUBJECTS: One hundred veterans and 350 nonveterans with HIV/AIDS from 2 VA and 2 university-based sites in 3 cities interviewed in 2002 to 2003 and again 12 to 18 months later. METHODS: We assessed health status (functional status and symptom bother), health ratings, and health values (time tradeoff [TTO] and standard gamble [SG] utilities). We also explored bivariate and multivariable associations of HRQoL measures with a number of demographic, clinical, spiritual/religious, and psychosocial characteristics. RESULTS: Compared with nonveterans, the veteran population was older (47.7 vs 42.0 years) and consisted of a higher proportion of males (97% vs 83%), of participants with a history of injection drug use (23% vs 15%), and of subjects with unstable housing situations (14% vs 6%; P<.05 for all comparisons). On scales ranging from 0 (worst) to 100 (best), veterans reported significantly poorer overall function (mean [SD]; 65.9 [17.2] vs 71.9 [16.8]); lower rating scale scores (67.6 [21.7] vs 73.5 [21.0]), lower TTO values (75.7 [37.4] vs 89.0 [23.2]), and lower SG values (75.0 [35.8] vs 83.2 [28.3]) than nonveterans (P<.05 for all comparisons); however, in multivariable models, veteran status was only a significant determinant of SG and TTO values at baseline. Among other determinants that were associated with multiple HRQoL outcomes in baseline and follow-up multivariable analyses were: symptom bother, overall function, religiosity/spirituality, depressive symptoms, and financial worries. CONCLUSIONS: Veterans reported significantly poorer HRQoL than nonveterans, but when controlling for other factors, veteran status was only a significant determinant of TTO and SG health values at baseline. Correlates of HRQoL such as symptom bother, spirituality/religiosity, and depressive symptoms could be fruitful potential targets for interventions to improve HRQoL in patients with HIV/AIDS.

Development and verification of a "virtual" cohort using the National VA Health Information System.

BACKGROUND: The VA's integrated electronic medical record makes it possible to create a "virtual" cohort of veterans with and without HIV infection to monitor trends in utilization, toxicity, and outcomes. OBJECTIVES: We sought to develop a virtual cohort of HIV-infected veterans by adapting an existing algorithm, verifying this algorithm against independent clinical data, and finally identifying demographically-similar HIV-uninfected comparators. RESEARCH DESIGN: Subjects were identified from VA administrative data in fiscal years 1998-2003 using a modified existing algorithm, then linked with Immunology Case Registry (ICR, the VA's HIV registry) and Pharmacy Benefits Management (centralized database of outpatient prescriptions) to verify accuracy of identification. The algorithm was modified to maximize positive predictive value (PPV) against ICR. Finally, 2 HIV-uninfected comparators were matched to each HIV-infected subject. RESULTS: Using a single HIV code, 30,564 subjects were identified (positive predictive value 69%). Modification to require >1 outpatient or 1 inpatient code improved the positive predictive value to 88%. The lack of confirmatory laboratory and pharmacy data for the majority of subjects with a single outpatient code also supported this change. Of subjects identified with the modified algorithm, 89% had confirmatory evidence. When the modified algorithm was applied to fiscal years 1997-2004, 33,420 HIV-infected subjects were identified. Two HIV-uninfected comparators were matched to each subject for an overall cohort sample of 100,260. CONCLUSIONS: In the HAART era, HIV-related codes are sufficient for identifying HIV-infected subjects from administrative data when patients with a single outpatient code are excluded. A large cohort of HIV-infected subjects and matched comparators can be identified from existing VA administrative datasets.

Veterans Aging Cohort Study (VACS): Overview and description.

BACKGROUND: The Veterans Aging Cohort Study (VACS) is a study of human immunodeficiency virus (HIV) infected and uninfected patients seen in infectious disease and general medical clinics. VACS includes the earlier 3 and 5 site studies (VACS 3 and VACS 5) as well as the ongoing 8 site study. OBJECTIVES: We sought to provide background and context for analyses based upon VACS data, including study design and rationale as well as its basic protocol and the baseline characteristics of the enrolled sample. RESEARCH DESIGN: We undertook a prospectively consented multisite observational study of veterans in care with and without HIV infection. MEASURES: Data were derived from patient and provider self report, telephone interviews, blood and DNA samples, focus groups, and full access to the national VA "paperless" electronic medical record system. RESULTS: More than 7200 veterans have been enrolled in at least one of the studies. The 8 site study (VACS) has enrolled 2979 HIV-infected and 3019 HIV-uninfected age-race-site matched comparators and has achieved stratified enrollment targets for race/ethnicity and age and 99% of its total target enrollment as of October 30, 2005. Participants in VACS are similar to other veterans receiving care within the VA. VACS participants are older and more predominantly black than those reported by the Centers for Disease Control. CONCLUSIONS: VACS has assembled a rich, in-depth, and representative sample of veterans in care with and without HIV infection to conduct longitudinal analyses of questions concerning the association between alcohol use and related comorbid and AIDS-defining conditions.

Medical disease and alcohol use among veterans with human immunodeficiency infection: A comparison of disease measurement strategies.

BACKGROUND: Many people with human immunodeficiency (HIV) infection drink alcohol. We asked whether level of exposure to alcohol is associated with medical disease in a linear or nonlinear manner, whether the association depends upon the proximity of alcohol use, and whether it varies by source used to measure disease (chart review vs. ICD-9 Diagnostic Codes). METHODS: The Veterans Aging 3 Site Cohort Study (VACS 3) enrolled 881 veterans, 86% of all HIV-positive patients seen, at 3 VA sites from June 23, 1999, to July 28, 2000. To maximize the sensitivity for alcohol exposure, alcohol use was measured combining data from patient self-report, chart review, and ICD-9 codes. We assigned the greatest exposure level reported from any source. Alcohol use within the past 12 months was considered current. Data on comorbid and AIDS-defining medical diseases were collected via chart review and ICD-9 diagnostic codes. The association of alcohol use (level and timing) and disease was modeled only for diseases demonstrating > or =10% prevalence. Linearity was compared with nonlinearity of association using nested multivariate models and the likelihood ratio test. All multivariate models were adjusted for age, CD4 cell count, viral load, intravenous drug use, exercise, and smoking. RESULTS: Of 881 subjects enrolled, 866 (98%) had sufficient data for multivariate analyses, and 876 (99%) had sufficient data for comparison of chart review with ICD-9 Diagnostic Codes. Of the 866, 42 (5%) were lifetime abstainers; 247 (29%) were past drinkers; and 577 (67%) were current users. Among the 824 reporting past or current alcohol use, 341 (41%) drank in moderation, 192 (23%) drank hazardously, and 291 (35%) carried a diagnosis of abuse or dependence. ICD-9 codes showed limited sensitivity, but overall agreement with chart review was good for 15 of 20 diseases (kappa > 0.4). The following diseases demonstrated a > or =10% prevalence with both measures (hepatitis C, hypertension, diabetes, obstructive lung disease, candidiasis, and bacterial pneumonia). All of these were associated with alcohol use (P < 0.05). Hepatitis C, hypertension, obstructive lung disease, candidiasis, and bacterial pneumonia demonstrated linear associations with level of alcohol use (P < 0.03). Past alcohol use increased the risk of hepatitis C and diabetes after adjustment for level of exposure (P < 0.01). With the exception of candidiasis, the associations between level and timing of alcohol use were similar when measured by ICD-9 codes or by chart review. CONCLUSIONS: Past and current use of alcohol is common among those with HIV infection. Estimates of disease risk associated with alcohol use based upon ICD-9 Diagnostic Codes appear similar to those based upon chart review. After adjustment for level of alcohol exposure, past use is associated with similar (or higher) prevalence of disease as among current drinkers. Finally, level of alcohol use is linearly associated with medical disease. We find no evidence of a "safe" level of consumption among those with HIV infection.

Relative prevalence of comorbidities and treatment contraindications in HIV-mono-infected and HIV/HCV-co-infected veterans.

OBJECTIVES: To determine the prevalence of hepatitis C virus (HCV) co-infection among HIV-infected veterans, assess the prevalence of comorbid conditions that may complicate or limit treatment options, and ascertain whether comorbid conditions were more common in co-infected veterans. DESIGN AND METHODS: We used the Veterans Administration electronic medical records system to identify all veterans receiving care for HIV during fiscal years 1997-2002. Demographic data and diagnostic codes for HIV, HCV, and comorbid conditions were extracted. The validity of using diagnostic codes was assessed by calculating the agreement between chart extraction and electronic data on a separate sample of veterans. Factor analysis was used to identify the structure underlying the intercorrelation between comorbid conditions. Logistic regression was used to compare the prevalence of comorbid conditions and factors between HIV/HCV-co-infected and HIV-mono-infected veterans, adjusting for age and race. RESULTS: We identified 25,116 HIV-infected veterans in care, of whom 4489 (18%) were HCV co-infected. A validity assessment revealed moderate agreement between chart extraction and electronic data for each of the comorbid conditions assessed. HIV/HCV-co-infected veterans were significantly more likely to have each of the comorbid conditions, and to have significantly more comorbid conditions. Factor analysis revealed three dimensions of comorbidity: mental disorders, medical disorders, and alcohol-related complications. Veterans with co-infection were significantly more likely to have mental disorders and alcohol-related complications. CONCLUSIONS: HIV/HCV-co-infected veterans had a higher prevalence of comorbid conditions that may complicate and limit treatment options for HIV and for HCV co-infection. Strategies to improve treatment options for co-infected patients with comorbidities must be developed.

Differences between infectious diseases-certified physicians and general medicine-certified physicians in the level of comfort with providing primary care to patients.

BACKGROUND: Human immunodeficiency virus (HIV)-related mortality has decreased because of highly active antiretroviral therapy. As the life expectancy of HIV-infected patients has increased, the management of comorbid disease in such patients has become a more important concern. We examined the level of comfort self-reported by experts in HIV medicine with prescribing medications to HIV-infected patients for hyperlipidemia, diabetes, hypertension, and depression. METHODS: As part of a larger project (the Veterans Aging Cohort Study), physicians at infectious diseases (ID) clinics and physicians at general medical (GM) clinics were asked to complete a survey requesting information about demographic characteristics, training and certification received, and self-reported comfort with prescribing medications for patients with hyperlipidemia, diabetes, hypertension, and/or depression. Comfort was rated using a 5-point Likert scale, with scores of 4-5 classified as "comfortable." RESULTS: Of 150 attending physicians surveyed, 51 (34%) were ID certified, 33 (22%) were GM certified but practicing at an ID clinic, and 66 were GM certified and practicing at a GM clinic. Comorbid conditions were common among HIV-infected patients treated at the ID clinics (22% of these patients had hyperlipidemia, 17% had diabetes, 40% had hypertension, and 27% had depression). However, comfort with treating these conditions was less among physicians at the ID clinic. For example, comfort treating patients with hyperlipidemia was greater for GM-certified physicians at GM clinics than for GM-certified physicians and ID-certified physicians at ID clinics (98% vs. 73% and 71%, respectively; P < .0001 for trend). A similar pattern was seen for treating patients with diabetes and hypertension (P < .0001). Comfort with treating patients with depression was generally lower, particularly among physicians at ID clinics (P < .0001). CONCLUSIONS: We found that ID-certified physicians and GM-certified physicians at ID clinics reported less comfort prescribing medications for common comorbid conditions, compared with generalist physicians at GM clinics, despite a substantial prevalence of these conditions at the ID clinics. Methods are needed to increase physicians' level of comfort for prescribing treatment and/or to facilitate referral to other physicians for treatment.

Risk of diabetes in HIV infected veterans pre- and post-HAART and the role of HCV coinfection.

We examined the association of hepatitis C virus (HCV) infection with diabetes in veterans infected with human immunodeficiency virus (HIV) before and after the institution of highly active antiretroviral therapy (HAART). The role of age, race, liver disease, alcohol, and drug diagnoses upon the risk of diabetes was also determined. Male veterans with HIV who entered care between 1992 and 2001 were identified from the Veterans Affairs (VA) administrative database. Demographic and disease data were extracted. Kaplan-Meier curves were plotted to determine the incidence of diabetes. Unadjusted and adjusted hazards ratios for diabetes were determined using Cox regression method. A total of 26,988 veterans were studied. In multivariate Cox regression analysis, factors associated with a diagnosis of diabetes included increasing age (HR, 1.44 per 10-year increase in age; 95% CI, 1.39-1.49), minority race (African American: HR, 1.35; 95% CI, 1.24-1.48; Hispanic: HR, 1.63; 95% CI, 1.43-1.86), and care in the HAART era (HR, 2.35; 95% CI, 2.01-2.75). There was a significant interaction between care in the HAART era and HCV infection, with HCV infection being associated with a significant risk of diabetes in the HAART era (HR, 1.39; 95% CI, 1.27-1.53) but not in the pre-HAART era (HR, 1.01; 95% CI, 0.75-1.36). In conclusion, HIV-infected veterans in the HAART era are at a higher risk for diabetes compared with those in the pre-HAART era. HCV coinfection is associated with a significantly higher risk of diabetes in the HAART era, but not in the pre-HAART era. HCV-HIV coinfected patients should be aggressively screened for diabetes.

The Veterans Aging Cohort Study: observational studies of alcohol use, abuse, and outcomes among human immunodeficiency virus-infected veterans.

This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The organizers/chairs were Joseph Conigliaro and Amy Justice. The presentations were (1) Introduction, by Joseph Conigliaro and Tamra Madenwald; (2) Alcohol and HIV/AIDS: the importance of integrative and translational research, by Kendall Bryant; (3) Alcohol use and abuse among patients with HIV infection, by Joseph Conigliaro and Stephan Maisto; (4) Severity of comorbid alcohol use/abuse in HIV infection, by Amy Justice and Jeffrey Samet; (5) Estimating the impact of alcohol use on long-term HIV outcomes, by Scott Braithwaite and Amy Justice; (6) Homelessness, drug & alcohol use among HIV+ veterans, by Adam Gordon and Robert Cook; and (7) Hepatitis C & alcohol in the VACS 3 study, by Shawn Fultz and Kevin Kraemer. The symposium concluded with a discussion led and facilitated by Diedra Roach.

Testing, referral, and treatment patterns for hepatitis C virus coinfection in a cohort of veterans with human immunodeficiency virus infection.

We examined testing, referral, and treatment of patients with hepatitis C among HIV-infected patients in the Veterans Aging 3-Site Cohort Study by using patient- and provider-completed surveys and laboratory, pharmacy, and administrative records from the Department of Veterans Affairs electronic medical record. Of 881 human immunodeficiency virus-positive patients, 43% were coinfected with hepatitis C virus. Of these, 88 (30%) reported current alcohol consumption. Only one-third were counseled to reduce or stop alcohol consumption. Coinfected patients with indications for hepatitis C treatment had a high rate of contraindications, including both medical and psychiatric comorbidities. Of the 65 patients with indications for hepatitis C therapy and free of contraindications for treatment, only 18% underwent liver biopsy and 3% received IFN. Although treatment indications are common in this population, contraindications are also common. Health care providers are often unaware of alcohol consumption that may accelerate the course of hepatitis C, increase the risk of hepatocellular carcinoma, and reduce treatment efficacy.