Ties that bind: multiple relationships between clinical researchers and the pharmaceutical industry

BACKGROUND: It is believed that pharmaceutical industry sponsorship of clinical research leads to the development of multiple ties between clinicians and the pharmaceutical industry. To quantify this relationship we conducted a survey of medical specialists listed in the Medical Directory of Australia in 2002 and 2003. METHODS: A questionnaire was mailed that elicited information about all aspects of research relationships between clinicians and pharmaceutical companies. The odds of reporting multiple additional ties (financial and professional) with pharmaceutical companies by clinicians who had an active research relationship were compared with those who did not. All clinicians who returned a completed questionnaire about their research activities were included in the study. RESULTS: A questionnaire was mailed to 2120 medical specialists; 823 (39%) responded. Of these, 338 (41%) reported involvement in industry-sponsored research in the previous year. They were more likely than others to have been offered industry-sponsored items or activities valued at more than 500 AU dollars (>382 US dollars; odds ratio [OR], 3.5; 95% confidence interval [CI], 2.6-4.7) and support for attending international conferences (OR, 5.4; 95% CI, 3.9-7.4). The strongest associations were seen for acting as a paid consultant to industry (OR, 9.0; 95% CI, 3.9-20.4) and for membership on advisory boards (OR, 6.9; 95% CI, 5.1-9.6). There was a strong relationship between research collaboration and accumulation of industry ties. For 1 additional tie the OR was 2.2 (95% CI, 1.2-3.8) and rose to 6.3 (95% CI, 3.5-11.1) with 3 ties and 41.8 (95% CI, 14.5-143.4) with 6 or more ties. CONCLUSIONS: Medical specialists who have research relationships with the pharmaceutical industry are much more likely to have multiple additional ties than those who do not have research relationships. Institutional review should discourage clinical researchers from developing multiple ties.     

Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study

BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. METHODS: We investigated the frequency of and risk factors associated with liver-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death. RESULTS: There were 1246 deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver-related deaths were latest CD4 cell count (adjusted relative rate [RR], 16.1; 95% confidence interval [CI], 8.1-31.7 for <50 vs > or =500/microL), age (RR, 1.3; 95% CI, 1.2-1.4 per 5 years older), intravenous drug use (RR, 2.0; 95% CI, 1.2-3.4), HCV infection (RR, 6.7; 95% CI, 4.0-11.2), and active HBV infection (RR, 3.7; 95% CI, 2.4-5.9). Univariable analyses showed no relationship between cumulative years patients were receiving cART and liver-related death (RR, 1.00; 95% CI, 0.93-1.07). Adjustment for the most recent CD4 cell count and patient characteristics resulted in an increased risk of liver-related mortality per year of mono or dual antiretroviral therapy before cART (RR, 1.09; 95% CI, 1.02-1.16; P = .008) and per year of cART (RR, 1.11; 95% CI, 1.02-1.21; P = .02). CONCLUSIONS: Liver-related death was the most frequent cause of non-AIDS-related death. We found a strong association between immunodeficiency and risk of liver-related death. Longer follow-up is required to investigate whether clinically significant treatment-associated liver-related mortality will develop.     

Encounters with pharmaceutical sales representatives among practicing internists.

BACKGROUND: Although pharmaceutical sales representatives provide physicians with information on new products, these encounters have rarely been studied in practice settings. We examined these interactions among practicing internists and assessed whether prior residency policies limiting pharmaceutical sales representative access affected the subsequent behavior of practitioners. METHODS: We conducted a mail survey of the internal medicine staffs of a medical school hospital and two affiliated community hospitals. A second request was sent to nonresponders. After the second mailing, a random sample of nonresponders was compared with a similar sample of respondents. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression. RESULTS: Of the 346 (40%) internists who responded, 22% were women and 60% were trained in university hospitals. There were no differences in gender, subspecialization, or type of training when survey responders and nonresponders were compared. Two hundred eighty-seven (83%) physicians had met with pharmaceutical sales representatives within the previous year, of whom 248 (86%) had received drug samples. Having had a policy that limited access to pharmaceutical sales representatives during residency did not affect the subsequent likelihood of seeing these representatives (P = 0.20) or accepting samples in practice (P = 0.99). Those describing themselves as busy practitioners were significantly less likely to abstain from meeting pharmaceutical sales representatives (OR = 0.2, 95% CI: 0.1 to 0.6, P <0.001). Those with very frequent contacts (>10 times/month) were virtually all busy practitioners. CONCLUSIONS: Encounters between physicians and pharmaceutical sales representatives are common in internal medicine practice, especially in busy offices. Policies designed to limit pharmaceutical sales representative access during residency do not appear to affect the subsequent likelihood of meeting with pharmaceutical sales representatives or accepting samples.     

Predictors of treatment in patients with chronic hepatitis C infection - role of patient versus nonpatient factors

Treatment with interferon and ribavirin is effective in patients with chronic infection with hepatitis C virus (HCV). Previous data indicate that treatment rates are suboptimal. We sought to identify patient and provider-level predictors of treatment receipt in HCV by conducting a retrospective cohort study of 5701 HCV patients in a large regional Veteran's Administration (VA) healthcare network. We also determined the degree of variation in treatment rates attributable to patient, provider, and facility factors. Three thousand seven hundred forty-three patients (65%) were seen by a specialist and 894 (15.7%) received treatment. Treatment rates varied from 6% to 29% across the 5 facilities included in the analysis. Patients were less likely to receive treatment if they were older [RR, 0.55; 95% CI, 0.45, 0.67), single (RR, 0.77; 95%CI, 0.67, 0.88), had hepatic dysfunction (RR, 0.73; 95%CI, 0.66, 0.89), had normal alanine aminotransferase (ALT) (RR, 0.73; 95%CI, 0.59, 0.89), had HCV genotype 1 (RR, 0.78; 95%CI, 0.71, 0.86), were African American with genotype 1 (RR, 0.78; 95% CI, 0.71, 0.86), or were anemic (RR, 0.70; CI, 0.60, 0.89). In addition, patients evaluated by less experienced providers were 77% less likely to receive treatment than those evaluated by more experienced providers. The patient, provider, and facility factors explained 23%, 25%, and 7% of variation in treatment rates, respectively. Conclusion: These data suggest that although patient characteristics are important predictors of treatment in HCV, a significant proportion of variation in treatment rates is explained by provider factors. These potentially modifiable provider-level factors may serve as high-yield targets for future quality improvement initiatives in HCV.     

Foetal and childhood exposure to famine and the risks of cardiometabolic conditions in adulthood: A systematic review and meta‐analysis of observational studies

A systematic review and meta‐analysis of observational studies was performed to provide a deeper understanding of the associations between foetal and childhood exposure to famine and the risks of type 2 diabetes mellitus (T2DM), metabolic syndrome, hypertension, hyperglycaemia, dyslipidaemia, obesity, overweight, coronary heart disease, stroke, and nonalcoholic fatty liver disease (NAFLD) in adulthood. Both foetal and childhood exposure to famine were positively associated with the risks of T2DM (foetal exposure: RR 1.37, 95% CI, 1.23‐1.52; childhood exposure: RR 1.33, 95% CI, 1.08‐1.64), metabolic syndrome (RR 1.26, 95% CI, 1.07‐1.50; RR 1.24, 95% CI, 1.13‐1.35), hypertension (RR 1.30, 95% CI, 1.07‐1.57; RR 1.33, 95% CI, 1.02‐1.74), hyperglycaemia (RR 1.27, 95% CI, 1.11‐1.45; RR 1.25, 95% CI, 1.10‐1.42), dyslipidaemia (RR 1.48, 95% CI, 1.33‐1.66; RR 1.27, 95% CI, 1.12‐1.45), obesity (RR 1.19, 95% CI, 1.02‐1.39; RR 1.13, 95% CI, 1.00‐1.28), overweight (RR 1.17, 95% CI, 1.07‐1.29; RR 1.07, 95% CI, 1.00‐1.14), coronary heart disease (RR 1.22, 95% CI, 1.00‐1.51; RR 1.21, 95% CI, 1.09‐1.35), and moderate‐to‐severe NAFLD (RR 1.66, 95% CI, 1.07‐2.57; RR 1.68, 95% CI, 1.41‐1.99) in adulthood. No association was observed for the risks of stroke or mild NAFLD. Adjustments for age, alcohol, smoking, body mass index, and physical activity nullified some associations. The associations were generally stronger in women than in men. In summary, foetal and childhood exposure to famine may confer greater risks of developing certain cardiometabolic conditions in adulthood, particularly in women. The extent to which risks for cardiometabolic conditions are associated with early‐life famine appears to be determined by certain factors in adulthood.     

Increased Risk of Age-Related Macular Degeneration with Chronic Hepatitis C Virus Infection: A Nationwide Population-Based Propensity Score-Matched Cohort Study in Taiwan

Studies evaluating the association between age-related macular degeneration (AMD) risk and HCV infection are scant. In this population-based cohort study, 13,300 patients newly diagnosed as having HCV (HCV cohort) and 26,600 propensity score-matched patients without HCV (non-HCV cohort) were identified from the Taiwan National Health Insurance Research Database between 2000 and 2013. Furthermore, 1,983 patients with HCV who received pegylated interferon and ribavirin treatment (HCV-treated cohort) and propensity score-matched patients with HCV (matched at a ratio of 1:2) who did not receive this treatment (HCV-untreated cohort) were selected from the HCV cohort. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) associated with the risk of AMD in the HCV and non-HCV cohorts. The adjusted HR (aHR) for AMD in the HCV cohort was 1.22 (95% CI = 1.09–1.35). This significant association was observed only for nonexudative AMD (aHR = 1.22, 95% CI = 1.09–1.37). Compared with the HCV-untreated cohort, the HCV-treated cohort showed no significant association with any type of AMD (aHR = 1.07, 95% CI = 0.81–1.43). Age and sex did not modify AMD development after the exposure and treatment of chronic HCV infection. Our findings revealed that patients with chronic HCV infection had an increased risk of AMD.     

Impact of hepatitis C infection on long-term mortality of injecting drug users from 1990 to 2002: differences before and after HAART

OBJECTIVE: To assess the impact of HIV and hepatitis C virus (HCV) infection on long-term mortality in injecting drug users (IDU). DESIGN: Community-based prospective cohort study. METHODS: Mortality data from follow-up in clinical sites and the Mortality Registry by December 2002 were collected for 3247 IDU who attended three centres for voluntary counselling and testing for HIV/AIDS, HCV and hepatitis B virus (HBV) in 1990-1996. Mortality rates by Poisson regression were adjusting for age, sex, duration of drug use, education, HBV and calendar period (1990-1997 and 1998-2002). RESULTS: Overall, 11.2% were HIV/HCV negative, 43.7% positive only for HCV and 45.1% positive for both. During 26 772 person-years of follow-up, 585 deaths were detected (2.19/100 person-years). Before 1997, HIV/HCV-positive subjects had a five-fold increase in risk of death [relative risk (RR), 5.4; 95% confidence interval (CI), 2.5-11.4] compared with those negative for both; after 1997, a three-fold increase was observed (RR, 2.7; 95% CI, 1.7-4.2). Being HCV positive/HIV negative was not associated with an increase in the risk of death either before (RR, 1.3; 95% CI, 0.6-2.9) or after (RR, 1.2; 95% CI, 0.8-1.9) 1997 compared with HCV/HIV negative. While increases in mortality were seen in those HCV/HIV negative (RR, 1.6; 95% CI, 0.7-3.7) and those only positive for HCV (RR, 1.5; 95% CI, 1.0-2.1), a 20% reduction among coinfected IDUs was observed after 1997 (interaction P = 0.033). CONCLUSIONS: HCV/HIV coinfection has had a large impact on mortality in IDU. After 1997, mortality increased in HIV negative/HCV positive subjects and decreased in HIV positive/HCV positive.     

Younger age potentiates post myocardial infarction survival disadvantage of women

BACKGROUND: Female patients with acute myocardial infarction (MI) exhibit higher unadjusted in-hospital mortality rates compared to male patients. However, contradictory evidence exists on whether this survival disadvantage disappears after adjustment for age and other prognostic factors. This study, based on a countrywide survey of consecutive unselected patients with acute MI, examined whether female gender is an independent predictor of poor short-term outcome and less intensive in-hospital treatment. METHODS: Data on a total of 7433 patients were analyzed. RESULTS: The mean age was 64+/-13 years and the proportion of females in this population was 23%. Univariate and multivariate predictors of in-hospital mortality in female patients were estimated. Unadjusted in-hospital mortality rates of women were significantly higher compared to men (17.7 vs. 8.6, p<0.001). In multivariate analysis, female gender was an independent predictor of in-hospital mortality in the total population [relative risk (RR)=1.29, 95% confidence interval (CI)=1.02-1.64, p=0.036]. The RR of women for in-hospital death was exaggerated among younger patients, aged <55 years (RR=3.84, 95% CI=1.07-13.74, p=0.039). Female gender was also independently and inversely associated with administration of thrombolytic treatment (RR=0.724, 95% CI=0.630-0.831, p=<0.001). CONCLUSION: Although female gender is an independent predictor of higher post-MI in-hospital mortality with a pronounced effect among younger patients, women are less likely to receive thrombolysis than men. Based on the results from this countrywide study, we should consider women, especially of younger age, as patients at particular high risk, who contrary to common practice, deserve more intensive and aggressive in-hospital treatment.     

Physician specialty and mortality among elderly patients hospitalized with heart failure

BACKGROUND: Whether specialty care improves survival among patients with heart failure remains controversial. METHODS: We evaluated specialty care and outcomes in 25869 Medicare beneficiaries hospitalized with heart failure in the United States from 1998 through 1999. Patients were classified based on the specialty of their attending physician: cardiologist, internist, general physician, or family physician. The primary outcome of interest was all-cause mortality within 30 days of admission. RESULTS: Cardiologists were attending physicians for 26%, internists for 50%, and general and family physicians cared for the remainder. Mortality at 30 days was lowest for patients cared for by cardiologists (8.8%), higher for patients cared for by internists (10.0%, relative risk [RR] = 1.07; 95% confidence interval [CI]: 0.97 to 1.19; P = 0.059) and general physicians (11.1%, RR = 1.26; 95% CI: 0.99 to 1.58; P = 0.086), and highest for patients cared for by family physicians (12.0%, RR = 1.31; 95% CI: 1.15 to 1.49; P <0.001). Patients cared for by family physicians remained at higher 30-day mortality rates whether with (RR = 1.30; 95% CI: 1.11 to 1.52) or without consultation with cardiologists (RR = 1.31; 95% CI: 1.13 to 1.52). CONCLUSION: Hospitalized patients with heart failure had lower 30-day mortality when treated by cardiologists than when they were treated by other physicians. Although these differences were modest (RR = 1.07) for internists, they were substantial for general physicians (RR = 1.26) and family physicians (RR = 1.31); of note was that inpatient cardiology consultation did not appear to change this relation.     

Lipid abnormalities in HIV/hepatitis C virus-coinfected patients

BACKGROUND: Among HIV-infected patients, hepatitis C virus (HCV) coinfection is associated with increased rates of lipodystrophy and insulin resistance. Its impact on HIV-associated dyslipidaemia is less clear. METHODS: The lipid profiles of all HIV-infected patients and a subset of HCV-infected patients seen at the VA Medical Center in Dallas from January 2003 to March 2004 were analysed. Demographic data, HCV serostatus, and HIV treatment history were recorded. Lipid profiles of HIV/HCV-coinfected patients were compared with those of HIV-monoinfected and HCV-monoinfected patients. RESULTS: A total of 359 HIV-infected patients, 91 (25.3%) of whom were HCV coinfected, and 112 HCV-infected patients were included in the analysis. Among the HIV-infected patients, HCV coinfection was associated with a reduced risk of hypercholesterolaemia [9.9% vs 24.8%; relative risk (RR)=0.333; 95% confidence interval (CI)=0.158-0.699; P<0.001] and hypertriglyceridaemia (48.4% vs 60.3%; RR=0.616; 95% CI=0.382-0.994; P=0.031). After controlling for duration of protease inhibitor (PI) therapy, race, alanine aminotransferase (ALT) concentration and platelet count, HCV remained an independent predictor of hypercholesterolaemia (RR=0.369; P=0.01) and any dyslipidaemia (RR=0.531; P=0.019). In addition, the rate of dyslipidaemias was lower among HCV-monoinfected than HIV/HCV-coinfected patients (29.5% vs 50.5; P=0.002). White race was also an independent predictor of dyslipidaemia (73.8% vs 50.7%; RR=2.32; 95% CI=1.44-3.76; P=0.001). CONCLUSIONS: HCV coinfection independently predicted lower rates of dyslipidaemia among HIV-infected patients. An analysis of lipid kinetics among mono- and coinfected patients may elucidate the mechanisms of the apparent protective effect of HCV infection.     

Alcohol industry sponsorship and hazardous drinking among sportspeople

Aims To examine the nature and extent of alcohol industry sponsorship of sportspeople, and its association with drinking. Methods A purposive sample of participants (n = 1279) from various sporting codes were asked whether they personally, their team, or club received free and/or discounted alcohol or funding from an alcohol industry body (e.g. pub, brewery, wholesaler); how much they received; and whether they felt they should drink their sponsor's product and/or at the sponsor's premises. Drinking behaviour was assessed with the Alcohol Use Disorders Identification Test (AUDIT) questionnaire. Findings Alcohol industry sponsorship was reported by 47.8% of the sample. Of those sponsored, 47% reported receiving free and/or discounted alcohol products. In multivariate models, those receiving sponsorship at the individual, team and club level had AUDIT scores that were, on average, 2.4 points higher [95% confidence interval (CI): 0.70–4.09] than those who received no sponsorship. Receiving free and/or discounted alcohol (β_adj = 0.95, 95% CI: 0.01–1.88) and feeling that they should go to the sponsor's pub/club to drink (β_adj = 1.91, 95% CI: 0.85–2.98) were also associated with higher AUDIT scores. Provision of free or discounted alcoholic beverages was associated more strongly with AUDIT scores (β_adj = 1.56; 95% CI: 0.62–2.51) than other forms of sponsorship from the alcohol industry (e.g. provision of uniforms). Conclusions Alcohol industry sponsorship of sportspeople, and in particular the provision of free or discounted alcoholic beverages, is associated with hazardous drinking after adjustment for a range of potential confounders. Sports administration bodies should consider the health and ethical risks of accepting alcohol industry sponsorship.     

Hepatitis C virus infection, HBsAg carrier state and hepatocellular carcinoma: relative risk and population attributable risk from a case-control study in Italy.

In 1990, a case-control study was conducted in Italy to investigate the possible association between HCV infection and hepatocellular carcinoma (HCC). Serum samples from 65 subjects with newly diagnosed hepatocellular carcinoma and 99 hospital control subjects were tested for the presence of anti-HCV by second-generation ELISA test; positive sera were assayed by RIBA anti-HCV second-generation test. In addition, samples were tested for hepatitis B surface antigen (HBsAg), antibodies to the hepatitis B core antigen (anti-HBc), and antibodies to HBsAg (anti-HBs). The presence of HCV and/or HBsAg serologic markers was significantly associated with hepatocellular carcinoma risk: the relative risk (RR) of HCC was 21.3 (95% CI = 8.8-51.5) for anti-HCV positivity in the absence of HBsAg; the relative risk of HCC was 13.3 (95% CI = 5.5-32.2) for the presence of HBsAg in the absence of anti-HCV. A higher risk (77.0) was observed when both markers were present. These findings indicate that HCV and HBsAg are independent risk factors for HCC. The results of multivariate analysis showed that the adjusted RR linking anti-HCV and HCC was 26.9 (95% CI = 9.9-72.5), the adjusted RR linking HBsAg and HCC was 11.4 (95% CI = 3.1-41.4), whereas no association (RR 1.5; 95% CI = 0.6-3.6) was found to link HCC with anti-HBc and/or anti-HBs positivity. Through the computation of population attributable risk we estimate that 25% of HCC cases occurring in Italy could be attributed to anti-HCV positivity alone and 20% to HBsAg carrier state alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of human immunodeficiency virus infection on progression to end-stage liver disease in individuals with hemophilia and hepatitis C virus infection

Hepatitis C virus (HCV) is the major cause of chronic liver disease in hemophiliacs. To determine the effect of human immunodeficiency virus (HIV) on the natural history of HCV infection, we evaluated end-stage liver disease (ESLD) in 157 hemophiliacs (85 HIV positive and 72 HIV negative) with HCV infection for an average of 24 years. After adjusting for age at HCV infection, past or current hepatitis B surface antigen positivity, and history of alcohol abuse, we determined that the rate of ESLD was significantly greater among HIV-positive than among HIV-negative hemophiliacs (relative risk [RR], 3.72; 95% confidence interval [CI], 1.25-11.09), as was the adjusted RR for death due to ESLD (RR, 3.81; 95% CI, 1.19-12.16). Among HIV-positive hemophiliacs, crude RR for ESLD was lower, but not significantly so, with antiretroviral treatment (RR, 0.19; 95% CI, 0.03-1.14; P=.069) and increased with each decade of HCV infection (RR, 2.26; 95% CI, 1.42-3.59; P=.0006) and HIV infection (RR, 2.18; 95% CI, 1.36-3.49; P=.0013). These findings suggest that HIV accelerates HCV disease progression.     

Is the increased risk of liver enzyme elevation in patients co-infected with HIV and hepatitis virus greater in those taking antiretroviral therapy?

OBJECTIVES: To investigate if the risk of liver enzyme elevation (LEE) in HIV/hepatitis B or C (HBV, HCV) co-infection is altered by HAART (two or more drugs). METHODS: Analysis comprised HIV-positive patients in the ICoNA study without acute hepatitis who had >or= 1 positive HCV antibody test and > 1 positive HBV surface antigen test. LEE was defined as > 5x baseline alanine aminotransferase (ALT) or > 3.5x baseline if the baseline was > 40 IU/l. Analysis used Poisson regression with generalized estimating equation correction to examine HBV or HCV co-infection, use of HAART, baseline ALT and demographics as LEE predictors. RESULTS: Of the 5272 patients, 47.6% were co-infected with HCV/HBV; 29.9% were female and 39% were intravenous drug users. There were 275 episodes of LEE during 18 259 person-years follow up. Taking HAART did not significantly increase risk of LEE [adjusted relative risk (RR), 1.19; 95% confidence interval (CI), 0.81-1.75; P = 0.37]. Co-infection increased the risk of LEE (adjusted RR, 5.07; 95% CI, 3.47-7.48; P < 0.001), with no significant differences if taking HAART (adjusted RR, 4.99; 95% CI, 3.38-7.37) or not (adjusted RR, 6.02; 95% CI, 2.02-17.98) (P = 0.74 for interaction). Females were at lower risk of LEE than males (adjusted RR, 0.59; 95% CI, 0.42-0.83; P = 0.02). CONCLUSIONS: HIV and HBV/HCV co-infection per se is associated with increased risk of LEE that is not modified by HAART. The recommendation for caution in HAART use in co-infected patients, simply based on a high rate of LEE in people on therapy, may be questionable.     

Prevalence of hepatitis C and coinfection with HIV among United States veterans in the New York City metropolitan area

OBJECTIVES: The aims of this study were to determine the prevalence of hepatitis C virus (HCV) infection and its risk factors, as well as the prevalence of coinfection with HIV and its risk factors, among patients with confirmed HCV infection. METHODS: In a 1-day cross-sectional HCV survey at six Veterans Affairs Medical Centers in the New York City metropolitan area, all 1943 patients undergoing phlebotomy for any reason were asked to be tested for HCV antibody by enzyme immumoassay (EIA). A total of 1098 patients (57%) agreed to HCV testing, 1016 of whom also completed a questionnaire on demographics and HCV risk factors. All HCV EIA(+) samples were confirmed by HCV RNA and HCV recombinant immunoblot assay (RIBA) antibody testing and were also tested for HCV viral load, HCV genotype, and antibodies to HIV in a blinded fashion. RESULTS: The prevalence of confirmed HCV infection was 10.6% (95% CI = 8.7-12.4%), and the prevalence of HCV viremia was 8.2% (95% CI = 6.6-9.8%). The rate of HCV viremia among anti-HCV(+) patients was 77.6%, and HCV genotype 1 was present in 87.5% of viremic patients. Independent risk factors for HCV infection were injection drug use (OR = 35.6, 95% CI = 16.9-75.2), blood exposure during combat (OR = 2.6, 95% CI = 1.2-5.7), alcohol abuse (OR = 2.4; 95% CI = 1.2-4.8), and service in the Vietnam era (OR = 2.1; 95% CI = 1.0-4.5). Coinfection with HIV was present in 24.8% of anti-HCV(+) patients. The only independent risk factor for coinfection was age <50 yr (OR = 3.7, 95% CI = 1.1-12.1). CONCLUSIONS: U.S. veterans who are receiving medical care at VA medical centers in the New York City metropolitan area have a much higher rate of chronic hepatitis C than the general population, with a high frequency of genotype 1. Coinfection with HIV is very common in patients with confirmed HCV infection, and these patients should routinely be offered HIV testing.     

Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy

OBJECTIVE: To assess hepatitis C virus (HCV) antibody prevalence in the EuroSIDA cohort, along with survival, human immunodeficiency virus (HIV)-1 disease progression, virologic response (plasma HIV-1 RNA load of < 500 copies/mL), and CD4 cell count recovery by HCV serostatus in patients initiating highly active antiretroviral therapy (HAART). RESULTS: HCV serostatus at or before enrollment was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive and seronegative, respectively. No association between an increased incidence of acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus was seen after adjustment for other prognostic risk factors known at baseline (adjusted incidence rate ratio [IRR], 0.97 [95% confidence interval {CI}, 0.81-1.16]). However, there was a large increase in the incidence of liver disease-related deaths in HCV-seropositive patients in adjusted models (IRR, 11.71 [95% CI, 6.42-21.34]). Among 2260 patients of known HCV serostatus initiating HAART, after adjustment, there was no significant difference between HCV-seropositive and -seronegative patients with respect to virologic response (relative hazard [RH], 1.13 [95% CI, 0.84-1.51]) and immunologic response, whether measured as a > or = 50% increase (RH, 0.94 [95% CI, 0.77-1.16]) or a > or = 50 cells/microL increase (RH, 0.92 [95% CI, 0.77-1.11]) in CD4 cell count after HAART initiation. CONCLUSIONS: HCV serostatus did not affect the risk of HIV-1 disease progression, but the risk of liver disease-related deaths was markedly increased in HCV-seropositive patients. The overall virologic and immunologic responses to HAART were not affected by HCV serostatus.     

Profile of patients triply infected with HIV and the hepatitis B and C viruses in the HAART era

HIV-HCV-HBV-coinfected patients were assessed to characterize the viral interactions in the setting of HIV coinfection and in the HAART era. All positive anti-HCV antibody and HBs antigen-positive HIV-infected patients were identified at five HIV clinics. Antihepatitis delta (HDV) antibody, serum HIV RNA, HCV RNA, and HBV DNA quantification and genotype determinations were performed. Out of 67 patients identified 47 (70%) were receiving anti-HBV therapy. HCV RNA and HBV DNA were detectable in 52.5% and 37% of patients, respectively. All possible patterns were found, regardless of anti-HBV therapy. HDV coinfection was associated with undetectable HCV RNA [RR 9.52 (95% CI 1.85-49.01); p = 0.007]. Independent factors predicting undetectable HBV DNA lacked HBeAg [RR 13.94 (95% CI 3.05-63.72); p = 0.001] and use of anti-HBV therapy [RR 11.42 (95% CI 2.43-53.54); p = 0.002]. Replication and genotypes of HCV or HBV had no impact on the replication of the other virus. In conclusion, in this cohort of triple infection (HBV/HCV/HIV) various viral patterns were identified. Spontaneous HCV clearance was frequent, and it was independently associated with HDV coinfection. In the absence of HBV therapy, HBV most often actively replicates. HBV/HCV replication or genotypes were not related to the replication of the other virus.