Human Immunodeficiency Virus (HIV); lung cancer; incidence; smoking; immunosuppression; non-AIDS defining malignancy
Doxorubicin-loaded micelles were prepared from a copolymer comprising cholic acid (CA) and polyethyleneimine (PEI) for the delivery of antitumor drugs. The CA-PEI copolymer was synthesized via pairing mediated by N,N’-dicyclohexylcarbodiimide and N-hydroxysuccinimide using dichloromethane as a solvent. Fourier transform infrared and nuclear magnetic resonance analyses were performed to verify the formation of an amide linkage between CA and PEI and doxorubicin localization into the copolymer. Dynamic light scattering and transmission electron microscopy studies revealed that the copolymer could self-assemble into micelles with a spherical morphology and an average diameter of <200 nm. The CA-PEI copolymer was also characterized by X-ray diffraction and differential scanning calorimetry. Doxorubicin-loaded micelles were prepared by dialysis method. A drug release study showed reduced drug release with escalating drug content. In a cytotoxicity assay using human colorectal adenocarcinoma (DLD-1) cells, the doxorubicin-loaded CA-PEI micelles exhibited better antitumor activity than that shown by doxorubicin. This is the first study on CA-PEI micelles as doxorubicin carriers, and this study demonstrated that they are promising candidates as carriers for sustained targeted antitumor drug delivery system.
Micelles; Nanoparticles; Cholic acid; Polyethyleneimine; Doxorubicin
We assessed smoking data from the Veterans Health Administration (VHA) electronic medical record (EMR) Health Factors dataset.
To assess the validity of the EMR Health Factors smoking data, we first created an algorithm to convert text entries into a 3-category smoking variable (never, former, and current). We compared this EMR smoking variable to 2 different sources of patient self-reported smoking survey data: (a) 6,816 HIV-infected and -uninfected participants in the 8-site Veterans Aging Cohort Study (VACS-8) and (b) a subset of 13,689 participants from the national VACS Virtual Cohort (VACS-VC), who also completed the 1999 Large Health Study (LHS) survey. Sensitivity, specificity, and kappa statistics were used to evaluate agreement of EMR Health Factors smoking data with self-report smoking data.
For the EMR Health Factors and VACS-8 comparison of current, former, and never smoking categories, the kappa statistic was .66. For EMR Health Factors and VACS-VC/LHS comparison of smoking, the kappa statistic was .61.
Based on kappa statistics, agreement between the EMR Health Factors and survey sources is substantial. Identification of current smokers nationally within the VHA can be used in future studies to track smoking status over time, to evaluate smoking interventions, and to adjust for smoking status in research. Our methodology may provide insights for other organizations seeking to use EMR data for accurate determination of smoking status.
Chronic inflammation caused by hepatitis B virus infection, hepatitis C virus infection, and/or heavy alcohol use can lead to fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). FIB-4 is an index score calculated from platelet count, alanine transaminase, aspartate transaminase, and age that predicts fibrosis and cirrhosis. We hypothesized that high FIB-4 would be associated with development of HCC in HIV-infected persons, who are at high risk due to high prevalence of viral hepatitis and alcohol consumption, and possibly due to HIV infection itself.
Using proportional hazards models, we tested this hypothesis among 22,980 HIV-infected men from the Veterans Aging Cohort Study. We identified incident HCC cases from the VA Central Cancer Registry.
During follow-up, there were 112 incident HCC diagnoses. The age-and race/ethnic group-adjusted HR was 4.2 (95% CI: 2.4, 7.4)for intermediate FIB-4 and 13.0 (95% CI: 7.2, 23.4) for high FIB-4, compared to low FIB-4. After further adjustment for enrollment year, CD4 count, HIV-1 RNA level, antiretroviral therapy use, hepatitis B and C virus infection, alcohol abuse/dependency, and diabetes, FIB-4 remained a strong, significant, independent risk factor for HCC. The multivariate-adjusted HR was 3.6 (95% CI: 2.1, 6.4) for intermediate FIB-4 and 9.6 (95% CI: 5.2, 17.4) for high FIB-4.
Calculated from routine, non-invasive laboratory tests, FIB-4 is a strong, independent HCC risk factor in HIV-infected patients.
FIB-4 might prove valuable as an easily measured index to identify those at highest risk for HCC, even prior to development of clinical cirrhosis.
hepatocellular carcinoma; FIB-4; HIV; liver neoplasms; hepatic fibrosis
The absence of validated methods to identify hepatic decompensation in cohort studies has prevented a full understanding of the natural history of chronic liver diseases and impact of medications on this outcome. We determined the ability of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events within the Veterans Aging Cohort Study (VACS).
Medical records of patients with hepatic decompensation codes and/or laboratory abnormalities of liver dysfunction (total bilirubin ≥5.0 gm/dL, albumin ≤2.0 gm/dL, international normalized ratio ≥1.7) recorded one year before through six months after VACS entry were reviewed to identify decompensation events (i.e., ascites, spontaneous bacterial peritonitis, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma) at VACS enrollment. Positive predictive values (PPVs) of diagnostic codes, laboratory abnormalities, and their combinations for confirmed outcomes were determined.
Among 137 patients with a hepatic decompensation code and 197 with a laboratory abnormality, the diagnosis was confirmed in 57 (PPV, 42%; 95% CI, 33% – 50%) and 56 (PPV, 28%; 95% CI, 22% – 35%), respectively. The combination of any code plus laboratory abnormality increased PPV (64%; 95% CI, 47% - 79%). One inpatient or ≥2 outpatient diagnostic codes for ascites, spontaneous bacterial peritonitis, or variceal hemorrhage had high PPV (91%; 95% CI, 77% – 98%) for confirmed hepatic decompensation events.
An algorithm of 1 inpatient or ≥2 outpatient codes for ascites, peritonitis, or variceal hemorrhage has sufficiently high PPV for hepatic decompensation to enable its use for epidemiologic research in VACS. This algorithm may be applicable to other cohorts.
hepatic decompensation; end-stage liver disease; epidemiologic methods; outcomes; validation studies
Whether hepatitis C (HCV) confers additional coronary heart disease (CHD) risk among Human Immunodeficiency Virus (HIV) infected individuals is unclear. Without appropriate adjustment for antiretroviral therapy, CD4 count, and HIV-1 RNA, and substantially different mortality rates among those with and without HIV and HCV infection, the association between HIV, HCV, and CHD may be obscured.
Methods and Results
We analyzed data on 8579 participants (28% HIV+, 9% HIV+HCV+) from the Veterans Aging Cohort Study Virtual Cohort who participated in the 1999 Large Health Study of Veteran Enrollees. We analyzed data collected on HIV and HCV status, risk factors for and the incidence of CHD, and mortality from 1/2000–7/2007. We compared models to assess CHD risk when death was treated as a censoring event and as a competing risk. During the median 7.3 years of follow-up, there were 194 CHD events and 1186 deaths. Compared with HIV−HCV− Veterans, HIV+ HCV+ Veterans had a significantly higher risk of CHD regardless of whether death was adjusted for as a censoring event (adjusted hazard ratio (HR)=2.03, 95% CI=1.28–3.21) or a competing risk (adjusted HR=2.45, 95% CI=1.83–3.27 respectively). Compared with HIV+HCV− Veterans, HIV+ HCV+ Veterans also had a significantly higher adjusted risk of CHD regardless of whether death was treated as a censored event (adjusted HR=1.93, 95% CI=1.02–3.62) or a competing risk (adjusted HR =1.46, 95% CI=1.03–2.07).
HIV+HCV+ Veterans have an increased risk of CHD compared to HIV+HCV−, and HIV−HCV− Veterans.
viruses; coronary disease; mortality; multi morbidity
It is unknown whether extended treatment with pegylated interferon (PEG) and weight-based ribavirin (WBR) results in higher rates of sustained virologic response (SVR) among HCV-HIV coinfected patients compared with standard duration therapy.
The study aimed to measure rates of SVR among coinfected patients who received extended therapy with PEG plus WBR.
HCV-HIV coinfected subjects were treated with PEG and WBR, and those who achieved early virologic response (EVR; ≥2 log decrease in HCV RNA from baseline or HCV RNA<600 IU/mL) at week 12 were eligible to continue treatment for 72 weeks. SVR (HCV RNA<60 IU/mL) was measured 24 weeks after treatment discontinuation. Predictors of SVR were assessed in simple and multivariate logistic regression.
A total of 329 subjects enrolled at 36 sites. Of 184 subjects who achieved EVR, 169 entered Step 3: 89% male, 52% White, 29% Black, and 71% HCV treatment naïve. The overall SVR rate was 27% (95% CI, 22%–32%) among all subjects, and 33% (95% CI, 27%–40%) among the 223 who were HCV treatment naïve. In exploratory analyses, among 120 treatment-naïve subjects who entered Step 3, the SVR rate was 62% (95% CI, 52%–70%). In this subgroup, predictors of SVR were HCV genotype 2 or 3 (P = .03), HCV RNA <800,000 IU/mL at study entry (P = .05), and achievement of complete EVR (HCV RNA<600 IU/mL at week 12; P < .0001).
Among all subjects, we observed a comparable overall SVR rate to prior studies of subjects treated for 48 weeks. Extended treatment with PEG and WBR may be beneficial to subsets of coinfected patients, specifically those who are treatment naïve and achieve complete EVR.
extended therapy; HCV; HIV; weight-based ribavirin
Rationale: In aging HIV-infected populations comorbid diseases are important determinants of morbidity and mortality. Pulmonary diseases have not been systematically assessed in the combination antiretroviral therapy (ART) era.
Objectives: To determine the incidence of pulmonary diseases in HIV-infected persons compared with HIV-uninfected persons.
Methods: We analyzed data from the Veterans Aging Cohort Study Virtual Cohort, consisting of 33,420 HIV-infected veterans and 66,840 age, sex, race and ethnicity, and site-matched HIV-uninfected veterans. Using Poisson regression, incidence rates and adjusted incidence rate ratios were calculated to determine the association of HIV with pulmonary disease. The Virtual Cohort was merged with the 1999 Veterans Large Health Survey to adjust for self-reported smoking in a nested sample (14%).
Measurements and Main Results: Incident chronic obstructive pulmonary disease, lung cancer, pulmonary hypertension, and pulmonary fibrosis, as well as pulmonary infections, were significantly more likely among HIV-infected patients compared with uninfected patients in adjusted analyses, although rates of asthma did not differ by HIV status. Bacterial pneumonia and chronic obstructive pulmonary disease were the two most common incident pulmonary diseases, whereas opportunistic pneumonias were less common. Absolute rates of most pulmonary diseases increased with age, although the relative differences between those with and without HIV infection were greatest in younger persons. Chronic obstructive pulmonary disease and asthma, as well as pulmonary infections, were less likely in those with lower HIV RNA levels and use of ART at baseline.
Conclusions: Pulmonary diseases among HIV-infected patients receiving care within the Veterans Affairs Healthcare System in the combination ART era reflect a substantial burden of non–AIDS-defining and chronic conditions, many of which are associated with aging.
HIV; respiratory tract diseases; lung diseases, obstructive; pneumonia; pneumonia, bacterial
HIV clinical care now involves prevention and treatment of age-associated comorbidity. Although physical function is an established correlate to comorbidity in older adults without HIV infection, its role in aging of HIV-infected adults is not well understood. To investigate this question we conducted cross-sectional analyses including linear regression models of physical function in 3227 HIV-infected and 3240 uninfected patients enrolled 2002–2006 in the Veterans Aging Cohort Study-8-site (VACS-8). Baseline self-reported physical function correlated with the Short Form-12 physical subscale (ρ = 0.74, p < 0.001), and predicted survival. Across the age groups decline in physical function per year was greater in HIV-infected patients (βcoef −0.25, p < 0.001) compared to uninfected patients (βcoef −0.08, p = 0.03). This difference, although statistically significant (p < 0.01), was small. Function in the average 50-year old HIV-infected subject was equivalent to the average 51.5-year-old uninfected subject. History of cardiovascular disease was a significant predictor of poor function, but the effect was similar across groups. Chronic pulmonary disease had a differential effect on function by HIV status (Δβcoef −3.5, p = 0.03). A 50-year-old HIV-infected subject with chronic pulmonary disease had the equivalent level of function as a 68.1-year-old uninfected subject with chronic pulmonary disease. We conclude that age-associated comorbidity affects physical function in HIV-infected patients, and may modify the effect of aging. Longitudinal research with markers of disease severity is needed to investigate loss of physical function with aging, and to develop age-specific HIV care guidelines.
HCV/HIV coinfection treatment is suboptimal with low SVR rates to standard therapies. A multicenter randomized clinical trial designed to assess the efficacy/safety of pegylated-interferon maintenance therapy was performed by the NIH-funded ACTG network.
HCV treatment naïve and non-responding interferon-experienced subjects with confirmed HCV and HIV, CD4>200 cells/mm3, and at least Stage 1 fibrosis were enrolled, and treated for 12 weeks with pegylated interferon alfa 2a 180 mcg/week (PEG) + weight-based ribavirin to determine response status. Non-responder subjects (failure to clear HCV RNA or achieve 2-log drop) underwent liver biopsy and were randomized to receive full dose PEG or observation only for 72 weeks. Paired biopsies were evaluated by a central pathologist.
330 subjects were enrolled; median age was 48 years; 43% White, 37% Black, non-Hispanic; 83% male; CD4+ 498 cells/mm3; 32% were interferon experienced; 74% had entry HIV RNA<50 cp/ml. EVR was observed in 55.9% and 42.5% achieved cEVR. A planned interim analysis of occurred when 84 subjects were randomized. With data on 40 paired biopsies available, a safety monitoring board stopped the trial due to lack of fibrosis progression (median = 0 Metavir units/year) in the observation arm.
Lack of fibrotic progression in the control arm was unexpected, and may represent a short-term PEG/ribavirin therapy effect, high levels of HIV viral suppression and use of antiretroviral regimens that may be less toxic than prior generations of therapy.
HCV; HIV; Maintenance; Racial Disparity; Fibrosis
Serologic studies can provide important insights into the epidemiology and transmission of Pneumocystis jirovecii. Exposure to P. jirovecii can be assessed by serum antibody responses to recombinant antigens from the major surface glycoprotein (MsgC), although factors that influence the magnitude of the antibody response are incompletely understood. We determined the magnitudes of antibody responses to P. jirovecii in comparison to adenovirus and respiratory syncytial virus (RSV) in HIV-infected and uninfected patients and identified predictors associated with the magnitude of the response. We performed a cross-sectional analysis using serum samples and data from 153 HIV-positive and 92 HIV-negative subjects enrolled in a feasibility study of the Veterans Aging Cohort 5 Site Study (VACS 5). Antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Independent predictors of antibody responses were determined using multivariate Tobit regression models. The results showed that serum antibody responses to P. jirovecii MsgC fragments were significantly and independently decreased in current smokers. Antibodies to P. jirovecii also tended to be lower with chronic obstructive pulmonary disease (COPD), hazardous alcohol use, injection drug use, and HIV infection, although these results were not statistically significant. These results were specific to P. jirovecii and did not correlate with adenovirus. Antibody responses to RSV were in the inverse direction. Thus, current smoking was independently associated with decreased P. jirovecii antibody responses. Whether smoking exerts an immunosuppressive effect that affects the P. jirovecii antibody response, colonization, or subsequent risk for disease is unclear; prospective, longitudinal studies are needed to evaluate these findings further.
Background & Aims
Liver fibrosis is a significant concern for patients with hepatitis C virus (HCV)/HIV co-infection. Fibrosis staging by biopsy is accurate but costly and invasive. Several fibrosis prediction models utilizing non-invasive biomarkers have been developed but are suboptimal in co-infected patients. We compared results from different staging models and ordinal regression with biopsy data.
Data from the Adult AIDS Clinical Trials Group protocol A5178 were used to evaluate 5 models of fibrosis staging; areas under receiver-operator characteristic curves (AUROC) were assessed. Individual covariates were assessed with univariable regression then entered into an ordinal logistic regression model from which a stage-wise index was developed.
Data from 173 patients were evaluated; 85% were on anti-retroviral therapy, 31.2% had severe fibrosis (F3/F4) and 14% had cirrhosis (F4). Differences in CD4+ cell and platelets counts and international normalized ratio values were observed between those with and without F3/F4. Among existing models, the FIB-4 index performed best, with 88% specificity for F4 and >86% negative predictive values for F3/F4, although AUROC values were low (0.56±0.03 for F3/F4). Using patients’ demographic, clinical, and laboratory data, the ordinal regression model outperformed others, with AUROC = 0.85 (SE 0.03) for predicting stage F3/F4 and 0.89 (SE 0.05) for stage 3 alone.
Current noninvasive methods of fibrosis assessment have poor discriminatory capacity in HCV/HIV co-infected patients. Ordinal regression analysis outperformed other non-invasive fibrosis prediction models. Longitudinal studies with paired biopsies will assist in refining the ordinal regression index.
Noninvasive fibrosis assessment; HCV/HIV coinfection; Applied ordinal regression
Treatment completion rates for hepatitis C virus (HCV) infection in clinical practice settings are unknown.
We assembled a national cohort of HCV-infected veterans-in-care from 1998 to 2003, using the VA National Patient Care Database for demographical/clinical information, Pharmacy Benefits Management database for pharmacy records and the Decision Support Systems database for laboratory data. We used logistic regression to determine the factors predicting treatment non-completion for HCV.
We identified 134 934 HCV-infected veterans of whom 16 043 [11.9%; 95% confidence interval (CI) 11.7–12.1] were prescribed treatment for HCV. Among the 10 641 veterans with > 1 year of follow-up, 2396 (22.5%; 95% CI 21.7–23.3) completed a 48-week course. Non-completers were more likely to have pre-treatment anaemia, coronary artery disease, depression, substance abuse, used standard interferon, higher comorbidity count, and been treated at a low-volume treatment site (defined as sites initiating HCV treatment for < 200 individuals). In multivariable analyses, treatment completion was positively associated with pegylated interferon use [odds ratio (OR) 1.59, 95% CI 1.40–1.80] and site treatment volume (OR 1.87, 95% CI 1.56–2.24 for sites initiating treatment for > 200 individuals) and negatively associated with pre-treatment anaemia (OR 0.68, 95% CI 0.58–0.80 for haemoglobin 10–14 g/dl) and depression (OR 0.78, 95% CI 0.69–0.89). Human immunodeficiency virus coinfection and minority race were not associated with failing to complete treatment.
Among veterans-in-care with known HCV, 11.9% initiate therapy of whom 22.5% (one in 56 with known HCV infection) complete a 48-week course of treatment. Higher completion rates among higher volume treatment sites suggest that some factors associated with non-completion (pre-treatment depression and anaemia), may be modifiable with experience.
anaemia; depression; hepatitis C; HIV infection; pegylated interferon; practice variation; treatment completion
Depression is one of the most common comorbid conditions affecting persons with HIV. We compared depressive symptoms and depression treatment using data from the Veterans Aging Cohort Study (VACS), a prospective cohort of HIV-infected and uninfected subjects. We identified subjects with a Patient Health Questionnaire score of 10 or greater. Treatment was defined as prescription of a selective serotonin reuptake inhibitor (SSRI) or mental health counseling. Overall, 16% of 4,480 subjects had depressive symptoms, and HIV-infected patients were more likely to have had depressive symptoms (OR = 1.38, 95% CI = 1.18, 1.62). Geographic site of care and having a mental health provider at the clinic was associated with treatment. In multivariable models restricted to 732 patients with depressive symptoms, receipt of depression treatment did not differ by HIV status (Adjusted OR = 1.11, 95% CI = 0.80, 1.54). Non-Hispanic whites were more likely to receive treatment (Adjusted OR = 2.09, 95% CI 1.04, 4.24). Primary care and HIV providers were equally unlikely to treat active depressive symptoms. Treatment variation by race, site, and availability of a mental health provider, suggests targets for intervention.
HIV-infection; Depression; Psychiatric status rating scales; Anti-depressive agents
It is unknown whether smoking confers similar mortality risk in HIV-positive as in HIV-negative patients. We compared overall mortality stratified by HIV and smoking of 1,034 HIV-positive block-matched to 739 HIV-negative veterans, enrolled 2001–2002 in the Veterans Aging Cohort 5 Site Study. Adjusted incidence rate ratios (IRR) for mortality were calculated using Poisson regression. Mortality was significantly increased in HIV-positive veterans according to both smoking status and pack-years in unadjusted and adjusted analyses (adjusted IRR 2.31, 95% confidence interval [CI] 1.53–3.49 for HIV-positive current smokers and IRR 1.32, 95% CI 0.67–2.61 for HIV-negative current smokers). Comorbid diseases were also significantly increased according to smoking status and pack-years. Current smoking is associated with poor outcomes; even lower levels of exposure appear to be detrimental in HIV-infected veterans. These findings support the need for improvements in smoking cessation and for studies of mechanisms and diseases underlying increased mortality in smokers with HIV.
The association between hepatitis C virus (HCV) infection and coronary artery disease (CAD) is controversial. We conducted this study to determine and quantify this association.
We used an established, national, observational cohort of all HCV-infected veterans receiving care at all Veterans Affairs facilities, the Electronically Retrieved Cohort of HCV Infected Veterans, to identify HCV-infected subjects and HCV-uninfected control subjects. We used the Cox proportional-hazards model to determine the risk of CAD among HCV-infected subjects and control subjects.
We identified 82,083 HCV-infected and 89,582 HCV-uninfected subjects. HCV-infected subjects were less likely to have hypertension, hyperlipidemia, and diabetes but were more likely to abuse alcohol and drugs and to have renal failure and anemia. HCV-infected subjects had lower mean (± standard deviation) total plasma cholesterol (175 ± 40.8 mg/dL vs. 198 ± 41.0 mg/dL), low-density lipoprotein cholesterol (102 ± 36.8 mg/dL vs. 119 ± 38.2 mg/dL), and triglyceride (144 ± 119 mg/dL vs. 179 ± 151 mg/dL) levels, compared with HCV-uninfected subjects. In multivariable analysis, HCV infection was associated with a higher risk of CAD (hazard ratio, 1.25; 95% confidence interval, 1.20–1.30; P < .001 for all comparisons). Traditional risk factors (age, hypertension, chronic obstructive pulmonary disease, diabetes, and hyperlipidemia) were associated with a higher risk of CAD in both groups, whereas minority race and female sex were associated with a lower risk of CAD.
HCV-infected persons are younger and have lower lipid levels and a lower prevalence of hypertension. Despite a favorable risk profile, HCV infection is associated with a higher risk of CAD after adjustment for traditional risk factors.
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.
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.
We undertook a prospectively consented multisite observational study of veterans in care with and without HIV infection.
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.
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.
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.
HIV/AIDS; alcohol; aging veterans; data management/research design
Approximately 3.2 million people in the United States have chronic hepatitis C virus (HCV) infection; the primary cause for adult liver transplantation and a significant burden on healthcare resources. The role of HCV and other risk factors in development of HCC in patients with chronic kidney disease is not well defined.
To identify specific predictors of hepatocellular carcinoma (HCC) in dialysis patients with chronic HCV.
This study assessed factors associated with the development of HCC in dialysis patients with chronic HCV. Data were extracted from the United States Renal Database System (USRDS) using ICD-9 codes. Variables included were gender, race, duration on dialysis, and comorbidities (alcohol abuse, drug abuse, HIV, hepatitis B, diabetes and/or presence of cirrhosis).
Among the 32,806 HCV infected subjects, 262 cases had HCC. HCC was 12 times more likely in subjects with cirrhosis (p<.001), 3 times more likely in subjects with alcohol abuse (p<.001), and 1.3 times more likely in subjects with diabetes (p=.04). Asians were 3 times more likely (p<.001) to have HCC. Females were less likely to have HCC compared to males (p=.002). The likelihood of having HCC increased with age (p=.001).
This population-based study demonstrates that among subjects with HCV on dialysis, those with cirrhosis, Asian race and history of alcohol abuse are at highest risk for development of HCC. Furthermore, these findings indicate links between HCV and HCC which are valuable in case management for identifying; monitoring, and managing dialysis patients with HCC.
hepatitis C; hepatocellular carcinoma; dialysis; co-morbidity; end stage renal disease
Treatment rates for hepatitis C virus (HCV) have not been compared directly between HCV mono-infected and HCV–HIV co-infected patients in academic center settings.
We prospectively enrolled consecutive mono-infected and co-infected subjects at three academic centers in the USA. Clinical and laboratory data were gathered through interviews and medical records. Logistic regression analysis was used to determine the factors associated with treatment prescription for HCV.
The 241 HCV mono-infected and 158 HCV–HIV co-infected subjects were similar in age, but there were more blacks (58.9% vs. 30.7%, p < 0.001) and males (81.6% vs. 58.5%, p < 0.001) in the latter group. The co-infected subjects were less likely to have a liver biopsy (43.7% vs. 71.4%, p < 0.001) or ever receive treatment for HCV (32.3% vs. 62.2%, p < 0.001). In bivariate analysis, subjects not prescribed treatment for HCV were more likely to be black, have HIV co-infection, and have ongoing alcohol abuse. In multivariate analysis, black race (odds ratio (OR) 0.44, 95% confidence interval (CI) 0.28–0.70) and HIV co-infection (OR 0.33, 95% CI 0.21–0.53) were independently associated with non-prescription of treatment.
Black race and HIV co-infection are associated with a lower likelihood of treatment for HCV. Addressing comorbidities in these populations may help to reduce such treatment disparities.
Hepatitis C virus; HIV; Co-infection; Treatment rates; Racial disparity
The influence of HIV infection on the risk of diabetes is unclear. We determined the association and predictors of prevalent DM in HIV infected and uninfected veterans.
We determined baseline prevalence and risk factors for diabetes among HIV infected and uninfected veterans in the Veterans Aging Cohort Study. Logistic regression was used to determine the odds of diabetes in HIV infected and uninfected persons.
We studied 3,327 HIV-infected and 3,240 HIV-uninfected subjects. HIV infected subjects were younger, more likely to be black race, male, have HCV coinfection and a lower body mass index (BMI). HIV infected subjects had a lower prevalence of diabetes at baseline (14.9% vs. 21.4%, P<0.0001). After adjustment for known risk factors, HIV infected individuals had a lower risk of diabetes (OR 0.84, 95% CI 0.72-0.97). Increasing age, male gender, minority race, and BMI were associated with an increased risk. The odds ratio for diabetes associated with increasing age, minority race and BMI were greater among HIV infected veterans. HCV coinfection and nucleoside and non-nucleoside reverse transcriptase inhibitor therapy were associated with a higher risk of diabetes in HIV infected veterans.
While HIV infection itself is not associated with increased risk of diabetes, increasing age, HCV coinfection and BMI have a more profound effect upon the risk of diabetes among HIV infected persons. Further, long term ARV treatment also increases risk. Future studies will need to determine whether incidence of DM differs by HIV status.
HIV; diabetes; HCV; risk; antiretroviral therapy
Treatment eligibility rates in patients with HCV monoinfection have not been directly compared with patients with HCV/HIV coinfection. These data are important for planning interventions to optimize HCV management.
We enrolled consecutive HCV-monoinfected and HCV/HIV-coinfected subjects presenting to hepatology and HIV clinics at three academic medical centers. Data were obtained through structured subject and provider interviews and a review of medical records.
Of the 399 subjects enrolled, 241 (60%) were HCV monoinfected and 158 (40%) were HCV/HIV coinfected. HCV/HIV-coinfected subjects were less likely to have indications for treatment based on HCV RNA positivity (70.9% vs. 81.3%, p = .04) but were more likely to have at least one contraindication to treatment (81.6% vs. 64.9%, p < .004). Depression and ongoing alcohol and injection drug abuse were more common in the HCV/HIV-coinfected persons. HCV/HIV coinfected persons were less likely to undergo liver biopsy or to ever get treatment for HCV.
HCV/HIV-coinfected persons are less likely to undergo a liver biopsy or be eligible for HCV therapy and are more likely to have treatment contraindications compared with HCV-monoinfected subjects. Strategies to address modifiable factors (e.g., depression, substance abuse) may enhance treatment eligibility in HCV-infected populations.
To examine the association between HIV infection status and the receipt of lipid lowering therapy based on National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) guidelines and to assess whether HIV viral load and hepatitis C (HCV) status alters that association.
PARTICIPANTS AND DESIGN
A cross-sectional analysis of survey, laboratory, and pharmacy data from 1,577 male participants (59% HIV infected) of the Veterans Aging Cohort Five-Site Study, a prospective observational cohort of U.S. veterans with and without HIV infection.
Receipt of lipid lowering therapy obtained from the VA pharmacy benefits management system was the main outcome.
The prevalence of lipid lowering therapy among HIV-infected and HIV-uninfected veterans was 15.4% vs. 37.9%, respectively, < 0.01. Among veterans who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans had a significantly lower prevalence for the receipt of lipid lowering therapy (adjusted odds ratio (OR) = 0.43, 95% confidence interval (C.I.) 0.28–0.67) as compared with HIV-uninfected veterans. Among HIV-infected veterans, log HIV viral load (adjusted OR = 0.57, 95% CI, 0.41–0.81) and HIV-HCV co-infection (adjusted OR = 0.31, 95% CI = 0.13–0.75) were negatively associated with receipt of lipid lowering therapy. Exposure to HAART was not associated with receipt of lipid lowering therapy.
Among those who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans, particularly those with high HIV viral loads and HCV co-infection, were significantly less likely to receive lipid lowering therapy. This may be a modifiable mediator of cardiovascular disease among HIV-infected individuals.
HIV; cholesterol; hepatitis C; men; veterans; cardiovascular diseases
The true treatment rate for hepatitis C virus (HCV) in veterans is unknown.
To determine the treatment prescription rates and predictors of treatment prescription for HCV in a large national population.
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.
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).
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.
Cigarette smoking is an important risk factor for morbidity and mortality in HIV-positive patients on combination antiretroviral therapy.
To determine whether awareness of smoking differs between HIV and non-HIV providers, and to identify factors associated with failure to recognize current smoking.
801 HIV-positive and 602 HIV-negative patients, 72 HIV and 71 non-HIV providers enrolled in the Veterans Aging Cohort 5 Site Study.
Data sources included patient and provider questionnaires; electronic medical records; and the national administrative VA database. We calculated sensitivity, specificity, and measures of agreement between patient- and provider-reported smoking, and examined factors associated with failure to recognize current smoking using logistic regression.
Whereas most providers were correct when they identified a patient as a current smoker (specificity ≥90%), HIV providers missed current smoking more often (sensitivity 65% for HIV vs. 82% for non-HIV). Kappa scores for current smoking were significantly lower for HIV compared to non-HIV providers (0.55 vs. 0.75, p < .001). In models adjusted for age, gender, race, and other differences, patient HIV status and provider specialty in infectious diseases were independent predictors of a provider’s failure to recognize current smoking. Comorbid illnesses, cough/dyspnea, degree of immune competence and HIV viral suppression did not impact recognition of current smoking. Only 39% of HIV providers reported confidence in their ability to influence smoking cessation compared to 62% of non-HIV providers (p = .049).
Interventions to increase HIV provider awareness of current smoking and skills to influence smoking cessation are needed. Efforts should also target patient populations with smoking-related comorbid diseases who would especially benefit from smoking cessation.
tobacco; detection of smoking; HIV; smoking cessation
The impact of smoking on outcomes among those with HIV infection has not been determined in the era of highly active antiretroviral therapy (HAART).
Determine the impact of smoking on morbidity and mortality in HIV-positive patients post-HAART.
Prospective observational study.
Eight hundred and sixty-seven HIV-positive veterans enrolled in the Veterans Aging Cohort 3 Site Study.
Clinical data were collected through patient questionnaire, International Classification of Diseases—9th edition codes, and standardized chart extraction, and laboratory and mortality data through the national VA database. Quality of life was assessed with the physical component summary (PCS) of the Short-Form 12.
Current smokers had increased respiratory symptoms, chronic obstructive pulmonary disease (COPD), and bacterial pneumonia. In analyses adjusted for age, race/ethnicity, CD4 cell count, HIV RNA level, hemoglobin, illegal drug and alcohol use, quality of life was substantially decreased (β=−3.3, 95% confidence interval [CI] −5.3 to −1.4) and mortality was significantly increased (hazard ratio 1.99, 95% CI 1.03 to 3.86) in current smokers compared with never smokers.
HIV-positive patients who currently smoke have increased mortality and decreased quality of life, as well as increased respiratory symptoms, COPD, and bacterial pneumonia. These findings suggest that smoking cessation should be emphasized for HIV-infected patients.
HIV; AIDS; smoking; mortality; health-related quality of life