Kendall Bryant

HIV Infection and the Risk of Acute Myocardial Infarction

IMPORTANCE Whether people infected with human immunodeficiency virus (HIV) are at an increased risk of acute myocardial infarction (AMI) compared with uninfected people is not clear. Without demographically and behaviorally similar uninfected comparators and without uniformly measured clinical data on risk factors and fatal and nonfatal AMI events, any potential association between HIV status and AMI may be confounded. OBJECTIVE To investigate whether HIV is associated with an increased risk of AMI after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar (ie, similar prevalence of smoking, alcohol, and cocaine use) uninfected veterans in care. DESIGN AND SETTING Participants in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009. PARTICIPANTS After eliminating those with baseline cardiovascular disease, we analyzed data on HIV status, age, sex, race/ethnicity, hypertension, diabetes mellitus, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV-1 RNA, antiretroviral therapy, and incidence of AMI. MAIN OUTCOME MEASURE Acute myocardial infarction. RESULTS We analyzed data on 82 459 participants. During a median follow-up of 5.9 years, there were 871 AMI events. Across 3 decades of age, the mean (95% CI) AMI events per 1000 person-years was consistently and significantly higher for HIV-positive compared with uninfected veterans: for those aged 40 to 49 years, 2.0 (1.6-2.4) vs 1.5 (1.3-1.7); for those aged 50 to 59 years, 3.9 (3.3-4.5) vs 2.2 (1.9-2.5); and for those aged 60 to 69 years, 5.0 (3.8-6.7) vs 3.3 (2.6-4.2) (P < .05 for all). After adjusting for Framingham risk factors, comorbidities, and substance use, HIV-positive veterans had an increased risk of incident AMI compared with uninfected veterans (hazard ratio, 1.48; 95% CI, 1.27-1.72). An excess risk remained among those achieving an HIV-1 RNA level less than 500 copies/mL compared with uninfected veterans in time-updated analyses (hazard ratio, 1.39; 95% CI, 1.17-1.66). CONCLUSIONS AND RELEVANCE Infection with HIV is associated with a 50% increased risk of AMI beyond that explained by recognized risk factors.

One-year follow-up status of treatment-seeking cocaine abusers. Psychopathology and dependence severity as predictors of outcome.

While the prognostic significance of eomorbid psychopathology and dependence severity has been demonstrated with opiate addicts and alcoholics, no previous reports have examined those issues in cocaine abusers. We reinterviewed 94 cocaine abusers 1 year after they sought treatment to assess predictors of treatment retention and outcome. Results suggested that: a) Many cocaine abusers did comparatively well; fully a third reported complete abstinence during the 12 months preceding the follow-up interview. b) Throe variables emerged as consistent predictors across several outcome domains: severity of drug use, poorer psychiatric functioning, and presence of concurrent alcoholism. c) The data supported a unidimensional model of outcome for cocaine abuse that emphasized reduction in level of substance use. However, abstinence was not strongly associated with improved functioning in all outcome areas. d) Variables associated with longer retention in treatment also tended to predict poorer outcome.

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.

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.

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

Background:The VAs 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 VAs 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.

HIV status, burden of comorbid disease, and biomarkers of inflammation, altered coagulation, and monocyte activation

BACKGROUND Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)-infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS). METHODS Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (d-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities. RESULTS HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA ≥500 copies/mL or CD4 count <200 cells/µL had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI],1.14-2.09; OR, 2.25; 95% CI, 1.60-3.16, respectively) and d-dimer (OR, 1.97; 95% CI, 1.44-2.71, OR, 1.68; 95% CI, 1.22-2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/µL had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64-4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions. CONCLUSIONS These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid 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 ≥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 ≥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.

Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers

As those with HIV infection live longer, ‘non‐AIDS’ condition associated with immunodeficiency and chronic inflammation are more common. We ask whether ‘non‐HIV’ biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART).

Does an Index Composed of Clinical Data Reflect Effects of Inflammation, Coagulation, and Monocyte Activation on Mortality Among Those Aging With HIV?

BACKGROUND When added to age, CD4 count and human immunodeficiency virus type 1 (HIV-1) RNA alone (Restricted Index), hemoglobin, FIB-4 Index, hepatitis C virus (HCV), and estimated glomerular filtration rate improve prediction of mortality. Weighted and combined, these 7 routine clinical variables constitute the Veterans Aging Cohort Study (VACS) Index. Because nonroutine biomarkers of inflammation (interleukin 6 [IL-6]), coagulation (D-dimer), and monocyte activation (sCD14) also predict mortality, we test the association of these indices and biomarkers with each other and with mortality. METHODS Samples from 1302 HIV-infected veterans on antiretroviral therapy were analyzed. Indices were calculated closest to date of collection. We calculated Spearman correlations stratified by HIV-1 RNA and HCV status and measured association with mortality using C statistics and net reclassification improvement (NRI). RESULTS Of 1302 subjects, 915 had HIV-1 RNA <500 copies/mL and 154 died. The VACS Index was more correlated with IL-6, D-dimer, and sCD14 than the Restricted Index (P < .001). It was also more predictive of mortality (C statistic, 0.76; 95% confidence interval [CI], .72-.80) than any biomarker (C statistic, 0.66-0.70) or the Restricted Index (C statistic, 0.71; 95% CI, .67-.75). Compared to the Restricted Index alone, NRI resulted from incremental addition of VACS Index components (10%), D-dimer (7%), and sCD14 (4%), but not from IL-6 (0%). CONCLUSIONS Among HIV-infected individuals, independent of CD4, HIV-1 RNA, and age, hemoglobin and markers of liver and renal injury are associated with inflammation. Addition of D-dimer and sCD14, but not IL-6, improves the predictive accuracy of the VACS Index for mortality.

Expanding Research on the Role of Alcohol Consumption and Related Risks in the Prevention and Treatment of HIV/AIDS

This article is a review of some of the major epidemiological, behavioral, biological, and integrative prevention research issues and priorities in the area of HIV_AIDS and alcohol consumption. Drinking alcohol increases both the risk for infection with HIV and related illnesses and the morbidity and mortality of patients who progress to AIDS. New and improved measurement procedures have helped in assessment of the complex patterns of alcohol use, identification of intervening explanatory mechanisms for risk behaviors and contexts, and determination of intervention outcomes. Both the direct and indirect effects of alcohol misuse appear to be major contributors to both the risk for infection with HIV and the transmission of HIV_AIDS at the individual and population levels. There is increasing evidence that perhaps no level of alcohol consumption is “safe” for those who are HIV infected and receiving antiretroviral treatment. Interdisciplinary basic behavioral and biomedical research is needed to develop comprehensive culturally appropriate strategies for programs that can be effectively delivered in community contexts in the United States and abroad and that focus on the integration of our understanding of individual behaviors, high-risk group membership, biological mechanisms, and the social and physical environments that place individuals at risk for HIV infection. High-priority topics include improving adherence to antiretroviral medications, prevention of infection in young minority women in the United States, and treatment of HIV+ pregnant women who are alcohol abusers to prevent adverse fetal outcomes, which is an international focus in under-resourced settings in Africa.