Kathleen A. McGinnis

The Impact of Cigarette Smoking on Mortality, Quality of Life, and Comorbid Illness Among HIV‐Positive Veterans

AbstractBACKGROUND: The impact of smoking on outcomes among those with HIV infection has not been determined in the era of highly active antiretroviral therapy (HAART). STUDY OBJECTIVE: Determine the impact of smoking on morbidity and mortality in HIV-positive patients post-HAART. DESIGN: Prospective observational study. PARTICIPANTS: Eight hundred and sixty-seven HIV-positive veterans enrolled in the Veterans Aging Cohort 3 Site Study. MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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 infection and the risk of diabetes mellitus.

Background:The influence of HIV infection on the risk of diabetes is unclear. We determined the association and predictors of prevalent diabetes mellitus in HIV infected and uninfected veterans. Methods:We determined baseline prevalence and risk factors for diabetes between 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. Results:We studied 3227 HIV-infected and 3240 HIV-uninfected individuals. HIV-infected individuals were younger, more likely to be black males, have HCV coinfection and a lower BMI. HIV-infected individuals 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 (odds ratio = 0.84, 95% confidence interval = 0.72–0.97). Increasing age, male sex, 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 nonnucleoside reverse transcriptase inhibitor therapy were associated with a higher risk of diabetes in HIV-infected veterans. Conclusion:Although 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 diabetes mellitus differs by HIV status.

A temporal and dose-response association between alcohol consumption and medication adherence among veterans in care.

BACKGROUND Previous studies have shown that alcohol consumption is associated with decreased medication adherence, but this association may be confounded by characteristics common among those who drink heavily and those who fail to adhere (e.g., illicit drug use). Our objective was to determine whether there are temporal and dose-response relationships between alcohol consumption and poor adherence. METHODS We administered telephone interview surveys to participants in the Veterans Aging Cohort Study, an eight-site observational study of HIV+ and matched HIV- veterans in care, to determine whether alcohol consumption on a particular day was associated with nonadherence to prescribed medications on that same day. We used the Time Line Follow Back to measure alcohol consumption and the Time Line Follow Back Modified for Adherence to measure adherence. Individuals were categorized as abstainers (no alcohol in past 30 days), nonbinge drinkers (alcohol in past 30 days but < or =four standard drinks on each day), or binge drinkers (> or =five standard drinks on at least one day). RESULTS Among 2702 respondents, 1582 (56.6%) were abstainers, 931 (34.5%) were nonbinge drinkers, and 239 (8.9%) were binge drinkers. Abstainers missed medication doses on 2.4% of surveyed days. Nonbinge drinkers missed doses on 3.5% of drinking days, 3.1% of postdrinking days, and 2.1% of nondrinking days (p < 0.001 for trend), and this trend was more pronounced among HIV+ individuals than HIV- individuals. Binge drinkers missed doses on 11.0% of drinking days, 7.0% of postdrinking days, and 4.1% of nondrinking days (p < 0.001 for trend), and this trend was comparably strong for HIV+ and HIV- individuals. CONCLUSIONS Among veterans in care, self-reported alcohol consumption demonstrates a temporal and dose-response relationship to poor adherence. HIV+ individuals may be particularly sensitive to alcohol consumption.

Incidence of Non-AIDS-Defining Malignancies in HIV-Infected Versus Noninfected Patients in the HAART Era: impact of Immunosuppression

Background:The incidence of non-AIDS-defining malignancies (non-ADMs) is reported as unchanged or increasing in the highly active antiretroviral therapy era. Whether incidence of non-ADM is significantly higher in HIV-infected than in HIV-uninfected patients remains unclear. Methods:Incidence rates of malignancies were calculated in a cohort of veterans in care for HIV-infected and age, race, and gender-matched uninfected patients from 1997 to 2004. For HIV-infected patients, CD4 counts closest to first observation date were compared between those with and without cancer. Results:Thirty three thousand four hundred twenty HIV-infected and 66,840 HIV-uninfected patients were followed for a median of 5.1 and 6.4 years. The incidence rate ratio of HIV infected to HIV uninfected was 1.6 (1260 vs. 841 per 100,000 person-years; 95% confidence interval: 1.5 to 1.7). Incidence rate ratio for individual cancers was highest for anal cancer (14.9; confidence interval: 10.1 to 22.1). Among HIV-infected patients, median CD4 counts were lower for those with non-ADM (249 vs. 270, P = 0.02), anal cancer (156 vs. 270; P < 0.001), and Hodgkin lymphoma (217 vs. 269; P = 0.03). Prostate cancer was associated with a higher CD4 count (311 vs. 266; P < 0.001). Conclusions:In the highly active antiretroviral therapy era, the incidence of non-ADMs is higher among HIV-infected than HIV-uninfected patients, adjusting for age, race, and gender. Some non-ADMs do not seem to be associated with significantly lower CD4 counts.

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).

Psychiatric and neurocognitive disorders among HIV-positive and negative veterans in care: Veterans Aging Cohort five-site Study

Background: The risk for psychiatric and neurocognitive disorders among middle-aged and older individuals with HIV infection has not been well characterized. Methods: The Veterans Aging Cohort 5-Site Study enrolled 1803 patients (1047 HIV-positive) from VA infectious disease and general medicine clinics from September 2001 to June 2002. A convenience subset of 10 patients from each site (n = 50) was consented for formal neurocognitive and psychiatric (NCP) testing. Data from this subset were linked to the larger sample. Results: Kappa scores for agreement beyond chance were fair for available measures when compared with formal NCP testing. Using available measures, depressive symptoms (PHQ-9 and provider reported), alcohol abuse or dependence (ICD-9 codes), and drug abuse or dependence (DAST-10) decreased with age in HIV-negative subjects (P trend <0.05) but did not among HIV-positive subjects (P > 0.05). HIV-positive subjects demonstrated higher prevalence of these conditions with increasing age when compared to HIV-negative subjects. Patient report of memory problems increased with age among both groups after excluding those reporting symptoms of depression (PHQ-9e ⩾ 10). Conclusion: Available measures were no substitute for formal NCP testing. Older HIV-positive veterans demonstrate greater prevalence of depressive symptoms, alcohol abuse or dependence, and drug abuse or dependence than age-matched, HIV-negative veterans. Both groups reported increased memory problems with advancing age. This preliminary work suggests a substantial prevalence of psychiatric and neurocognitive problems among middle-aged and older HIV-infected individuals.

Clinical Importance of HIV and Depressive Symptoms Among Veterans with HIV Infection

OBJECTIVE: To compare the clinical importance (association with illness severity and survival) of depressive and HIV symptoms among veterans with HIV infection.DESIGN: Cross-sectional study; survival analysis.SETTING: Infectious Disease Clinics at 3 VA Medical Centers.PARTICIPANTS: HIV-infected patients (N=881) and their health care providers from June 1999 through July 2000.MEASUREMENTS AND MAIN RESULTS: Depressive symptoms were assessed using the 10-item Centers for Epidemiologic Studies Depression Scale (CES-D). Patient baseline survey included an HIV Symptom Index measuring the frequency and bother of 20 common symptoms. Providers were surveyed on patients’ illness severity, and survival data were obtained from VA death records. Of 881 patients, 46% had significant depressive symptoms (CES-D ≥10). Increasing depression symptom severity was associated with increasing HIV symptom frequency (P<.001) and bother (P<.001). Multiple regression results revealed that having moderate or severe depressive symptoms was not associated with provider-reported illness severity or survival. However, HIV symptoms were significantly associated with provider-reported illness severity (P<.01) and survival (P=.05), after adjusting for moderate and severe depressive symptoms, CD4 cell count/mm3, viral load, age, race, and antiretroviral use.CONCLUSIONS: Depression, while common in this sample, was not associated with illness severity or mortality after adjusting for HIV symptoms. HIV symptoms are associated with severity of illness and survival regardless of patients’ severity of depressive symptoms. This suggests that equal medical consideration should be given to HIV symptoms presented by HIV-infected patients regardless of their depression status, rather than automatically attributing medical complaints to depression.

Comparison of Risk and Age at Diagnosis of Myocardial Infarction, End-Stage Renal Disease, and Non-AIDS-Defining Cancer in HIV-Infected Versus Uninfected Adults

BACKGROUND Although it has been shown that human immunodeficiency virus (HIV)-infected adults are at greater risk for aging-associated events, it remains unclear as to whether these events happen at similar, or younger ages, in HIV-infected compared with uninfected adults. The objective of this study was to compare the median age at, and risk of, incident diagnosis of 3 age-associated diseases in HIV-infected and demographically similar uninfected adults. METHODS The study was nested in the clinical prospective Veterans Aging Cohort Study of HIV-infected and demographically matched uninfected veterans, from 1 April 2003 to 31 December 2010. The outcomes were validated diagnoses of myocardial infarction (MI), end-stage renal disease (ESRD), and non-AIDS-defining cancer (NADC). Differences in mean age at, and risk of, diagnosis by HIV status were estimated using multivariate linear regression models and Cox proportional hazards models, respectively. RESULTS A total of 98 687 (31% HIV-infected and 69% uninfected) adults contributed >450 000 person-years and 689 MI, 1135 ESRD, and 4179 NADC incident diagnoses. Mean age at MI (adjusted mean difference, -0.11; 95% confidence interval [CI], -.59 to .37 years) and NADC (adjusted mean difference, -0.10 [95% CI, -.30 to .10] years) did not differ by HIV status. HIV-infected adults were diagnosed with ESRD at an average age of 5.5 months younger than uninfected adults (adjusted mean difference, -0.46 [95% CI, -.86 to -.07] years). HIV-infected adults had a greater risk of all 3 outcomes compared with uninfected adults after accounting for important confounders. CONCLUSIONS HIV-infected adults had a higher risk of these age-associated events, but they occurred at similar ages than those without HIV.