Faculty Bibliography

Background 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). Methods Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV-infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS-defining conditions); 'non-HIV' biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data. Results Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle-aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and 'non-HIV' markers were associated with each other (P<0.0001) and discriminated mortality (C statistics 0.68-0.73); when combined, discrimination improved (P<0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30-day C statistic 0.86, 95% confidence interval (CI) 0.80-0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72-0.74). Results were robust to adjustment for missing data. Conclusions When added to HIV biomarkers, 'non-HIV' biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research

BACKGROUND: Health care providers may be concerned that prescribing erectile dysfunction drugs (EDD) will contribute to risky sexual behavior. OBJECTIVES: To identify characteristics of men who received EDD prescriptions, determine whether EDD receipt is associated with risky sexual behavior and sexually transmitted diseases (STDs), and determine whether these relationships vary for certain sub-groups. DESIGN: Cross-sectional study. PARTICIPANTS: Two thousand seven hundred and eighty-seven sexually-active, HIV-infected and HIV-uninfected men recruited from eight Veterans Health Affairs outpatient clinics. Data were obtained from participant surveys, electronic medical records, and administrative pharmacy data. MEASURES: EDD receipt was defined as two or more prescriptions for an EDD, risky sex as having unprotected sex with a partner of serodiscordant or unknown HIV status, and STDs, according to self-report. RESULTS: Overall, 28% of men received EDD in the previous year. Eleven percent of men reported unprotected sex with a serodiscordant/unknown partner in the past year (HIV-infected 15%, HIV-uninfected 6%, P < 0.001). Compared to men who did not receive EDD, men who received EDD were equally likely to report risky sexual behavior (11% vs. 10%, p = 0.9) and STDs (7% vs 7%, p = 0.7). In multivariate analyses, EDD receipt was not significantly associated with risky sexual behavior or STDs in the entire sample or in subgroups of substance users or men who had sex with men. CONCLUSION: EDD receipt was common but not associated with risky sexual behavior or STDs in this sample of HIV-infected and uninfected men. However, risky sexual behaviors persist in a minority of HIV-infected men, indicating ongoing need for prevention interventions

Antiretroviral therapy (ART) has substantially altered the fate of HIV-infected people, transforming the infection from an invariably fatal disease to a chronic condition manageable by pharmacotherapy. However, in order for ART to be effective, patients must adhere strictly to an often-demanding treatment regimen. Alcohol consumption may impact survival of HIV-infected patients through a variety of pathways. Some of these are not related to the effectiveness of ART (e.g., alcohol-induced immunosuppression that exacerbates the HIV-related immunosuppression, increased hepatotoxicity, and increased mortality from non-HIV-related causes). However, some pathways mediating alcohol's negative effect on survival are related to ART effectiveness. In particular, alcohol consumption may reduce adherence to ART, leading to decreased ART effectiveness and, ultimately, increased HIV-related mortality. Both clinical data and computer simulations have yielded information about the impact of alcohol consumption on medication adherence in both HIV-infected and noninfected patients. The findings suggest that alcohol-related nonadherence may account for a substantial amount of preventable mortality among HIV-infected patients. These findings may have clinical implications with respect to optimal treatment for HIV-infected patients who also consume alcohol.

Many people at risk for or already infected with HIV abuse alcohol, contributing to the difficulties in preventing the spread of the infection and treating infected patients. Thus, alcohol-abusing patients may delay testing for HIV, accessing appropriate medical care, and initiating antiretroviral therapy (ART), which may hasten disease progression to full-blown AIDS. Alcohol abuse also increases the risk of HIV infection by promoting risky behaviors and counteracting efforts to minimize the risk of infection, prevent transmission of the virus to others once exposure has occurred, and reduce the risk of progression and organ or tissue injury after infection. In HIV-infected people undergoing treatment, concurrent alcohol abuse often renders treatment ineffective because patients frequently fail to adhere to the strict treatment regimens necessary to achieve control of the infection. Moreover, alcohol may interact with ART medications and exacerbate adverse effects of these medications. Future research needs to better integrate behavioral and biological research to identify strategies to prevent the spread of HIV infection in alcohol-abusing populations as well as focus on translational research to effectively implement promising approaches on a large scale.

BACKGROUND: Practice guidelines rarely consider comorbid illness, and resulting overuse of health services may increase costs without conferring benefit. OBJECTIVE: To individualize a framework for inferring when patients with comorbid illness are not likely to benefit from colorectal cancer screening guidelines. METHODS: We modified the 'payoff time' framework (the minimum time until a guideline's cumulative benefits exceed its cumulative harms) to increase its applicability to a wide range of primary care patients. We show how it may inform colorectal (CR) cancer screening decisions for 3 typical patients in general practice for whom CR screening would be recommended by current guidelines: (1) 60-year-old man with diabetes, congestive heart failure, lung disease, stroke, and substantial frailty; (2) 60-year-old woman with diabetes and obesity, without other comorbidity or frailty; and (3) 50-year-old woman with inflammatory bowel disease. RESULTS: For patient 1, the payoff time for CR screening (minimum time until benefits exceed harms) is 7.3 years, and for patient 2, the payoff time for CR screening is 5.4 years. Evidence is insufficient to estimate the payoff time for patient 3. Because patient 1's estimated life expectancy is 3.7 years (less than his payoff time), he is unlikely to benefit from CR screening. Because patient 2's estimated life expectancy exceeds 10 years (greater than her payoff time), she may benefit from CR screening. Because evidence is insufficient to estimate the payoff time for patient 3, the payoff time framework does not inform decision making. CONCLUSION: The payoff time framework may identify patients for whom particular clinical guidelines are unlikely to confer benefit, and has the potential to decrease unnecessary health care

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

Clinicians may defer antiretroviral treatment for patients with suboptimal adherence. We used a validated computer simulation of HIV disease progression to compare alternative treatment thresholds for patients with suboptimal adherence. Earlier treatment increased life expectancy across a wide adherence range (50%-100% of doses taken). Delaying treatment for patients with suboptimal adherence may not always be appropriate

This randomized clinical trial replicated the efficacy of the ePREP preventive intervention for mental health and relationship relevant outcomes in a sample of 77 college students. It extended previous research by demonstrating efficacy at a 10-month follow up. Participants in the ePREP condition experienced improved mental health and relationship relevant outcomes relative to those who received a placebo intervention. The impact of the ePREP intervention on these outcomes was durable to relationship dissolution with and without repartnering. The flexibility of this intervention empowers it to overcome key obstacles in the dissemination of relationship education

The mechanisms through which current romantic relationship dysfunction develops in individuals with borderline personality disorder (BPD) symptoms are still unclear. One possible pathway may be childhood experiences of emotional invalidation by parents, which may result in the development of poor social problem-solving skills or cognitive responses such as splitting, which impair current romantic relationships. This study examines the relationship between features of BPD and current romantic relationship dysfunction, and demonstrates that perceived emotional invalidation by parents during childhood mediates the relationship between BPD features and current romantic relationship dysfunction. Structural equations modeling was used to test the hypothesized model in 758 young adults in an ethnically diverse community sample. The proposed model fit the data well; perceived childhood emotional invalidation partially mediated the relationship between features of BPD and romantic relationship dysfunction, even when controlling for the presence of a major depressive episode in the last year. The findings of this study suggest that individuals with features of BPD experience relationship dysfunction that cannot be accounted for by comorbid depression and that perceived childhood emotional invalidation may contribute to these problems

BACKGROUND: Screening for hazardous drinking may fail to detect a substantial proportion of individuals harmed by alcohol. We investigated whether considering an individual's usual drinking quantity or threshold for alcohol-induced cognitive impairment improves the prediction of nonadherence with prescribed medications. METHOD: Cross-sectional analysis of participants in a large, multi-site cohort study. We used the timeline followback to reconstruct 30-day retrospective drinking histories and the timeline followback modified for adherence to reconstruct 30-day medication adherence histories among 3,152 individuals in the Veterans Aging Cohort Study, 1,529 HIV infected and 1,623 uninfected controls. We categorized daily alcohol consumption by using quantity alone, quantity after adjustment for the individual's mean daily alcohol consumption, and self-reported level of impairment corresponding to each quantity. A standard drink was defined as 14 g of ethanol. Nonadherence was defined as the proportion of days with > or =1 medication doses missed or taken > or =2 hours late, and clinically significant nonadherence was defined as > or =5% absolute increase in the proportion of days with nonadherence. RESULTS: The mean adjusted- and impairment-based methods showed greater discrimination of nonadherence risk compared to the measure based on quantity alone (quantity-based categorization, 3.2-fold increase; quantity adjusted for mean daily consumption, 4.6-fold increase, impairment-based categorization, 3.6-fold increase). The individualized methods also detected greater numbers of days with clinically significant nonadherence associated with alcohol. Alcohol was associated with clinically significant nonadherence at a lower threshold for HIV infected versus uninfected patients (2 standard drinks vs. 4 standard drinks) using quantity-based categorization, but this difference was no longer apparent when individualized methods were used. CONCLUSIONS: Tailoring screening questions to an individual's usual level of alcohol consumption or threshold for impairment improves the ability to predict alcohol-associated medication nonadherence