Faculty Bibliography

Objective: Uncertainty about the value of antiretroviral therapy (ARV) adherence interventions may be a barrier to implementation and evaluation. Our objective is to estimate the minimum effectiveness required for ARV adherence interventions to deliver acceptable value. Methods: We used a validated HIV computer simulation to estimate the impact of ARV adherence interventions on incremental costs and life expectancy. Across a wide range of intervention costs ($1000-10,000, one time or per year), we estimated the smallest effect size compatible with acceptable value (incremental cost-effective ratio </=$100,000 per life-year). Effect sizes were measured using relative risk (RR) and absolute risk reduction (ARR), and these metrics were applied to nonadherence and nonadherence risk factors. Costs were estimated from a societal perspective ($2003) discounted at 3%. Results: To give acceptable value, a one-time $1000 intervention must reduce ARV nonadherence by RR </= 0.82 (ARR >/= 0.04) for moderately nonadherent patients (20% of ARV doses missed) and RR </= 0.90 (ARR >/= 0.05) for severely nonadherent patients (50% of ARV doses missed). A one-time $5000 intervention has an unacceptable value regardless of effect size for moderately nonadherent patients, and must reduce ARV nonadherence by RR </= 0.31 (ARR >/= 0.69) for severely nonadherent patients. Interventions aimed at behavioral risk factors (e.g., unhealthy alcohol use) may confer acceptable value (e.g., if </=$2000 and effect RR </= 0.71 [ARR >/= 0.29]). Conclusions: ARV adherence interventions with plausible effect sizes may offer favorable value if they cost <$5000 one time or per year. ARV adherence interventions with a favorable value should become more integral components of HIV care

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

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

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

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

BACKGROUND: The decrement in utility attributable to side effects from combination antiretroviral therapy (CART) is unknown and likely to influence clinical decisions regarding CART initiation and cost-effectiveness. OBJECTIVE: To quantify the decrement in utility attributable to side effects from CART. METHODS: We estimated SF-6D utilities (quality-of-life weights on a scale from 0.29 [worst possible health] to 1.00 [perfect health]) from SF-12 scores among patients with HIV in the Veterans Aging Cohort Study by using a published and validated conversion algorithm. We then compared utilities among patients who: 1) did not have bothersome symptoms while taking CART; 2) had bothersome symptoms that they thought might be due to CART; and 3) had bothersome symptoms that they were confident were due to CART; we controlled for other characteristics known to influence quality of life and stratified analyses by CD4 count. RESULTS: Among 1864 patients with available data, symptoms perceived to be attributable to CART were associated with a mean (95% confidence interval) decrement in utility of 0.06 (0.05, 0.08) points in univariate analyses and 0.08 (0.06, 0.10) in multivariable analyses, clinically significant differences that are comparable to utility decrements reported for partial impotence or mild angina. Other significant predictors of changes in SF-6D utilities were hazardous alcohol consumption, recent drug use, cigarette smoking, homelessness, and African American race (R(2) = 0.12). Stratifying by CD4 count, symptoms attributable to CART side effects decreased utility by 0.03 to 0.08 points. CONCLUSIONS: Symptoms perceived to be related to CART are associated with a substantial decrement in utility

BACKGROUND: The optimal threshold for initiating HIV treatment is unclear. OBJECTIVE: To compare different thresholds for initiating HIV treatment. DESIGN: A validated computer simulation was used to weigh important harms from earlier initiation of antiretroviral therapy (toxicity, side effects, and resistance accumulation) against important benefits (decreased HIV-related mortality). DATA SOURCES: Veterans Aging Cohort Study (5742 HIV-infected patients and 11 484 matched uninfected controls) and published reports. TARGET POPULATION: Individuals with newly diagnosed chronic HIV infection and varying viral loads (10,000, 30,000, 100,000, and 300,000 copies/mL) and ages (30, 40, and 50 years). TIME HORIZON: Unlimited. PERSPECTIVE: Societal. INTERVENTION: Alternative thresholds for initiating antiretroviral therapy (CD4 counts of 200, 350, and 500 cells/mm3). OUTCOME MEASURES: Life-years and quality-adjusted life-years (QALYs). RESULTS OF BASE-CASE ANALYSIS: Although the simulation was biased against earlier treatment initiation because it used an upper-bound assumption for therapy-related toxicity, earlier treatment increased life expectancy and QALYs at age 30 years regardless of viral load (life expectancies with CD4 initiation thresholds of 500, 350, and 200 cells/mm3 were 18.2 years, 17.6 years, and 17.2 years, respectively, for a viral load of 10,000 copies/mL and 17.3 years, 15.9 years, and 14.5 years, respectively, for a viral load of 300,000 copies/mL), and increased life expectancies at age 40 years if viral loads were greater than 30 000 copies/mL (life expectancies were 12.5 years, 12.0 years, and 11.4 years, respectively, for a viral load of 300,000 copies/mL). RESULTS OF SENSITIVITY ANALYSIS: Findings favoring early treatment were generally robust. LIMITATIONS: Results favoring later treatment may not be valid. The findings may not be generalizable to women. CONCLUSION: This simulation suggests that earlier initiation of combination antiretroviral therapy is often favored compared with current recommendations