Timothy Juday

The Risk of Long-term Morbidity and Mortality in Patients With Chronic Hepatitis C: Results From an Analysis of Data From a Department of Veterans Affairs Clinical Registry

IMPORTANCE The impact of viral load suppression, genotype, race, and other factors on the risk of late-stage liver-related events in patients with hepatitis C (HCV) has been assessed previously using data from small observational cohorts or clinical trials. Data from large real-world practice samples are needed to improve risk factor estimates for late-stage liver events and death in HCV. OBJECTIVE To describe the natural history of HCV in real-world clinical practice. DESIGN, SETTING, AND PARTICIPANTS Observational cohort study. Patients with a detectable viral load (>25 IU/mL) and a recorded baseline genotype were selected from the Veterans Affairs (VA) HCV clinical registry (CCR), which compiles electronic medical records data from 1999 to present. EXPOSURES Risk factors included genotype, race, age, sex, and time to achieving an observed undetected viral load. MAIN OUTCOMES AND MEASURES The primary outcomes were time to death and time to a composite of liver-related clinical events. Secondary outcomes included the components of the composite clinical outcome. Outcomes were measured using a time-to-event format and were analyzed using Cox proportional hazards models. RESULTS A total of 28,769 of 360,857 unique HCV CCR patients met all study criteria. Only 24.3% of patients received treatment, and 16.4% of treated patients (4.0% of all patients) achieved an undetectable viral load. The unadjusted death rates were 6.8 (95% CI, 6.0-7.7) per 1000 person-years for patients who achieved viral load suppression vs 21.8 (95% CI, 21.5-22.2) deaths per 1000 person-years in patients who did not achieve this goal. Cox model results found that achieving viral suppression reduced risk of the composite clinical end point by 27% (hazard ratio [HR], 0.73 [95% CI, 0.66-0.82]) and the risk of death by 45% (HR, 0.55 [95% CI, 0.47-0.64]). Genotype 2 patients were at significantly lower risk, and genotype 3 patients were at higher risk for all study outcomes relative to genotype 1. Black patients were at lower risk for all liver events than white patients. CONCLUSION AND RELEVANCE Achieving an undetectable viral load was associated with decreased hepatic morbidity and mortality. It remains to be determined whether newer treatment regimens can offer higher response rates with fewer adverse effects in real-world settings.

Factors associated with complete adherence to HIV combination antiretroviral therapy.

Abstract Purpose: To assess factors associated with adherence, particularly pill burden, to combination antiretroviral therapy (cART) using multivariate models. Method: A cross-sectional survey of US adults with a self-reported diagnosis of HIV/AIDS was conducted between April and May 2007. Respondents on a cART regimen of at least 2 nucleoside reverse transcriptase inhibitors plus at least 1 protease inhibitor or non-nucleoside reverse transcriptase inhibitor (n = 461) were included in the analytic sample. Multiple logistic regression models determined independent predictors of complete adherence (defined as never missing or skipping an antiretroviral dose). Results: Fifty-four percent of respondents reported complete adherence to cART. Adherent respondents reported a lower percentage of hospitalizations (11% vs 28%; P < .0001) and emergency room visits (26% vs 34%; P < .09). Respondents taking the single tablet efavirenz/emtricitabine/tenofovir fixed-dose regimen were significantly more likely to have complete adherence than respondents taking other cART regimens (odds ratio [OR] 2.1, P < .05), and higher imputed daily HIV pill count was associated with lower likelihood of complete adherence (OR 0.93, P < .05). Conclusion: This study shows the negative impact of higher pill burden on medication adherence, an important factor associated with treatment outcomes in patients with HIV/AIDS.

A retrospective study of HIV antiretroviral treatment persistence in a commercially insured population in the United States

This study examined factors associated with persistence (time from initiation to discontinuation of treatment) on initial antiretroviral (ARV) therapy in commercially insured HIV patients in the United States, a population not well researched. This retrospective analysis of US health insurance claims data from 1 January 2003 to 30 June 2008 included treatment-naive patients aged 18–65 years with an HIV diagnosis receiving ARV therapy consisting of at least two individual nucleoside reverse transcriptase inhibitors (NRTIs) or one fixed-dose combination NRTI, plus at least one nonnucleoside reverse transcriptase inhibitor (NNRTI) or one protease inhibitor (PI), with or without ritonavir. Descriptive statistics, Kaplan-Meier survival estimation, and Cox proportional hazards regression models were completed. Patients were considered persistent until any component of the regimen was modified or there was a gap in treatment >90 days. A total of 2460 patients met full inclusion criteria (1388 NNRTI and 1072 PI). Mean (SD) time to discontinuation for NNRTI- vs PI-based regimens was 370 (346) vs 295 (338) days (p<0.001). Female sex, substance use, low comorbidity score, index year before 2007, geographical region, and taking a lopinavir/ritonavir regimen predicted discontinuation. Relative to NNRTI-based regimens, PI-based regimens demonstrated a greater risk of discontinuation (hazard ratio [HR], 1.32; p<0.001). The fixed-dose efavirenz/emtricitabine/tenofovir combination yielded the lowest risk of discontinuation (HR, 0.39; p<0.001). HIV treatment persistence was longer with NNRTI-based regimens than PI-based regimens. The fixed-dose regimen of once-daily efavirenz/emtricitabine/tenofovir had the lowest risk of discontinuation.

HIV Care Providers Emphasize the Importance of the Ryan White Program for Access to and Quality of Care

With the implementation of the Affordable Care Act (ACA) under way, some policy makers have questioned the continued relevance of the Ryan White HIV/AIDS Program as a safety net for people living with HIV/AIDS. We surveyed HIV care providers to understand the role of the Ryan White Program and to identify concerns regarding the ACA implementation. We also addressed whether the program is still relevant after ACA implementation and, if so, what elements should be retained. We found that providers consider the Ryan White Program to be critical in facilitating high-quality care for people living with HIV/AIDS. Most of the providers highlighted the programs support for providing medical and nonmedical case management as especially valuable and important to the entire continuum of care and for all patient subpopulations. Whether care is supplied by the Ryan White Program, Medicaid, or other means, our findings suggest that case management services will remain critical in treating HIV/AIDS as the health care landscape continues to evolve.

Impact of health care payer type on HIV stage of illness at time of initiation of antiretroviral therapy in the USA

There is evidence that earlier initiation of HIV antiretroviral therapy (ART) is associated with better outcomes, including lower morbidity and mortality. Based on recent studies indicating that Medicaid enrollees are more likely to have suboptimal access to medical care, we hypothesized that HIV severity at time of ART initiation is worse for Medicaid patients than patients with other health care coverage. We conducted a US retrospective analysis of GE Centricity Outpatient Electronic Medical Records spanning 1 January 1997 through 30 September 2009. Subjects included all adult HIV patients initiating first-line ART who had CD4+ results within 90 days pre-initiation. HIV stage was defined using CD4 ranges: >500 (n=520), 351–500 (n=379), 201–350 (n=580), or ≤200 (n=406) cells/mm3, with lower CD4 count being indicative of increased disease severity. Payer type was defined as the patients primary payer: Medicaid, Medicare, commercial insurance, self-pay or other/unknown. After controlling for demographic and clinical covariates, cumulative logit models assessed the effect of payer type on HIV stage at ART initiation. The study included 1885 subjects with the primary payer being Medicaid (n=218), Medicare (n=330), commercial insurance (n=538), self-pay (n=159) or other/unknown (n=640). Final logit models demonstrated that, compared to patients on Medicaid, the odds of initiating ART at a higher CD4 range were significantly greater for those commercially insured (odds ratio [OR]=1.53; P=0.005), self-paying (OR=1.56; P=0.023) and other/unknown (OR=1.79; P<0.001) and similar for patients enrolled in Medicare (OR=1.11; P=0.521). Medicaid patients initiated ART at a more advanced stage of HIV than patients who were commercially insured, self-paying, or had other/unknown coverage. With HIV treatment guidelines now supporting ART initiation in patients with higher CD4 counts, these findings underscore the need for mitigating barriers, particularly in the Medicaid population, that may delay treatment initiation.

Cost effectiveness of atazanavir-ritonavir versus lopinavir-ritonavir in treatment-naïve human immunodeficiency virus-infected patients in the United States

Abstract Objective: To evaluate lifetime cost effectiveness of atazanavir-ritonavir (ATV + r) versus lopinavir-ritonavir (LPV/r), both with tenofovir-emtricitabine, in US HIV-infected patients initiating first-line antiretroviral therapy. Methods: A Markov microsimulation model was developed to calculate quality-adjusted life-years (QALYs) based on CD4 and HIV RNA levels, coronary heart disease (CHD), AIDS, opportunistic infections (OIs), diarrhea, and hyperbilirubinemia. A million-member cohort of HIV-1-infected, treatment-naïve adults progressed at 3-month intervals through eight health states. Baseline characteristics, virologic suppression, cholesterol changes, and diarrhea and hyperbilirubinemia rates were based on 96-week CASTLE trial results. HIV mortality, OI rates, adherence, costs, utilities, and CHD risk were from literature and experts. Limitations: The incremental cost-effectiveness ratio (ICER) may be overestimated because the ATV + r treatment effect was based on an intention-to-treat analysis. The QALY weights used for diarrhea, hyperbilirubinemia, and CHD events are uncertain; however, the ICER remained <

Data-Driven Decision-Making Tools To Improve Public Resource Allocation For Care And Prevention Of HIV/AIDS

50,000/QALY when these values were varied in sensitivity analyses. Results: ATV + r patients received first-line therapy longer than LPV/r patients (97.3 vs. 70.7 months), had longer quality-adjusted survival (11.02 vs. 10.76 years), similar overall survival (18.52 vs. 18.51 years), and higher costs (

Cost-effectiveness of the once-daily efavirenz/emtricitabine/tenofovir tablet compared with the once-daily elvitegravir/cobicistat/emtricitabine/tenofovir tablet as first-line antiretroviral therapy in HIV-infected adults in the US

275,986 vs. 269,160). ATR + r patients had lower rates of AIDS (19.08 vs. 20.05 cases/1,000 patient-years), OIs (0.44 vs. 0.52), diarrhea (1.27 vs. 6.26), and CHD events (5.44 vs. 5.51), but higher hyperbilirubinemia rates (6.99 vs. 0.25). ATV + r added 0.26 QALYs at a cost of

Adherence, persistence, healthcare utilization, and cost benefits of guideline-recommended hepatitis B pharmacotherapy

6826, for

Comparative Incidence and Health Care Costs of Medically Attended Adverse Effects among U.S. Medicaid HIV Patients on Atazanavir- or Darunavir-Based Antiretroviral Therapy

26,421/QALY. Conclusions: By more effectively reducing viral load with less gastrointestinal toxicity and a better lipid profile, ATV + r lowered rates of AIDS and CHD, increased quality-adjusted survival, and was cost effective (<