1. Generously supported by the Robert Wood Johnson Foundation Clinical Scholars Program, Department of Veteran Affairs, and National Institutes of Health, NIAAA (U10-AA13566). Symptoms on EFV/FTC/TDF vs. Other cART Regimens E. J. Edelman 1-3, K. Gordon 3, M. Rodriguez-Barradas 4, A.C. Justice 1-3 for the VACS Project Team Robert Wood Johnson Clinical Scholars Program 1 ~Yale University School of Medicine, New Haven, CT 2 VA Connecticut Healthcare System, West Haven, CT 3 Michael E. De Bakey VAMC and Baylor College of Medicine, Houston, Texas 4 INTRODUCTION Background Drug side effects are an important cause of symptoms among patients on combination antiretroviral therapy. HIV management of treatment-naïve HIV-infected patients has converged on Efavirenz, Emtricitabine and Tenofovir (EFV/FTC/TDF), marketed as Atripla. Gaps in the Current Literature Existing studies of patient tolerability of the most common treatment regimens, including EFV/FTC/TDF, are limited. Purpose To describe the characteristics of the patients prescribed EFV/FTC/TDF. To determine the association between symptoms and EFV/FTC/TDF use, with and without adjusting for disease severity (as measured by VACS index) and adherence. To determine the association between Health-Related Quality of Life (HRQoL) and EFV/FTC/TDF use, unadjusted and adjusted for symptoms, disease severity, and treatment characteristics. METHODS Data Source: Veterans Aging Cohort Study HIV-infected Veterans from Infectious Disease Clinics in Manhattan, Bronx, Washington D.C., Baltimore, Pittsburgh, Atlanta, Houston, Los Angeles. Secondary data analysis of data collected between 2008 and 2009. Survey data, electronic medical record and administrative data. Analytic sample restricted to patients prescribed any cART for > 3 months with available symptom, pharmacy and adherence data. Variables HIV Symptom Index – degree of bother of 20 symptoms over the past four weeks. # Bothersome Symptoms – count of symptoms that bothered patient “at least a little.” VACS Index – prognostic index; used to adjust for disease severity, range 0 – 100. Adherence – calculated using fill/refill pharmacy data, range 0 – 1. HRQoL - Physical Component Scale of SF-12, range 0 -100. Analysis Descriptive statistics using chi-square for categorical variables, and t-tests or Kruskal- Wallis test for continuous variables. Logistic regression to assess the association between EFV/FTC/TDF use and symptoms, unadjusted and then adjusted for VACS Index and adherence. Linear regression to asses the association between EFV/FTC/TDF use and HRQoL, unadjusted and then adjusted for symptoms, disease severity, and treatment characteristics. RESULTS DISCUSSION Table 1. Patient Characteristics by EFV/FTC/TDF Use, n = 1,759 *Notes: Race, sex and Hepatitis C were at baseline. Symptoms, hemoglobin, CD4 and HIV-1 RNA were based on the last follow-up date. Bold, italicized text indicates statistically significant. Table 3. The Association between HRQoL and EFV/FTC/TDF Use, unadjusted and adjusted, Using Linear Regression, n = 1,759 Summary In comparison to patients not on EFV/FTC/TDF, patients on EFV/FTC/TDF were younger, less likely to be infected with Hepatitis C, and less sick as assessed by the VACS Index and other laboratory values. Patients on EFV/FTC/TDF were significantly less likely to report numbness/ tingling in hands/feet; nausea/vomiting; and skin problems/rash/itching in comparison to patients on other antiretroviral agents. Patients on EFV/FTC/TDF continue to be less likely to report particular symptoms even after adjusting for disease severity and adherence. EFV/FTC/TDF use is associated with HRQoL, but this relationship is explained by symptom count and disease severity. Implications As new antiretroviral agents, including combination pills become available, patient-reported symptoms should be routinely assessed. *Notes: UOR – unadjusted odds ratio; AOR – adjusted odds ratio; CI – confidence interval. Figure 1. Symptoms on EFV/FTC/TDF vs. Other cART, n = 1,759 Table 2. Symptoms Significantly Associated with EFV/FTC/TDF Use, with and without adjusting for VACS Index and Adherence, Using Logistic Regression, n = 1,759 CharacteristicEstimate95% CIEstimate95% CI EFV/FTC/TDF Use2.481.07, 3.89 1.16 -0.06, 2.39 # Bothersome Symptoms-- -0.96-1.04, -0.88 VACS Index Score-- -0.10-0.12, -0.08 cART adherence-- -0.30 -0.83, 0.22 cART-naïve status-- 0.25-2.12, 2.62 Characteristic Other cARt % (n) n= 1500 EFV/FTC/TDF % (n) n= 259 p value Age, Mean (SD)54 (9)53 (8)0.01 Sex (male)98 (1463)98(255)0.36 Race/Ethnicity: 0.07 White21 (322)16 (42) Black64 (962)73 (188) Hispanic10 (155)8 (20) Other4 (61)3 (9) Hepatitis C46 (692)33 (86)<0.001 Total Bothersome Symptoms, mean (SD)6.6 (5.3)5.9 (5.3)0.03 Adherence, mean (SD)0.8 (0.9)0.8 (0.3)0.92 Days on cART, median (range)211 (0, 365)245 (31, 365)<0.001 Hemoglobin, mean (SD)13.7 (1.8)14.0 (1.6)0.05 VACS Index Score, mean (SD)34 (22)28 (20)<0.001 CD4, median (range)421 (2, 3766)488 (9, 1940)0.001 Viral load, median (range)75 (0, 750000)51 (40, 524661)<0.001 SymptomUOR95% CIAOR95% CI Numbness/tingling in hands/feet Other cARTrefn/arefn/a EFV/FTC/TDF0.710.54 - 0.930.740.56 - 0.97 Nausea/vomiting Other cARTrefn/arefn/a EFV/FTC/TDF0.590.38 - 0.910.600.39 - 0.94 Skin problems/rash/itching Other cARTRefn/arefn/a EFV/FTC/TDF0.740.56 - 0.98n/a