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 RegimensE. J. Edelman1-3, K. Gordon3, M. Rodriguez-Barradas4, A.C. Justice1-3 for the VACS Project Team

Robert Wood Johnson Clinical Scholars Program1~Yale University School of Medicine, New Haven, CT2

VA Connecticut Healthcare System, West Haven, CT3

Michael E. De Bakey VAMC and Baylor College of Medicine, Houston, Texas4

INTRODUCTIONBackground

•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.

METHODSData 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

Characteristic Estimate 95% CI Estimate 95% CI

EFV/FTC/TDF Use 2.48 1.07, 3.89  1.16  -0.06, 2.39 # Bothersome Symptoms -- -- -0.96 -1.04, -0.88VACS Index Score -- -- -0.10 -0.12, -0.08cART adherence -- --  -0.30  -0.83, 0.22cART-naïve status -- -- 0.25 -2.12, 2.62

Characteristic Other cARt

% (n)n= 1500

EFV/FTC/TDF% (n)

n= 259p value

Age, Mean (SD) 54 (9) 53 (8) 0.01

Sex (male) 98 (1463) 98(255) 0.36

Race/Ethnicity:   0.07

White 21 (322) 16 (42)

Black 64 (962) 73 (188)

Hispanic 10 (155) 8 (20)

Other 4 (61) 3 (9)

Hepatitis C 46 (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

Symptom UOR 95% CI AOR 95% CI

Numbness/tingling in hands/feet       Other cART ref n/a ref n/a EFV/FTC/TDF 0.71 0.54 - 0.93 0.74 0.56 - 0.97Nausea/vomiting       Other cART ref n/a ref n/a EFV/FTC/TDF 0.59 0.38 - 0.91 0.60 0.39 - 0.94Skin problems/rash/itching       Other cART Ref n/a ref n/a EFV/FTC/TDF 0.74 0.56 - 0.98 n/a n/a