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Racial Differences in Virologic Failure Associated With Adherence and Quality of Life on Efavirenz-Containing Regimens for Initial HIV Therapy: Results of ACTG A5095

Schackman, Bruce R PhD*; Ribaudo, Heather J PhD; Krambrink, Amy MS; Hughes, Valery FNP; Kuritzkes, Daniel R MD§; Gulick, Roy M MD, MPH

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15th, 2007 - Volume 46 - Issue 5 - p 547-554
doi: 10.1097/QAI.0b013e31815ac499
Clinical Science

Background: Blacks had higher rates of virologic failure than whites on efavirenz-containing regimens in the AIDS Clinical Trials Group (ACTG) A5095 study; preliminary analyses also suggested an association with adherence. We rigorously examined associations over time among race, virologic failure, 4 self-reported adherence metrics, and quality of life (QOL).

Methods: ACTG A5095 was a double-blind placebo-controlled study of treatment-naive HIV-positive patients randomized to zidovudine/lamivudine/abacavir versus zidovudine/lamivudine plus efavirenz versus zidovudine/lamivudine/abacavir plus efavirenz. Virologic failure was defined as confirmed HIV-1 RNA ≥200 copies/mL at ≥16 weeks on study. The zidovudine/lamivudine/abacavir arm was discontinued early because of virologic inferiority. We examined virologic failure differences for efavirenz-containing arms according to missing 0 (adherent) versus at least 1 dose (nonadherent) during the past 4 days, alternative self-reported adherence metrics, and QOL. Analyses used the Fisher exact, log rank tests, and Cox proportional hazards models.

Results: The study population included white (n = 299), black (n = 260), and Hispanic (n = 156) patients with ≥1 adherence evaluation. Virologic failure was associated with week 12 nonadherence during the past 4 days for blacks (53% nonadherent failed vs. 25% adherent; P < 0.001) but not for whites (20% nonadherent failed vs. 20% adherent; P = 0.91). After adjustment for baseline covariates and treatment, there was a significant interaction between race and week 12 adherence (P = 0.02). In time-dependent Cox models using self-reports over time to reflect recent adherence, there was a significantly higher failure risk for nonadherent subjects (hazard ratio [HR] = 2.07; P < 0.001). Significant race-adherence interactions were seen in additional models of adherence: missing at least 1 medication dose ever (P = 0.04), past month (P < 0.01), or past weekend (P = 0.05). Lower QOL was significantly associated with virologic failure (P < 0.001); there was no evidence of an interaction between QOL and race (P = 0.39) or adherence (P = 0.51) in predicting virologic failure.

Conclusions: There was a greater effect of nonadherence on virologic failure in blacks given efavirenz-containing regimens than in whites. Self-reported adherence and QOL are independent predictors of virologic failure.

From the *Department of Public Health, Weill Medical College, New York, NY; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; ‡Division of International Medicine and Infectious Diseases, Weill Medical College, New York, NY; and the §Section of Retroviral Therapeutics, Brigham and Women's Hospital and Division of AIDS, Harvard Medical School, Boston, MA.

Received for publication April 9, 2007; accepted September 10, 2007.

Supported by grants AI 68634 (Statistical and Data Management Center of the AIDS Clinical Trials Group [ACTG]), AI 68636 (ACTG central grant), AI 51966 (R.M. Gulick), AI 69419 (Cornell AIDS Clinical Trials Unit), DA 017179 (B.R. Schackman), M01RR 00047 (Cornell General Clinical Research Center [GCRC]), AI 27659 (D.R. Kuritzkes), and RR 02635 (Brigham and Women's Hospital GCRC).

Presented in part at the XVI International AIDS Conference, Toronto, Ontario, Canada, August 13-18, 2006 (abstract TUPE0113).

Correspondence to: Bruce R. Schackman, PhD, Department of Public Health, Weill Medical College of Cornell University, 411 East 69th Street, New York, NY 10021 (e-mail: brs2006@med.cornell.edu).

© 2007 Lippincott Williams & Wilkins, Inc.