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Outcomes of Abacavir- and Efavirenz-based HAART: Comparison of ACTG 5095 Trial Results with Observational Cohort Studies
Michael Mugavero*1, M May2, H Ribaudo3, J Sterne2, S Napravnik4, M Egger5, M Saag1, R Gulick6, and ACTG and ART-CC
1Univ of Alabama at Birmingham, US; 2Univ of Bristol, UK; 3Harvard Sch of Publ Hlth, Boston, MA, US; 4Univ of North Carolina at Chapel Hill, US; 5Univ of Berne, Switzerland; and 6Weill Med Coll of Cornell Univ, New York, NY, US
Background: Randomized controlled trials are the
study design of choice for evaluating the effects of ART, but trials often
focus on virologic suppression, rather than clinical endpoints. Large
observational cohort studies have the power to examine clinical outcomes, but
results may be affected by confounding by indication. We compared the ACTG 5095
trial (A5095) with data from the ART Cohort Collaboration (ART-CC), 15 cohort
studies in Europe and North America.
Methods: We compared efavirenz (EFV) vs abacavir (ABC)
(combined with zidovudine/lamivudine [ZDV/3TC] or stavudine [d4T]/3TC)
stratifying by study design, and A5095 vs ART-CC stratifying by third drug in
ARV-naïve patients starting ART. A5095 data and ART-CC data were analyzed using
identical logistic regression models to evaluate 24-week virologic failure
(>400 copies/mL), and Cox models to compare 48-week progression to AIDS or
death, adjusting for age, sex, baseline CD4 count and viral load.
Results: We identified 5796 patients who met inclusion
criteria: 753 from A5095 (ABC = 377, EFV = 376) and 5043 from ART-CC (ABC = 2009,
EFV = 3034). Overall, virologic failure was observed in 13.8% of A5095 patients
(89 of 643) and 18.6% of ART-CC patients (813 of 4368) with available 24-week viral
load measures (p <0.01) and 3.1% (23 of 753), and 6.9% (350 of 5043)
progressed to AIDS or death (p <0.01). Prognostic factors were well
balanced in A5095. In ART-CC, patients starting with ABC had higher median CD4
counts than patients starting with EFV (251 vs 209 cells).
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Viral failure and clinical progression in patients
starting ABC- and EFV-based regimens
in ACTG 5095 and ART-CC
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Odds Ratio (95%CI) for virologic failure
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Hazard ratio (95%CI) for AIDS/death
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EFV vs. ABC
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Crude
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Adj.
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Crude
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Adj.
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ACTG
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0.64 (0.41 to 1.01)
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0.57 (0.36 to 0.90)
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0.77 (0.34 to 1.75)
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0.66 (0.28 to 1.53)
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ART-CC
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0.47 (0.40 to 0.55)
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0.45 (0.38 to 0.53)
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1.42 (1.13 to 1.77)
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0.99 (0.78 to 1.25)
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ACTG vs. ART-CC
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ABC
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0.58 (0.42 to 0.81)
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0.45 (0.32 to 0.64)
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0.60 (0.34 to 1.06)
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0.40 (0.22 to 0.73)
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EFV
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0.80 (0.57 to 1.13)
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0.78 (0.54 to 1.13)
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0.33 (0.17 to 0.62)
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0.37 (0.19 to 0.72)
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Conclusions: Patients on EFV were less likely to
experience virologic failure in both A5095 and ART-CC. Of note, EFV-based
regimens performed similarly in ART-CC and A5095, while virologic responses to
ABC-regimens were considerably better in A5095 compared to ART-CC. There was no
clear evidence of differences in clinical progression between EFV and ABC, but
the attenuation of the hazard ratio for AIDS/death after adjustment for
covariates in the ART-CC suggests residual confounding by indication in the
observational data. Clinical progression rates were higher in ART-CC than
A5095, independently of the regimen used.
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