Skip Navigation LinksHome > January 1, 2012 - Volume 59 - Issue 1 > Genotypic and Phenotypic Characterization of HIV-1 Isolates...
JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31823df4da
Clinical Science

Genotypic and Phenotypic Characterization of HIV-1 Isolates Obtained From Patients on Rilpivirine Therapy Experiencing Virologic Failure in the Phase 3 ECHO and THRIVE Studies: 48-Week Analysis

Rimsky, Laurence PhD*; Vingerhoets, Johan PhD*; Van Eygen, Veerle MSc*; Eron, Joseph MD; Clotet, Bonaventura MD; Hoogstoel, Annemie MSc*; Boven, Katia MD§; Picchio, Gaston PhD§

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Abstract

Abstract: Genotypic and phenotypic characterization was performed of HIV-1 isolates from treatment-naive HIV-1–infected patients experiencing virologic failure (VF) during treatment with the nonnucleoside reverse transcriptase inhibitor (NNRTIs) rilpivirine or efavirenz in the pooled phase 3 studies ECHO and THRIVE. Among 686 patients receiving rilpivirine, 72 (10%) experienced VF versus 39 of 682 (6%) receiving efavirenz. In patients with low baseline viral load (VL) ≤100,000 copies per milliliter, the proportions of rilpivirine VFs (19 of 368) and efavirenz VFs (16 of 330) were the same (5%). In patients with high baseline VL >100,000 copies per milliliter, the proportion of VFs was higher with rilpivirine (53 of 318; 17%) than efavirenz (23 of 352; 7%). The rate of rilpivirine VF was comparable between HIV-1 subtype B–infected (11%) and nonsubtype B–infected (8%) patients. The absolute number of VFs with treatment-emergent NNRTI resistance-associated mutations (RAMs) was higher for rilpivirine (most commonly E138K or K101E) than efavirenz (most commonly K103N), but relative proportions were similar [63% (39 of 62) vs. 54% (15 of 28), respectively]. More rilpivirine VFs had treatment-emergent nucleoside/nucleotide reverse transcriptase inhibitor RAMs than efavirenz VFs [68% (42 of 62) versus 32% (9 of 28), respectively], most commonly M184I and M184V. The proportion of rilpivirine VFs with RAMs in patients with low baseline VL was lower than in those with high baseline VL [38% (6 of 16) versus 72% (33 of 46) for NNRTI RAMs and 44% (7 of 16) versus 76% (35 of 46) for nucleoside/nucleotide reverse transcriptase inhibitor RAMs, respectively]. In summary, VF and treatment-emergent reverse transcriptase RAMs were similar at low baseline VL but more frequent at high baseline VL in rilpivirine-treated than in efavirenz-treated patients. The frequent emergence of E138K, especially in combination with M184I, in rilpivirine VFs is a unique finding of these trials.

© 2012 Lippincott Williams & Wilkins, Inc.

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