title: 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.
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.
authors: Tibotec BVBA, Beerse, Belgium. lrimsky@its.jnj.com
authors: Laurence
authors: L
authors: Rimsky
authors: Johan
authors: J
authors: Vingerhoets
authors: Veerle
authors: V
authors: Van Eygen
authors: Joseph
authors: J
authors: Eron
authors: Bonaventura
authors: B
authors: Clotet
authors: Annemie
authors: A
authors: Hoogstoel
authors: Katia
authors: K
authors: Boven
authors: Gaston
authors: G
authors: Picchio
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use; D003521:Cyclopropanes; D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009570:Nitriles / Q000627:therapeutic use*; D010641:Phenotype; D011743:Pyrimidines / Q000627:therapeutic use*; D000068696:Rilpivirine; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009570:Nitriles; D011743:Pyrimidines; D000068696:Rilpivirine; C098320:efavirenz