Human Immunodeficiency Virus Type 1 Mutations Selected in Patients Failing Efavirenz Combination Therapy

• DOI: 10.1128/aac.44.9.2475-2484.2000
• Publication Date: 2002-07-27T10:06:42Z
• Authors: Lee T. Bacheler; Elizabeth D. Anton; Phil Kudish; David Baker; Julie Bunville; Karen Krakowski; Laura Bolling; Monette Aujay; Xin Victoria Wang; Dawn Ellis; Mary F. Becker; Amy L. Lasut; Henry J. George; Daniel R. Spalding; Greg Hollis; Kenneth Abremski
• Keywords: Efavirenz; Indinavir; Stavudine; Reverse-transcriptase inhibitor

Efavirenz is a potent and selective nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Nucleotide sequence analyses the protease RT genes (coding region for amino acids to 229) multiple cloned HIV-1 genomes from found in plasma patients phase II clinical studies efavirenz combination therapy were undertaken order identify spectrum mutations plasma-borne associated with virological treatment failure. A K103N substitution was gene mutation most frequently observed among samples whom including failed, occurring at least 90% cases efavirenz-indinavir or efavirenz-zidovudine (ZDV)-lamivudine (3TC) V108I P225H frequently, predominantly viral that also contained other (NNRTI) resistance mutations. L100I, K101E, K101Q, Y188H, Y188L, G190S, G190A, G190E observed. V106A, Y181C, Y188C mutations, which have been high levels NNRTIs, rare patient this study, both before after exposure efavirenz. The failure similar initially dosed 200, 400, 600 mg once day treated indinavir, stavudine, ZDV-3TC. proportion carrying NNRTI usually K103N, increased dramatically time initial load rebound Viruses multiple, linked especially K103N-V108I K103N-P225H double mutants, accumulated more slowly following emergence mutant viruses.