Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1994 Mar;68(3):1660-6.

Nevirapine Resistance Mutations of Human Immunodeficiency Virus Type 1 Selected During Therapy

Free PMC article

Nevirapine Resistance Mutations of Human Immunodeficiency Virus Type 1 Selected During Therapy

D D Richman et al. J Virol. .
Free PMC article


Drug susceptibility and mutations in the reverse transcriptase (RT) gene were analyzed with 167 virus isolates from 38 patients treated with nevirapine, a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) RT. Resistant isolates emerged quickly and uniformly in all patients administered nevirapine either as monotherapy or in combination with zidovudine (AZT). Resistance developed as early as 1 week, indicating rapid turnover of the virus population. The development of resistance was associated with the loss of antiviral drug activity as measured by CD4 lymphocyte counts and levels of HIV p24 antigen and RNA in serum. In addition to mutations at amino acid residues 103, 106, and 181 that had been identified by selection in cell culture, mutations at residues 108, 188, and 190 were also found in the patient isolates. Sequences from patient clones documented cocirculating mixtures of populations of different mutants. The most common mutation with monotherapy, tyrosine to cysteine at residue 181, was prevented from emerging by coadministration of AZT, which resulted in the selection of alternative mutations. The observations documented that, under selective drug pressure, the circulating virus population can change rapidly, and many alternative mutants can emerge, often in complex mixtures. The addition of a second RT inhibitor, AZT, significantly altered the pattern of mutations in the circulating population of HIV.

Similar articles

See all similar articles

Cited by 156 articles

See all "Cited by" articles


    1. Nucleic Acids Res. 1988 Nov 25;16(22):10881-90 - PubMed
    1. Antimicrob Agents Chemother. 1993 Aug;37(8):1576-9 - PubMed
    1. Science. 1989 Dec 1;246(4934):1155-8 - PubMed
    1. Science. 1990 Dec 7;250(4986):1411-3 - PubMed
    1. Biochemistry. 1991 Feb 26;30(8):2022-6 - PubMed

Publication types

MeSH terms