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Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy.

Abstract：

: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.

journal_name

J Virol

journal_title

Journal of virology

authors

Richman DD,Havlir D,Corbeil J,Looney D,Ignacio C,Spector SA,Sullivan J,Cheeseman S,Barringer K,Pauletti D

doi

10.1128/JVI.68.3.1660-1666.1994

subject

Has Abstract,Author List Incomplete

pub_date

1994-03-01 00:00:00

pages

1660-6

issue

3

eissn

0022-538X

issn

1098-5514

journal_volume

68

pub_type

杂志文章

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