Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naive patients and their impact on the virological failure

被引:46
作者
Balduin, Melanie [1 ]
Oette, Mark [2 ]
Daeumer, Martin P. [3 ]
Hoffmann, Daniel [4 ]
Pfister, Herbert J. [1 ]
Kaiser, Rolf [1 ]
机构
[1] Univ Cologne, Inst Virol, D-50935 Cologne, Germany
[2] Univ Dusseldorf, Clin Gastroenterol Hepatol & Infect Dis, Dusseldorf, Germany
[3] Inst Immunol & Genet, Kaiserslautern, Germany
[4] Univ Duisburg Essen, Ctr Med Biotechnol, Essen, Germany
关键词
Minority resistance; Therapy-naive patients; Non-nucleoside reverse transcriptase inhibitors; IMMUNODEFICIENCY-VIRUS TYPE-1; DRUG-RESISTANT HIV-1; FAILING ANTIRETROVIRAL THERAPY; TREATMENT INTERRUPTION; PROTEASE INHIBITORS; IN-VIVO; POPULATIONS; MUTATIONS; EVOLUTION; INDIVIDUALS;
D O I
10.1016/j.jcv.2009.03.002
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Background and objectives: Minority HIV-1 populations with resistance mutations might result in therapy failure. The prevalence of transmitted minorities in therapy-naive patients and their influence on the virological outcome of the first-line-therapy need clarification. Study design: The HIV reverse transcriptase (RT) of 159 therapy-naive patients from the RESINA-cohort was genotyped. The relative amount of RT-K103N was measured by primer specific PCR. The response to first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-therapy was evaluated. Results: Bulk-sequencing detected 1 NNRT1 mutation (no K103N) in six patients (1.26%). K103N minorities were found in 20.1% of the samples, more frequently in HIV-1 non-B subtypes (40.6%) than in subtype B (15.0%) (p = 0.0025). NNRTI treatment failed after 12 weeks in 24% of 17 patients with minority, but only in 15% of 67 patients without minority. Conclusions: K103N minorities were found in 20.1% of the patients, whereas the prevalence of major K103N populations was 3% in the total RESINA-cohort. K103N minorities were more frequent in non-B subtypes. There is some evidence for a higher risk of NNRTI-treatment failure in patients with K103N minorities; however, the majority of patients with minority underwent a successful first-line-treatment. (C) 2009 Published by Elsevier B.V.
引用
收藏
页码:34 / 38
页数:5
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