Transmission of antiretroviral-drug-resistant HIV-1 variants

被引:331
作者
Yerly, S
Kaiser, L
Race, E
Bru, JP
Clavel, F
Perrin, L [1 ]
机构
[1] Univ Hosp Geneva, Div Infect Dis, Virol Lab, CH-1211 Geneva 14, Switzerland
[2] Univ Hosp Geneva, Div Infect Dis, AIDS Unit, Geneva, Switzerland
[3] Hop Xavier Bichat, INSERM, Antiviral Res Lab, Paris, France
[4] Annecy Hosp Ctr, Div Infect Dis, Annecy, France
关键词
D O I
10.1016/S0140-6736(98)12262-6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Resistance of HIV-1 to antiretroviral drugs is the main cause of antiretroviral-treatment failure. We assessed the transmission of drug-resistant variants among individuals with primary HIV-1 infection. Methods Population-based sequencing of the viral reverse transcriptase and protease genes derived from plasma viral RNA was done in 82 consecutive individuals with documented primary HIV-1 infection from January, 1996, to July, 1998. Phenotypic resistance to protease inhibitors was assessed by recombinant virus assay in individuals with two or more mutations associated with resistance to protease inhibitors. Findings Zidovudine-resistance mutations were detected in seven (9%) of 82 individuals. Mutations associated with resistance to other reverse-transcriptase inhibitors (RTls) were detected in two individuals. Primary-resistance mutations associated with protease inhibitors (V82A, L90M) were detected in three (4%) of 70 individuals; two of these had also RTI-resistance mutations. Decreased sensitivity to three or four protease inhibitors was seen in three individuals, one of whom was infected with HIV-1 variants that harboured 12 mutations associated with resistance to multiple RTI and protease inhibitors. Interpretation To introduce the best antiretroviral treatment, resistance testing should be done in recently HIV-1-infected individuals.
引用
收藏
页码:729 / 733
页数:5
相关论文
共 26 条
  • [1] Reduced replication of 3TC-resistant HIV-1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme
    Back, NKT
    Nijhuis, M
    Keulen, W
    Boucher, CAB
    Essink, BBO
    vanKuilenburg, ABP
    vanGennip, AH
    Berkhout, B
    [J]. EMBO JOURNAL, 1996, 15 (15) : 4040 - 4049
  • [2] HIV-1 REVERSE TRANSCRIPTION - A TERMINATION STEP AT THE CENTER OF THE GENOME
    CHARNEAU, P
    MIRAMBEAU, G
    ROUX, P
    PAULOUS, S
    BUC, H
    CLAVEL, F
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1994, 241 (05) : 651 - 662
  • [3] CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
  • [4] HIV POPULATION-DYNAMICS IN-VIVO - IMPLICATIONS FOR GENETIC-VARIATION, PATHOGENESIS, AND THERAPY
    COFFIN, JM
    [J]. SCIENCE, 1995, 267 (5197) : 483 - 489
  • [5] IN-VIVO EMERGENCE OF HIV-1 VARIANTS RESISTANT TO MULTIPLE PROTEASE INHIBITORS
    CONDRA, JH
    SCHLEIF, WA
    BLAHY, OM
    GABRYELSKI, LJ
    GRAHAM, DJ
    QUINTERO, JC
    RHODES, A
    ROBBINS, HL
    ROTH, E
    SHIVAPRAKASH, M
    TITUS, D
    YANG, T
    TEPPLER, H
    SQUIRES, KE
    DEUTSCH, PJ
    EMINI, EA
    [J]. NATURE, 1995, 374 (6522) : 569 - 571
  • [6] Eron J, 1998, AIDS, V12, pS13
  • [7] Impact of antiretroviral combination therapies on AIDS surveillance reports in Switzerland
    Gebhardt, M
    Rickenbach, M
    Egger, M
    [J]. AIDS, 1998, 12 (10) : 1195 - 1201
  • [8] GRANT RM, 1998, ANTIVIR THER S, V3, P108
  • [9] A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less
    Hammer, SM
    Squires, KE
    Hughes, MD
    Grimes, JM
    Demeter, LM
    Currier, JS
    Eron, JJ
    Feinberg, JE
    Balfour, HH
    Dayton, LR
    Chodakewitz, JA
    Fischl, MA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1997, 337 (11) : 725 - 733
  • [10] Nevirapine-resistant human immunodeficiency virus: Kinetics of replication and estimated prevalence in untreated patients
    Havlir, DV
    Eastman, S
    Gamst, A
    Richman, DD
    [J]. JOURNAL OF VIROLOGY, 1996, 70 (11) : 7894 - 7899