Genotypic resistance and the treatment of HIV-1 infection in Espirito Santo, Brazil

被引:11
作者
Pilcher, CD
Perkins, MD
Fiscus, SA
Johnston, DM
Dietze, R
Duque, UH
Zago, AM
Assad-Antunes, F
Eron, JJ
机构
[1] Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
[3] Duke Univ, Dept Med, Durham, NC USA
[4] Lab Corp Amer, Ctr Mol Biol, Res Triangle Pk, NC USA
[5] Univ Fed Espirito Santo, Ctr Biomed, Vitoria, ES, Brazil
关键词
D O I
10.1086/314709
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Before December 1997, in Espirito Santo, Brazil, combination antiretroviral therapy was used without routine virologic or immunologic monitoring. To examine consequences of therapy in this setting, clinical information, human immunodeficiency virus type 1 (HIV-1) RNA levels, CD4 cell counts, and protease and reverse transcriptase sequences were determined for consecutive HIV-1-infected outpatients. Of 48 treatment-naive individuals, 11 were started on therapy for HIV-related symptoms; however, 44 (92%) had an RNA level >20,000 copies/mL, a CD4 cell count <500/mm(3), or symptoms, Eighteen (51%) of 35 patients on therapy had an RNA level >20,000 copies/mL. Nucleoside-resistance mutations were observed in 21 (68%) of 31 nucleoside-experienced subjects. Protease mutations necessary for high-level protease inhibitor (PI) resistance were present together with permissive mutations in 3 of 10 PI-experienced patients. Inability to identify high-risk individuals and to detect virologic failure may limit the effectiveness of antiretroviral drug programs and may promote the spread of drug resistance where virologic and immunologic monitoring are not available.
引用
收藏
页码:1259 / 1263
页数:5
相关论文
共 15 条
[1]  
[Anonymous], 1992, MMWR-MORBID MORTAL W, V41, P1
[2]  
BRINCHMANN JE, 1988, CLIN EXP IMMUNOL, V71, P182
[3]   HIV POPULATION-DYNAMICS IN-VIVO - IMPLICATIONS FOR GENETIC-VARIATION, PATHOGENESIS, AND THERAPY [J].
COFFIN, JM .
SCIENCE, 1995, 267 (5197) :483-489
[4]   Resistance of HIV-1 to antiretroviral agents in blood and seminal plasma: implications for transmission [J].
Eron, JJ ;
Vernazza, PL ;
Johnston, DM ;
Seillier-Moiseiwitsch, S ;
Alcorn, TM ;
Fiscus, SA ;
Cohen, MS .
AIDS, 1998, 12 (15) :F181-F189
[5]   Sexual transmission of an HIV-1 variant resistant to multiple reverse-transcriptase and protease inhibitors [J].
Hecht, FM ;
Grant, RM ;
Petropoulos, CJ ;
Dillon, B ;
Chesney, MA ;
Tian, H ;
Hellmann, NS ;
Bandrapalli, NI ;
Digilio, L ;
Branson, B ;
Kahn, JO .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (05) :307-311
[6]   Transmission of human immunodeficiency virus type 1 resistant to nevirapine and zidovudine [J].
Imrie, A ;
Beveridge, A ;
Genn, W ;
Vizzard, J ;
Cooper, DA .
JOURNAL OF INFECTIOUS DISEASES, 1997, 175 (06) :1502-1506
[7]   The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter [J].
Katzenstein, DA ;
Hammer, SM ;
Hughes, MD ;
Gundacker, H ;
Jackson, JB ;
Fiscus, S ;
Rasheed, S ;
Elbeik, T ;
Reichman, R ;
Japour, A ;
Merigan, TC ;
Hirsch, MS .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (15) :1091-1098
[8]   Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays [J].
Kozal, MJ ;
Shah, N ;
Shen, NP ;
Yang, R ;
Fucini, R ;
Merigan, TC ;
Richman, DD ;
Morris, D ;
Hubbell, ER ;
Chee, M ;
Gingeras, TR .
NATURE MEDICINE, 1996, 2 (07) :753-759
[9]  
LCARPENTER CC, 1998, JAMA-J AM MED ASSOC, V280, P78
[10]   In vivo sequence diversity of the protease of human immunodeficiency virus type 1: Presence of protease inhibitor-resistant variants in untreated subjects [J].
Lech, WJ ;
Wang, G ;
Yang, YL ;
Chee, Y ;
Dorman, K ;
McCrae, D ;
Lazzeroni, LC ;
Erickson, JW ;
Sinsheimer, JS ;
Kaplan, AH .
JOURNAL OF VIROLOGY, 1996, 70 (03) :2038-2043