Human immunodeficiency virus type 1 protease genotypes and in vitro protease inhibitor susceptibilities of isolates from individuals who were switched to other protease inhibitors after long-term saquinavir treatment

被引:91
作者
Winters, MA [1 ]
Schapiro, JM [1 ]
Lawrence, J [1 ]
Merigan, TC [1 ]
机构
[1] Stanford Univ, Ctr AIDS Res, Stanford, CA 94305 USA
关键词
D O I
10.1128/JVI.72.6.5303-5306.1998
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
An understanding of the mechanisms of virologic cross-resistance between human immunodeficiency virus type 1 protease inhibitors is important for the establishment of effective treatment strategies for patients who no longer respond to their initial protease inhibitor. Protease gene sequencing results from patients treated with saquinavir showed significant increases in the frequency of the G48V protease mutation in patients receiving higher doses of the drug. In addition, all six patients who developed the G48V mutation during saquinavir therapy developed the V82A mutation either on continued saquinavir or after a switch to nelfinavir or indinavir. In vitro susceptibility assays showed that all 13 isolates with reduced susceptibilities to two or more protease inhibitors had either the G48V or L90M mutation, along with an average of six other protease mutations. Reduced susceptibility to nelfinavir was found in 14 isolates, but only 1 possessed the D30N mutation. These results suggest that mutations selected in vivo by initial saquinavir therapy may provide more cross-resistance to the other protease inhibitors than has been previously reported.
引用
收藏
页码:5303 / 5306
页数:4
相关论文
共 22 条
[1]  
*AIDS CLIN TRIALS, 1997, VIR MAN HIV LAB
[2]  
Boucher C, 1996, AIDS, V10, pS15
[3]   Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor [J].
Condra, JH ;
Holder, DJ ;
Schleif, WA ;
Blahy, OM ;
Danovich, RM ;
Gabryelski, LJ ;
Graham, DJ ;
Laird, D ;
Quintero, JC ;
Rhodes, A ;
Robbins, HL ;
Roth, E ;
Shivaprakash, M ;
Yang, T ;
Chodakewitz, JA ;
Deutsch, PJ ;
Leavitt, RY ;
Massari, FE ;
Mellors, JW ;
Squires, KE ;
Steigbigel, RT ;
Teppler, H ;
Emini, EA .
JOURNAL OF VIROLOGY, 1996, 70 (12) :8270-8276
[4]   IN-VIVO EMERGENCE OF HIV-1 VARIANTS RESISTANT TO MULTIPLE PROTEASE INHIBITORS [J].
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 .
NATURE, 1995, 374 (6522) :569-571
[5]   HIV-1 protease inhibitors - A review for clinicians [J].
Deeks, SG ;
Smith, M ;
Holodniy, M ;
Kahn, JO .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1997, 277 (02) :145-153
[6]  
DULIOUST A, 1997, INT WORKSH HIV DRUG
[7]  
EASTMAN PS, 1997, INT WORKSH HIV DRUG
[8]   In vivo resistance to a human immunodeficiency virus type 1 proteinase inhibitor: Mutations, kinetics, and frequencies [J].
Jacobsen, H ;
Hanggi, M ;
Ott, M ;
Duncan, IB ;
Owen, S ;
Andreoni, M ;
Vella, S ;
Mous, J .
JOURNAL OF INFECTIOUS DISEASES, 1996, 173 (06) :1379-1387
[9]  
KEMPF D, 1997, INT WORKSH HIV DRUG
[10]   Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir [J].
Kempf, DJ ;
Marsh, KC ;
Kumar, G ;
Rodrigues, AD ;
Denissen, JF ;
McDonald, E ;
Kukulka, MJ ;
Hsu, A ;
Granneman, GR ;
Baroldi, PA ;
Sun, E ;
Pizzuti, D ;
Plattner, JJ ;
Norbeck, DW ;
Leonard, JM .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (03) :654-660