RAPID CHANGES IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RNA LOAD AND APPEARANCE OF DRUG-RESISTANT VIRUS POPULATIONS IN PERSONS TREATED WITH LAMIVUDINE (3TC)

被引：434

作者：

SCHUURMAN, R

NIJHUIS, M

VANLEEUWEN, R

SCHIPPER, P

DEJONG, D

COLLIS, P

DANNER, SA

MULDER, J

LOVEDAY, C

CHRISTOPHERSON, C

KWOK, S

SNINSKY, J

BOUCHER, CAB

机构：

[1] UNIV AMSTERDAM, ACAD MED CTR,NATL AIDS THERAPY EVALUAT CTR, DEPT VIROL,ANTIVIRAL THERAPY LAB, 1105 AZ AMSTERDAM, NETHERLANDS

[2] UNIV AMSTERDAM, ACAD MED CTR, DEPT INTERNAL MED, 1105 AZ AMSTERDAM, NETHERLANDS

[3] GLAXO RES & DEV LTD, GREENFORD, MIDDX, ENGLAND

[4] UCL, SCH MED, DIV VIROL, LONDON W1N 8AA, ENGLAND

[5] ROCHE MOLEC SYST, DEPT INFECT DIS, ALAMEDA, CA USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 1995年 / 171卷 / 06期

关键词：

D O I：

10.1093/infdis/171.6.1411

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The effect of the appearance of drug-resistant human immunodeficiency virus type 1 (HIV-1) on viral RNA load was studied in patients treated with the reverse transcriptase inhibitor lamivudine. During the first 12 weeks of treatment, HIV-1 RNA concentrations and amino acid changes in codon 184, causing high-level resistance to lamivudine, were determined in longitudinal serum samples from HIV-1 p24 antigen-positive and -negative patients. A marked decline in the amount of HIV-1 RNA (similar to 95% below baseline) and HIV-1 p24 antigen was observed within 2 weeks, followed by a rise that coincided with the appearance of lamivudine-resistant viruses in serum (isoleucine mutants initially, which were subsequently replaced by valine variants). After 12 weeks, a partial antiviral effect was observed despite the presence of a complete codon 184 mutant virus population in serum. This study shows that the rapid appearance of drug-resistant virus in serum is followed by an increase in viral RNA load.

引用

页码：1411 / 1419

页数：9

共 27 条

[1] Larder B.A., Darby G., Richman D.D., Hiv with reduced sensitivity to zidovudine (Azt) isolated during prolonged therapy, Science, 243, pp. 1731-1734, (1989)
[2] Rooke R., Tremblay M., Soudeyns H., Et al., Isolation of drug-resistant variants of hiv-1 from patients on long-term zidovudine therapy, AIDS, 3, pp. 411-415, (1989)
[3] Fitzgibbon J.E., Howell R.M., Haberzettl C.A., Sperber S.J., Gocke D.J., Dubin D.T., Human immunodeficiency virus type i poi gene mutations which cause decreased susceptibility to 2',3'-dideoxycytidine, Antimicrob Agents Chemother, 36, pp. 153-157, (1992)
[4] Saag M.S., Emini E.A., Laskin O.L., Et al., L-697 6w. A short-term clinical evaluation of l-697,661. A non-nucleoside inhibitor of hiv-1 reverse transcriptase, N Engl J Med, 329, pp. 1065-1072, (1993)
[5] St. Clair M.H., Martin J.L., Tudor-Williams G., Et al., Resistance to ddl and sensitivity to azt induced by a mutation in hiv-1 reverse transcriptas, Scienc, 25, (1991)
[6] De Jong M.D., Loewenthal M., Boucher C., Et al., Alternating nevira pine and zidovudine treatment of human immunodeficiency virus type 1 -infected persons does not prolong nevirapine activity, J Infect Dis, 169, pp. 1346-1350, (1994)
[7] Richman, Havlir D.D., Corbeil D.J., Et al., Nevirapine resistance mutations of human immunodeficiency virus type i selected during therapy, J Virol, 68, pp. 1660-1666, (1994)
[8] Gao Q., Gu Z., Hiscott J., Dionne G., Wainberg M.A., Generation of drug-resistant variants of human immunodeficiency virus type 1 by in vitro passage in increasing concentrations of 2',3'-dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine, Antimicrob Agents Chemother, 37, pp. 130-133, (1993)
[9] Schinazi R.F., Lloyd R.M., Nguyen M.H., Et al., Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleoside, Antimicrob Agents Chemothe, 3, pp. 875-878, (1993)
[10] Tisdale M., Kemp S.D., Parry N.R., Larder B.A., Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the ymdd region of reverse transcriptase, Proc Natl Acad Sci USA, 90, pp. 5653-5656, (1993)

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