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

[21] Hughes M.D., Stein D.S., Gundacker H.M., Valentine F.T., Phair J.P., Vol-Berding P.A., Within-subject variation in cd4 lymphocyte count in asymptomatic human immunodeficiency virus infection: Implications for patient monitoring, J Infect Dis, 169, pp. 28-36, (1994)
[22] Schuurman R., Keulen W., Modified protocol for dna sequence analysis using sequenase 2.0, Biotechniques, 11, (1990)
[23] Gao Q., Gu Z., Parniak M.A., Et al., The same mutation that encodes low-level human immunodeficiency virus type 1 resistance to 2',3'- dideoxyinosine and 2',3'-dideoxycytidine confers high-level resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine, Antimi- Crob Agents Chemother, 37, pp. 1390-1392, (1993)
[24] Ji J., Loeb L.A., Fidelity of hiv-1 reverse transcriptase copying a hyper variable region of the hiv-1 env gene, Virology, 199, pp. 323-330, (1994)
[25] Wakefield J.K., Jablonski S.A., Morrow C.D., In vitro enzymatic activity of human immunodeficiency virus type 1 reverse transcriptase mutants in the highly conserved ymdd amino acid motif correlates with the infectious potential of the proviral genome, J Virol, 66, pp. 6806-6812, (1992)
[26] Larder B.A., Kemp S.D., Purifoy D., Infectious potential of human immunodeficiency virus type 1 reverse transcriptase mutants with altered inhibitor sensitivity, Proc Natl Acad Sci USA, 86, pp. 4803-4807, (1989)
[27] Boyer P.L., Ferris A.L., Hughes S.H., Cassette mutagenesis of the reverse transcriptase of human immunodeficiency virus type i, J Virol, 66, pp. 1031-1039, (1992)

← 1 2 3 →