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| IN-VIVO EMERGENCE OF HIV-1 VARIANTS RESISTANT TO MULTIPLE PROTEASE INHIBITORS |
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| Author(s): 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 |
| Source: NATURE Volume: 374 Issue: 6522 Pages: 569-571 Published: APR 6 1995 |
| Times Cited: 761 References: 28 |
| Abstract: INHIBITORS Of the human immunodeficiency virus type 1 (HIV-1) protease have entered clinical study as potential therapeutic agents for HIV-1 infection. The clinical efficacy of HIV-1 reverse transcriptase inhibitors has been limited bg the emergence of resistant viral variants. Similarly, variants expressing resistance to protease inhibitors have been derived in cell culture(1-10). We now report the characterization of resistant variants isolated from patients undergoing therapy with the protease inhibitor MX-639 (formerly designated L-735,524). Five of these variants, isolated from four patients, exhibited cross-resistance to all members of a panel of six structurally diverse protease inhibitors. This suggests that combination therapy with multiple protease inhibitors may not prevent loss of antiviral activity resulting from resistance selection. In addition, previous therapy with one compound may abrogate the benefit of subsequent treatment with a second inhibitor. |
| Document Type: Article |
| Language: English |
| Reprint Address: CONDRA, JH (reprint author), MERCK SHARP & DOHME LTD, RES LABS, DEPT ANTIVIRAL RES, W POINT, PA 19486 USA |
Addresses:
1. MERCK SHARP & DOHME LTD, RES LABS, DEPT CLIN PHARMACOL, W POINT, PA 19486 USA
2. THOMAS JEFFERSON UNIV, DIV INFECT DIS, PHILADELPHIA, PA 19107 USA
3. UNIV ALABAMA, DEPT MED, BIRMINGHAM, AL 35294 USA |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: QR069 |
| ISSN: 0028-0836 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |