Journal
VIROLOGY
Volume 338, Issue 1, Pages 1-8Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2005.05.008
Keywords
HIV-1; antiretroviral therapy; lethal mutagenesis
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Mutagenic treatments resulted in occasional, not systematic, human immunodeficiency virus type 1 (HIV-1) extinction. To study the possibility that a combination of an antiretroviral inhibitor, to reduce the viral replicative load, and a mutagenic agent could be more effective in producing viral extinction than a mutagenic agent alone, we have compared the efficiency of extinction of HIV-1 by the mutagenic deoxyribonucleoside analogue 5-hydroxydcoxycytidine (5-OHdC) alone and in combination with the HIV-1 nucleoside reverse transcriptase (RT) inhibitor AZT. Serial passages in peripheral mononuclear cells (PBMC) or MT-4 cells of primary HIV-1 isolates or HIV-1 NL4-3 in the presence of a single drug (AZT 0.01 mu M or 5-OHdC 2 mM) failed to systematically extinguish high fitness HIV-1 replication after 16 serial transfers. However, systematic extinction of HIV-1 was observed when a combination of the mutagenic agent 5-OHdC and AZT was used. These results demonstrate that combinations of mutagenic agents and antiretroviral inhibitors have the potential to drive HIV-1 into extinction. (C) 2005 Elsevier Inc. All rights reserved.
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