دورية
Origin of Human Immunodeficiency Virus Type 1 Quasispecies Emerging after Antiretroviral Treatment Interruption in Patients with Therapeutic Failure
| العنوان: | Origin of Human Immunodeficiency Virus Type 1 Quasispecies Emerging after Antiretroviral Treatment Interruption in Patients with Therapeutic Failure |
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| المؤلفون: | Kijak, Gustavo H., Simon, Viviana, Balfe, Peter, Vanderhoeven, Jeroen, Pampuro, Sandra E., Zala, Carlos, Ochoa, Claudia, Cahn, Pedro, Markowitz, Martin, Salomon, Horacio |
| المصدر: | The Journal of Virology; July 2002, Vol. 76 Issue: 14 p7000-7009, 10p |
| مستخلص: | ABSTRACTThe emergence of antiretroviral (ARV) drug-resistant human immunodeficiency virus type 1 (HIV-1) quasispecies is a major cause of treatment failure. These variants are usually replaced by drug-sensitive ones when the selective pressure of the drugs is removed, as the former have reduced fitness in a drug-free environment. This was the rationale for the design of structured ARV treatment interruption (STI) studies for the management of HIV-1 patients with treatment failure. We have studied the origin of drug-sensitive HIV-1 quasispecies emerging after STI in patients with treatment failure due to ARV drug resistance. Plasma and peripheral blood mononuclear cell samples were obtained the day of treatment interruption (day 0) and 30 and 60 days afterwards. HIV-1 poland envwere partially amplified, cloned, and sequenced. At day 60 drug-resistant variants were replaced by completely or partially sensitive quasispecies. Phylogenetic analyses of polrevealed that drug-sensitive variants emerging after STI were not related to their immediate temporal ancestors but formed a separate cluster, demonstrating that STI leads to the recrudescence and reemergence of a sequestrated viral population rather than leading to the back mutation of drug-resistant forms. No evidence for concomitant changes in viral tropism was seen, as deduced from envsequences. This study demonstrates the important role that the reemergence of quasispecies plays in HIV-1 population dynamics and points out the difficulties that may be found when recycling ARV therapies with patients with treatment failure. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 0022538X 10985514 |
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| DOI: | 10.1128/JVI.76.14.7000-7009.2002 |