Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients.
The nonnucleoside reverse transcriptase inhibitor nevirapine rapidly selects for mutant human immunodeficiency virus (HIV) in vivo. The most common mutation occurs at amino acid residue 181 in patients receiving monotherapy. After the initiation of nevirapine therapy, plasma and peripheral blood mononuclear cell samples were collected at frequent intervals and assayed for HIV RNA levels and the proportion of virus containing a mutation at residue 181. HIV RNA levels remained stable for the first 24 h after initiation of therapy and rapidly declined between 1 and 7 days. There was a consistent maximum decrease of 2 log10 HIV RNA copies per ml of plasma (range, 1.96 to 2.43) from baseline after 2 weeks in all monotherapy subjects. The estimated median half-life of HIV RNA was 1.11 days (range, 0.63 to 1.61). After 14 days of therapy, HIV RNA levels began to increase and 181 mutant virus was detected. The estimated doubling time of the emerging virus population ranged from 1.80 to 5.73 days. Viral DNA in peripheral blood mononuclear cells turned over from wild type to the mutant with a mutation at residue 181 significantly more slowly than did HIV RNA in plasma. In two subjects, the calculated prevalence of the 181 mutant virus prior to treatment was 7 and 133 per 10,000 copies of plasma HIV RNA.
Department of Medicine, University of California, San Diego 92103, USA. dhavlir@ucsd.edu.
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Havlir
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Eastman
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Gamst
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Richman
D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015658:HIV Infections / Q000821:virology*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D009154:Mutation; D019829:Nevirapine; D011725:Pyridines / Q000494:pharmacology*; D012367:RNA, Viral / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014779:Virus Replication
D011725:Pyridines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine