Rapid changes in human immunodeficiency virus type 1 RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC).
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 (approximately 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.
Schuurman
R
R
Antiviral Therapy Laboratory (Department of Virology), University of Amsterdam, Academic Medical Centre, Netherlands.
Nijhuis
M
M
van Leeuwen
R
R
Schipper
P
P
de Jong
D
D
Collis
P
P
Danner
S A
SA
Mulder
J
J
Loveday
C
C
Christopherson
C
C
D018791:CD4 Lymphocyte Count; D004352:Drug Resistance, Microbial; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy* / Q000382:microbiology; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019259:Lamivudine; D008137:Longitudinal Studies; D008297:Male; D012367:RNA, Viral / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D016655:HIV Core Protein p24; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D016047:Zalcitabine; D054303:HIV Reverse Transcriptase