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 change s in codon 184, causing high-level resistance to lamivudine, were dete rmined in longitudinal serum samples from HIV-1 p24 antigen-positive a nd -negative patients. A marked decline in the amount of HIV-1 RNA (si milar to 95% below baseline) and HIV-1 p24 antigen was observed within 2 weeks, followed by a rise that coincided with the appearance of lam ivudine-resistant viruses in serum (isoleucine mutants initially, whic h were subsequently replaced by valine variants). After 12 weeks, a pa rtial 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 i ncrease in viral RNA load.