Phase I/II study of 3TC (lamivudine) in HIV-positive, asymptomatic or mild AIDS-related complex patients: sustained reduction in viral markers. The Lamivudine European HIV Working Group.
OBJECTIVE
To evaluate the efficacy of 3TC (lamivudine), a synthetic nucleoside analogue that inhibits HIV reverse transcriptase in vitro, as treatment for HIV-positive, asymptomatic or mild AIDS-related complex patients.


METHODS
Open-label, multinational and multicentre, non-comparative, escalating dose study.


METHODS
Patients who meet the selection criteria (n = 104) were enrolled in three European countries. Ten to 15 patients were included at each of the six dose levels of 3TC (0.5, 1.0, 2.0, 4.0, 8.0, 12.0 and 20.0 mg/kg daily in two divided doses every 12 h). Virological parameters--immune-complex dissociation (ICD) assay for HIV p24 antigenaemia, plasma HIV RNA load, whole blood assay and cellular viraemia--were evaluated at weeks 0, 4, 12 and 24.


RESULTS
Sustained reductions in HIV RNA load and in ICD p24 antigen levels were observed and maintained over the 12-week assessment period. Greater reductions were noted at higher doses but this trend did not reach statistical significance. In 38 patients, reductions of cell viraemia were significantly greater at 4 weeks for patients treated at higher doses of 3TC.


CONCLUSIONS
These virological data show that 3TC is a potent inhibitor of HIV replication in HIV-positive, asymptomatic or mild ARC patients as assessed by ICD p24 antigenaemia, plasma HIV RNA load and cell viraemia.
Ingrand
D
D
Department of Medical Virology, Pitié-Salpétrière Hospital, Paris, France.
Weber
J
J
Boucher
C A
CA
Loveday
C
C
Robert
C
C
Hill
A
A
Cammack
N
N
D000386:AIDS-Related Complex / Q000097:blood / Q000188:drug therapy; D000328:Adult; D000936:Antigen-Antibody Complex / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000187:drug effects; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006679:HIV Seropositivity / Q000097:blood / Q000188:drug therapy; D006801:Humans; D019259:Lamivudine; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D016133:Polymerase Chain Reaction; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D014766:Viremia; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000936:Antigen-Antibody Complex; D000998:Antiviral Agents; D016655:HIV Core Protein p24; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D016047:Zalcitabine