Danner S, van Leeuwen R, Katlama C, Ingrand D, Weber J, Kitchen V; International Conference on AIDS.
Int Conf AIDS. 1993 Jun 6-11; 9: 477 (abstract no. PO-B26-2054).
Academic Medical Centre, Amsterdam.
This phase I/II dose escalation study was initiated in August 1991 to determine the safety, pharmacokinetics and preliminary activity of 3TC, the (-) enantiomer of 2'-deoxy-3'-thiacytidine (BCH189), in HIV positive, asymptomatic or mild ARC patients with a screening CD4 count < or = 400/mm3. 15 patients have been enrolled successively to each of 6 dose levels of 3TC, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0mg/kg/day, administered po BID (n = 90). Patients were assessed at weeks 1, 2, 4, 6, 8 and then at 4 week intervals for analyses of CD4 count, p24 antigenaemia, neopterin and beta 2 microglobulin levels, clinical measurements and safety assessments. Viral load was assessed in a subset of patients, by determination of levels of cellular viraemia at 0, 4 and 24 weeks of therapy. Retrospective analyses for all patients, of p24 antigenaemia after acid hydrolysis and determination of viral load by RNA-PCR were also carried out. Analysis showed reductions in viral load as measured by RNA-PCR. In addition, there were clear reductions in cellular viraemia in patients receiving 3TC at doses of 4mg/kg and above. Follow-up to date has revealed no significant drug related toxicity. The most frequent minor adverse events assessed as possibly drug related were intermittent headache (10%), fatigue (8%) and diarrhoea (7%). Transient rises of CD4 counts, and reductions of p24 antigen, serum neopterin and beta 2 microglobulin have been observed, although no dose-response relationship has been discerned in the surrogate markers studied. A cohort of 14 patients has now been enrolled at a dose of 20mg/kg, a similar pattern of results is emerging but analysis is as yet incomplete. Follow-up of clinical efficacy and safety continues in this study and further studies with 3TC are planned to start in 1993.
Publication Types:
Keywords:
- AIDS-Related Complex
- CD4 Lymphocyte Count
- Disease Progression
- HIV Infections
- HIV Seropositivity
- Humans
- Lamivudine
- Neopterin
- Viral Load
- Viremia
- beta 2-Microglobulin
Other ID:
UI: 102205038
From Meeting Abstracts