Moyle GJ, Youle M, Higgs C, Monaghan J, Peterkin J, Chapman S, Nelson M; International Conference on AIDS.
Int Conf AIDS. 1996 Jul 7-12; 11: 18 (abstract no. Mo.B.173).
Kobter Centre, Chelsea And Westminister Hospital, London, UK. Fax: UK 171 938 3460.
Introduction: In the first 28 day open-label phase I/II dose escalation trial with AG1343, HIV-positive therapy naive persons, with baseline CD4 200-500 cells/mm3 and viral loads greater than or equal to 20000 copies/ml (by bDNA) were treated with doses of 771 (N=10) and 1026 mg (base equivalent)/day (N=10) of AG1343 [1]. Patients with a greater than or equal log reduction in viral load at day 28 were offered continued AG1343. Objective. To assess the extended (greater than 28 days) safety, virologic and immunologic activity of AG1343 in initial virological responders and safety of AG1343 when given with nucleoside analogues. Methodology: Virologic responders were offered continued AG1343 at their initial dose until safety was established at higher doses. The current dose being 1200 mg/day. Patients were assessed monthly for clinical events, CD4 cell count and viral load by bDNA. Patients were offered the opportunity to receive additional nucleoside analogue therapy, at the physicians' discretion. Results. Six patients entered the extension phase. Patients have been followed for 5-8 months. To date (Jan 1996) 3 patients have added additional nucleoside analogue therapy (all with zidovudine 5-600 mg/day and zalcitabine 2.25 mg/day) due to virological failure as evidenced by return of viral load to baseline or worse. Nucleosides were added at month 3 or 4 in these patients, prompting falls in viral load of 0.5, 1.2, and 1.8 log. The 3 patients remaining on AG1343 monotherapy have viral loads at 2.3, 0.67, 0.16 below baseline at months 7, 8, and 6, respectively. CD4 cell counts remain at or above baseline in all patients. No serious adverse events or disease progressions have occurred. Adverse events reported include loose stools, poor concentration, intermittent headaches, and moderate hypertension. No unexpected adverse events have been reported in patients receiving concomitant nucleoside analogues. Conclusions. AG1343 may be safely administered for prolonged periods and with nucleoside analogues. Patients with large initial virological reductions may have prolonged responses to AG1343.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- CD4 Lymphocyte Count
- Clinical Trials, Phase I as Topic
- HIV
- HIV Infections
- HIV Protease Inhibitors
- HIV Seropositivity
- Humans
- Nelfinavir
- Safety
- Viral Load
- Zalcitabine
- Zidovudine
Other ID:
UI: 102216792
From Meeting Abstracts