Third International Congress Drug Therapy in HIV Infection 3-7 November 1996 Glasgow, UK

THE SAFETY AND ANTIVIRAL EFFECT OF 1592U89, ALONE AND IN COMBINATION WITH ZIDOVUDINE IN HIV-1 INFECTED PATIENTS WITH CD4+ COUNTS 200-500 CELLS/MM³

A. Sonnerborg¹, D. Lancaster², R. Torres³, M. Thompson⁴, M. Saag⁵, R. Schooley⁶, J. Mulder⁷, B. Gazzard⁸, R. D'Aquilla⁹, M. Gurgui¹⁰, J. Feinberg¹¹, M. Santin¹², W. Lang¹³, P.R. Harrigan¹⁴, H. Steel¹⁴, S. Tortell¹⁴, C. Romero^14
1Huddinge Hosp., ²Methodist Hosp., ³St. Vincent's, ⁴ARCA, ⁵Univ. of Alabama, ⁶Univ. of Colorado, ⁷Slotervaartzienkenhuis, ⁸Chelsea & Westminster, ⁹MGH, ¹⁰San Pablo Hosp., ¹¹Univ. of Cinncinnati, ¹²Bellvitge Hosp., ¹³VirRx Inc., ¹⁴Glaxo Wellcome

Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP4.1
AIDS 1996, Vol. 10 (Suppl. 2);S12

The objective of protocol 131-002 (CNAA 2001) was to determine the safety, pharmacokinetics and preliminary antiviral effect of the novel HIV-1 RT inhibitor 1592U89, alone and in combination with Zidovudine (ZDV) in HIV-1 infected adults.

Subjects with limited prior antiretroviral exposure (≤ 12 weeks ZDV therapy), who did not have AIDS; and with a CD4+ cell count between 200-500 cells/mm³, were screened and sequentially assigned to one of four dose escalating treatment groups. Four weeks of 1592U89 monotherapy were followed by 8 weeks of randomized combination therapy with either 1592U89/ZDV or 1592U89/ZDV-placebo. Subjects were followed for an additional 4 weeks post-treatment. HIV-1 virologic and immunologic responses to 1592U89 were assessed by quantitative HIV-RNA PCR and CD4+ cell counts, respectively. Safety was assessed by changes in laboratory parameters and adverse experience reporting.

Preliminary blinded data indicate that 1592U89 both as monotherapy and in combination with ZDV, elicit a marked and sustained reduction in viral load over 12 weeks. Corresponding CD4+ cell rises were also observed.

Both 1592U89 monotherapy and the combination with ZDV were well tolerated. Most common adverse events included nausea, headache, asthenia, and rash. Unblinded data on all four cohorts will be presented.

The extent of viral suppression and immunologic response observed with 1592U89 alone and in combination with ZDV, categorises 1592U89 as a highly potent nucleoside analogue, which together with the safety profile, merits further investigation.

Presenting author: A. Sonnerborg

1996-11-03
OP4.1

Originally published in AIDS Volume 10, Supplement 2 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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