Second International Congress Drug Therapy in HIV Infection 18-22 November 1994 Glasgow, UK

THE PREDICTION OF CLINICAL EFFECT AND RATE OF RESISTANCE DEVELOPMENT FROM CELL CULTURE AND ANIMAL EXPERIMENTS WITH ANTI-HIV DRUGS

Bo Öberg^1,2, Disa Bottiger² and Lotta Yrang^1
1 Medivir AB, Huddinge, Sweden, ² MTC, Karolinska InstilUte, Stockholm, Sweden.

Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 5.2
AIDS 1994, Vol. 8 (Suppl. 4);S4

The development of drugs against HIV/AIDS has revealed that there is often a lack of correspondence between activity against HIV in cell culture and clinical effect. Furthermore, clinical trials have shown that resistance development is a major obstacle in designing useful drugs against HIV/AIDS. It is therefore important early in the development to be able to select those compounds likely to be active in vivo and to result, at least, in a slow development of resistance.

Cell culture methods are now available where the respective rate of resistance for several compounds correspond to the rates found in clinical trials. These cell culture assays also reveal the same mutations in HIV reverse transcriptase and proteinase as found clinically with inhibitors directed to these enzymes.

Infection of cynomolgus monkeys with SIV and HIV-2 give infections very similar to that at HIV-1 in humans and in the case of SIV a similar pathogenesis. The antiviral effect of AZT, ddI, ddC, d4T, PFA, FLT and other compounds have been evaluated in SIV and HIV-2-infected monkeys. There is a better correspondence between the antiviral effects in monkeys and man than between the effects in cell cultures and man. By a combination of cell culture assays determining the rate of resistance development and efficacy studies in SIV and HIV-2-infected monkeys it appears possible today to make good predictions on clinical antiviral effect and risk for resistance development of anti-HIV drugs.

1994-11-18
5.2

Originally published in AIDS Volume 8, Supplement 4 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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