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

CHARACTERISATION OF HIV DRUG SENSITIVITY DURING ANTIRETROVIRAL TREATMENT WITH A PROTEASE INHIBITOR (RO 31.8959 - SAQUINAVIR) ALONE OR IN COMBINATION WITH ZIDOVUDINE.

Andreoni Massimo, L. Ercoli, L Sarmati, §J. Mous, @ K. Bragman, #I. Duncan, *G. Giannini, *C. Galluzzo, *S. Vella
Infectious Diseases, University of Rome "Tor Vergata", Italy, §F.Hoffmann-La Roche, PRTB, Basel, Switzerland, @Roche International Clinical Research Center, Strasbourg,France,# RocheProducts,Dept. of Biology, WelwynGarden, UK, 'Laboratory of Virology,IstitllloSuperioredi Sanita, Rome, Italy.

Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 5.7
AIDS 1994, Vol. 8 (Suppl. 4);S5

HIV strains were isolated from about 30 previously untreated patients with advanced HIV disease (CD4 < 300/mm³), before and after 16 weeks of therapy with Ro 31-8959 alone, AZT alone, and with three different combined regimens of the two drugs. HIV strains were also isolated from patients treated for 18 months with the combination of the two drugs. Viral isolates derived from PBMC and/or plasma culture were tested for changes in drug sensitivity by measuring growth in donor PBMC in the presence of different concentrations of R031-8959 (0,01-100 nM) or of AZT (0,001-5 μM).

Only a few strains isolated at week 16, from patients treated with R031- 8959 monotherapy, showed some degree of drug resistance (IC₅₀ range: 11-39 nM ). The isolation of resistant strains correlated with the presence of high base-line levels of viral replication, as determined by plasma viremia titration and HIV-RNA PCR technique. The genotype of the isolated strains showed the same pattern of codon mutations of R031-8959 resistant strains selected in vitro. No HIV resistant strains' were found among the isolates obtained after 16 weeks of combined regimen, although some of the viral strains isolated after 18 months of combined treatment were resistant to R031-8959 (IC₅₀ range: 18-67 nM). The usual pattern of drug.resistance to AZT seems to be modified after AZT/Ro 31-8959 combination therapy.

The preliminary data regarding the pattern of reduced sensitivity to Ro 31-8959 suggest that drug resistance may not be a major problem in the management of patients with this protease inhibitor.

Presenting author: Andreoni Massimo

1994-11-18
5.7

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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