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

EFFICACY AND TOXICITIES OF COMBINATION ANTIRETROVIRAL THERAPIES

Margaret A. Fischl, M.D.
University of Miami School of Medicine, Miami, Florida. USA.

Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 7.2
AIDS 1994, Vol. 8 (Suppl. 4);S6

Phase II data suggest that combination therapies with nucleoside analogues, zidovudine and either zalcitabine or didanosine, result in a greater increase in CD4 cell counts which is sustained longer than that seen with monotherapy. Similar findings have been noted with plasma HIV RNA and quantitative microculture. However, the development of at least zidovudine resistance appears unchanged with the co-administration of either didanosine or zalcitabine. Preliminary in vitro data suggest that the combination of zidovudine and stavudine (d4T) is additive to synergistic and should be explored in early clinical trials.

In addition, the co-administration of zidovudine with several non-nucleoside reverse transcriptase inhibitors, nevirapine. atevirdine, and delavirdine appears to result in more pronounced effects and may delay the onset of non-nucleoside RT inhibitor drug resistance.

Several studies have also evaluated triple combination therapy. Triple combination therapy with zidovudine, zalcitabine and interferon .-2a did not result in enhanced CD4 cell effects or antiviral effects as measured by either serum p24 antigen levels or plasma HIV RNA. The toxicity of this triple combination therapy was greater than' combination therapy with zidovudine and zalcitabine. However, preliminary data suggest more prominent effects on CD4 cell counts and viral burden for other triple combination therapies involving nucleosides, non-nucleoside RT inhibitors or protease inhibitors.

These data would suggest the need for further evaluation of combination therapies for the treatment of all stages of HIV disease. The possibilities of combining drugs that effect different sites of HIV replication exists and include combinations of nucleoside analogues and either protease inhibitors or glycosylation inhibitors.

Presenting author: Margaret A. Fischl, M.D.

1994-11-18
7.2

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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