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

RESEARCH IN THE POST LICENSING SITUATION

Merigan, T.C.
Stanford University School of Medicine, Center for AIDS Research, 300 Pasteur Drive, Room S-156, Stanford, CA 94305-5107

Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 3.4
AIDS 1996, Vol. 10 (Suppl. 2);S3

Potent and prolonged action of drugs have been shown in monotherapy or combinations on HIV plasma RNA and CD4 cell levels in a number of settings which, in turn, are the best markers in predicting subsequent disease course. Because of the acute pandemic, HIV drugs in the U.S. have been licensed primarily due to their immediate affects on such perimeters. These studies generally are of less than one year duration whereas physicians must maintain effective drug action in patients for decades. This means that regulatory bodies must be directed to require more post licensing studies to allow informed use of drugs over long periods of time. As HIV therapy efforts matures, the algorithms for such studies become more clear. Furthermore, the fact that 2 major pharmaceutical manufacturers will be replacing their original antiretroviral formulation with new ones in the coming year clearly demonstrates that they have been developed extremely rapidly without the usual step by step optimization afforded other agents.

Optimistic scenarios have recently suggested to some that after long term suppressive therapy, viral infection may be eradicated so that patients can stop therapy and the virus will not reappear in the circulation. Reasoning from other chronic viral infection treatment settings (such as herpes and hepatitis viruses) where immune control is more intact and occasionally successful on its own in suppressing the virus, it seems likely that we will see HIV infection reoccur. Therefore, I believe we will need lifelong therapy of the HIV infected.

We need intense study of more long term combinations especially at the virologic level and better rationales are needed for moving between combinations. It is imperative in planning all such strategy trials that the right information is obtained during phase 1/2 studies regarding the pathways for escape from drug action. For example, careful studies of tissue virus, drug resistance mechanisms and long term compliance and drug metabolism are needed. We must be sure that all treated phase 1,2 and 3 patients continue treatment as long as reasonable and all relevant viral, drug, and host perimeters are monitored from the first treated patient on. We must have this information to rationally employ any agent in phase 4 trials in combination efforts with additional agents as they become available. Ultimately such information is mandatory for the most innovative practice of medicine and realizing the full potential of any given antiviral agent for patients.

Presenting author:

1996-11-03
3.4

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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