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

OUTSTANDING ISSUES IN THE INVESTIGATION OF ANTIRETROVIRAL CHEMOTHERAPY

Robert T. Schooley
University of Colorado, Denver

Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 1.2
AIDS 1996, Vol. 10 (Suppl. 2);S1

In the decades since the introduction of zidovudine much progress has been made in the development of antiretroviral chemotherapeutic agents and in approaches to their use. Initial studies were hampered by the absence of tools to access either the underlying rates of viral replication or the effects of antiviral chemotherapeutic agents on this replication rate. This limitation led to both an overestimation of the potency of available agents as antimicrobial agents and thus, to inappropriate optimism with respect to the magnitude and durability of the effects of these agents. Most antiretroviral chemotherapy trials were designed to compare fixed drugs or drug regimens for relatively short periods in defined patient populations with the expectation that specific regimens would emerge that were superior in defined patient populations.

With the advent of more sensitive and accurate tools for the assessment viral replication in vivo, several important principles have emerged:

1. Limitations in the magnitude and durability of the clinical effects of prior antiretroviral chemotherapeutic attempts can be attributed to a large extent to the incomplete control of viral replication associated with these regiments.

2. More potent and durable retroviral regimens are associated with more substantial and prolonged immunologic and clinical benefits.

3. In general, agents or regimens with comparable antiviral effects manifest similar clinical effects.

Research focused on antiretroviral chemotherapy has evolved from a search for specific regimens that may be clinically superior to the elucidation of strategies that afford the ability to suppress viral replication maximally for a prolonged duration with the least associated toxicity in individual patients. Thus, as in clinical practice, the emphasis in clinical trials is in the process of shifting from fixed drugs and regimens to flexible combinations of drugs that may be adjusted to provide targeted antiretroviral effects for prolonged durations. The major questions that remain include how best to accomplish this, how to maximize the accompanying immune reconstitution, what implications such antiviral and immune reconstituting effects have for primary and secondary prophylactic strategies for opportunistic infections, and whether virus can be eliminated from infected individuals.

Presenting author: Robert T. Schooley

1996-11-03
1.2

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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