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

WHEN TO START, AND WITH WHAT

G. Skowron
Division of Infectious Diseases, Roger Williams Hospital and Brown University School of Medicine, Providence, RI, USA

Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 12.3
AIDS 1996, Vol. 10 (Suppl. 2);S7

Various combinations of nucleoside analogues, non-nucleoside analogues and/or protease inhibitors have demonstrated potent antiretroviral effects at all stages of HIV disease. The duration of profound viral suppression and long-term clinical benefits of these therapies, however, is still under study.

Viral load measurements have demonstrated that early 'set points' predict subsequent clinical outcomes. Early and aggressive treatment to lower viral load might convert a poor prognosis into a better one, via several mechanisms. First, treatment at or around the time of seroconversion may lower the viral 'set point' Second, the emergence of drug-resistant virus might be slowed by reducing viral replication rates to undetectable levels. Third, beneficial cellular immune function may be preserved.

Several studies have suggested that combination treatment during primary infection reduces both viral load and early clinical events. Mathematical modeling predicts possible elimination of virus replicating in lymphocytes and macrophages within 1 1/2 to 3 years; the influence of sanctuary sites and eventual outgrowth of drug-resistant strains temper optimism for cure. Anecdotal reports, however, suggest that multi-drug therapy that results in undetectable levels of culturable virus and viral RNA in blood and lymph node does not prevent subsequent viral rebound after drug cessation.

The goal of early and aggressive drug therapy is to essentially halt viral replication; proposed therapeutic regimens are comprised of at least 3 drugs. Multiple combination of licensed, and soon-to-be licensed agents are available, yet most are untested in early (CD4 > 500) HIV disease. The promise of early therapy is supported by the increasing number of available agents with differing mechanisms of action, side effect profiles and patterns of cross-resistance.

Clinicians in daily practice are being asked to skillfully apply the abundant early, yet encouraging, data to individuals from first exposure, to seroconversion, to asymptomatic infection and more advanced disease. More rational approaches to early and aggressive treatment await a greater understanding of the pathogenesis of HIV disease and the results of additional clinical studies.

Presenting author: G. Skowron

1996-11-03
12.3

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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