Fifth International Congress Drug Therapy in HIV Infection 22-26 October, 2000 Glasgow, UK

PLANNING FIRST LINE (AND THEREFORE SECOND LINE) THERAPY

S. Hammer
Columbia University, New York, USA

Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL1.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S1

The optimal strategic use of antiretroviral agents has become increasingly critical as the limitations of currently available drug regimens have been recognized. Further, as the options for potent initial regimens have expanded, the most critical decision in planning first-line therapy today is when is the appropriate time to begin treatment. Arguments in favor of earlier intervention include the potential for greater immune preservation and a higher likelihood of viral suppression. Arguments against include effects on quality of life, the risk of short-term and long-term toxicities, the ability to adequately restore protective immune function in most patients with mid- to later stage disease and the risk of development of drug resistance which may severely limit future treatment options. Although published guidelines assist clinicians and patients with the decision on when to start therapy, it should be recognized that no definitive, prospective, clinical trial data exist which answer this question. There is consensus that all symptomatic patients should be treated. For asymptomatic patients for whom the initial decision is to defer therapy, this should be reconsidered as the CD4 cell count falls below 350/mm³ and/or the plasma HIV-1 RNA level rises above 30 000 copies/ml.

Once the decision to initiate therapy has been made, the options for potent regimens include: (1) a protease inhibitor (often pharmacologically enhanced by low-dose ritonavir) with 2 nucleoside analog RTIs; (2) a non-nucleoside RTI with 2 NRTIs; (3) 3 NRTIs (including abacavir); (4) 1–2 PIs plus an NNRTI with 1–2 NRTIs; (5) 2 PIs plus an NNRTI. The first 3 options are the most commonly used in clinical practice today. Considerations with respect to which regimen to choose include the desire to suppress viral load to levels below the detection limit of the most sensitive HIV-1 RNA assays available, tolerability, safety, predicted adherence, maintenance of future options and the potential for the primary acquisition of a drug resistant viral strain. Second-line therapy in the context of these options revolves around the following: a pre-planned switch following viral suppression to avoid toxicity or simplify a regimen; a switch for toxicity or intolerance; and intensification or a more complete switch for a suboptimal response or overt virologic failure. When selecting the specific components of the initial regimen, practical alternatives, depending upon the strategy chosen, should already be in hand and can be assisted by drug resistance testing in the circumstance of a suboptimal response or virologic failure. As new options from both existing and new drug classes emerge, the ability to choose simpler, less toxic, potent regimens and to have superior alternatives should translate into more complete and durable responses and ultimately a broader clinical benefit for HIV infected persons.

Presenting author: S Hammer

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2000-10-22
PL1-1

Originally published in AIDS Volume 14, 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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