AEGiS-Glasgow [PL1.3] Salvage therapy

Seventh International Congress on Drug Therapy in HIV Infection

Glasgow, UK - 14-17 November 2004

[PL1.3] Salvage therapy

Int Cong Drug Therapy HIV 2004 Nov 14-18;7:Abstract No. PL1.3

Brian G. Gazzard
HIV/GUM, Chelsea and Westminister Hospital, London, UK

The term salvage therapy is an unfortunate one, raising images of wrecks on the sea shore but I shall assume that this term means resistance to all three of the presently available classes of drugs. The scale of this problem is presently unclear. Although marketing experience suggest that large numbers of patients have been exposed to all three classes of drugs, resistance to these agents is somewhat less common and with the correct application of modern antiretroviral therapy may become less common in the future. Most of our patients with triple class resistance have in fact been given sub-optimum therapy in the past (all that was available at the time), or were poorly adherent to a variety of previous drug regimes. Equally in a survey in our Unit, the causes of deaths of our patients are not primarily related to virological failure and lack of treatment options but more to the development of tumours and patients presenting late who died before antiretroviral therapy can become effective.

Various treatment options for these patients will be discussed. There was a vogue for structured treatment interruption and one study from France suggested that such an approach followed by multiple antiretroviral therapy may improve prognosis in terms of reductions in viral load. This study is counter-balanced by another study performed by the CPCRA in earlier disease in which the outcome was significantly worse in terms of clinical progression and CD4 count levels as a result of therapy. This latter study was at a much earlier stage of disease with higher CD4 counts than the French study and many patients had viable further options that would have made therapy successful without structured treatment interruption. The current view would be that structured treatment interruption in an attempt to cause the virus to revert to wild type is not likely to have a major impact on disease therapy. The French study also utilised large numbers of drugs in an attempt to find a combination that would work with a view that, drugs, even though there was resistance to them, might have some effect on reducing viral load. Such an approach is the subject of a randomised controlled trial (OPTIMA) and while cohort studies have shown some benefits from such an approach, this is at the expense of unexpected pharmacological interactions, a high pill burden and considerable toxicity. There is good evidence, both from randomised trials and cohorts that staying on some form of therapy is better than discontinuing. A more minimalist approach would therefore be that sufficient drugs should be retained to try and keep the CD4 count as high as possible (the most important predictor of imminent death).

The fusion inhibitor T20, which is now licensed, and Tipranavir which is shortly to be licensed have been mainly used in a salvage situation although the optimum positioning of both drugs remains to be determined. When either of these agents are used as the only active component of a combination, the viral load drops are often short lived although the CD4 count may rise for a more prolonged period. The belief of most clinicians and a post hoc analysis of the major studies performed with T20 (TORO 1 and 2) would suggest that these drugs would be better used in combination with other active agents and, therefore, the best method of treatment in salvage is to prevent it from occurring by using agents more judiciously at an earlier stage of disease. A number of other agents including new nucleosides, new NNRTIs, Capaverine and TMC125, and novel agents attacking either integrase or the process of interaction either between the CD4 receptor and GP120 or between CCR5 and GP 41 should also be licensed in the foreseeable future which gives further hope to people in this situation.

SESSION 1: TREATMENT STRATEGIES

2004-11-14
PL1.3

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