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TREATMENT INTERRUPTION IN PATIENTS WITH MULTIPLE FAILURES TO ARV THERAPY: CAN THE CONTROVERSY BE SOLVED?
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Reported by Jules Levin
There has been an ongoing controversy over whether treatment interruption in very advanced patients improves response to salvage therapy compared to not having a treatment interruption. Several studies have found different results. A question surrounding this is whether reversion of resistance mutations to wild-type occurs during the interruption and if reversions are helpful in improving response. Here is a study presented at EACS (October 2003) attempting to answer the controversy.
In very advanced treatment-failing patients (VL 5.3 log10, 27 CD4/mm3), the GigHAART study has shown the benefit of an 8-week TI with a median reduction in VL of -1.91 log10 versus -0.37 log10 cp/ml at W12 in patients with TI versus no TI (P= 0.008) and a benefit of +54 versus +7 CD4/mm3 respectively at Week 24. By contrast, the Reverse study has evaluated in 23 patients (VL 5.14 log10, 43 CD4/mm3) a longer duration of TI (median 170 days) with multitherapy started after reversion of resistance mutations (RM) in > 2 classes and showed no benefit (+0.06 log10 cp/ml in VL, -27 CD4/mm3) at Week 24.
To explain this apparent discrepancy, we compared RM and number of sensitive ARV at baseline among those available and after TI among those prescribed.
In GigHAART, median baseline RM were 5, 2 and 7 for NRTI, NNRTI, PI; 5 patients (17%) had virus sensitive to <2 drugs; after TI, there was no change in the median RM, 23 patients (68%) had virus sensitive to > 2 drugs. In Reverse, the RM were 6, 2 and 9; 17 patients (74%) had no more than one sensitive drug; TI induced a change in median RM with 0 major for PI, 0 NNRTI and 2 TAMs; 16 patients (70%) had virus sensitive to > 2 drugs
This suggests that the key issue in the efficacy of a salvage therapy depends highly on the number of drugs remaining potentially active before any intervention.
Reference: 9TH EUROPEAN AIDS CONFERENCE (EACS), 1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP, October 25 - 29, 2003 Warsaw, Poland. Oral abstract: F7/5 - TREATMENT INTERRUPTION (TI) IN PATIENTS WITH MULTIPLE FAILURES TO ARV THERAPY: CAN THE CONTROVERSY BE SOLVED?. Costagliola D. (1), Duvivier C. (1,2), Delaugerre C. (3), Dominguez S. (1,2), Wirden M. (3), Ghosn J. (2), Calvez V. (3), Peytavin G. (4), Katlama C. (1,2). (1) INSERM E 0214, Universite Pierre et Marie Curie, (2) Département des Maladies Infectieuses et Tropicales, Hôpital Pitié-Salpétrière, (3) Laboratoire de Virologie, Hôpital Pitié-Salpétrière, (4) Département de pharmacologie, Hôpital Bichat-Claude Bernard, Paris, France
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