[WePeB5887] Benefits of Treatment Interruption (TI) in Patients with Multiple Therapy Failures, CD4 cells <200 /mm³ and HIV RNA >50 000 cp/ml (GIGHAART ANRS 097)

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Benefits of Treatment Interruption (TI) in Patients with Multiple Therapy Failures, CD4 cells <200 /mm³ and HIV RNA >50 000 cp/ml (GIGHAART ANRS 097)

[AUTHOR(S):] C Katlama, S Dominguez, C Duvivier, C Delaugerre, M Legrand, V Calvez¹, G Peytavin², D Costagliola, GIGHAART Study³

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. WePeB5887

BACKGROUND: Megahaart was shown to rescue severe clinical situations and TI to favour the return of wild type virus. To evaluate the impact of TI on the efficacy of a subsequent multidrug therapy in patients (pts) with a history of failure to at least 2 NRTI, 1NNRTI and 2 PI and severe biological failure an open, prospective, multicentre, randomised study was conducted.

METHODS: Pts were randomised to either Immediate GIGHAART therapy (Imm.G) or Deferred GIGHAART (Def.G) after 8 weeks of TI. Gighaart regimen consisted in 3-4 NRTI + 1NNRTI ± Hydroxyurea (500mg bid) + ritonavir (400 mg bid) + amprenavir (600 mg bid) or lopinavir + a third PI (indinavir 400mg bid or saquinavir 600mg bid or nelfinavir 1250mg bid). The primary end-point was a decrease in plasma HIV-1 RNA >1 log₁₀ after 12 weeks of therapy (W 12/20). Due to the interim analysis, the final significance level is 0.0418

RESULTS: 70 patients were randomised, 68 pts started study drugs and 63 were evaluated at W12/20. At baseline, median plasma HIV RNA was 5.3 log₁₀ cp/ml, CD4 27/mm³, duration of ARV therapy was 6.6 years, with previous exposure to 11 ARV. During TI, the median HIV RNA increase was + 0.16 log₁₀ cp/ml and the median CD4 count decrease -10/mm³. By ITT missing equal failure analysis, an HIV RNA decrease >1log₁₀ from BL to W12/20 was observed in 26% vs 62% (p= 0.007), with 15% vs 38% of pts having HIV RNA < 400 copies/ml (p= 0.053) respectively in Imm. G vs Def. G. The observed median decrease in HIV RNA was - 0.37log₁₀ vs -1.91 log₁₀ (p=0.008) respectively in Imm. G and Def. G groups. Tolerance was acceptable. Gigatherapy reduction (<6 drugs) occurred in 5 pts. Follow-up until 24 weeks is on going.

CONCLUSIONS: In patients with extensive viral resistance and no current therapeutic options, a TI of 8 weeks followed by a multi-drug salvage regimen induces, after 12 weeks, a significantly higher benefit than no TI in terms of antiviral efficacy.

Presenting author: C. Katlama

1. Hopital Pitie-Salpetriere, Paris, France

2. Hopital Bichat, Paris, France

3. INSERM SC4, Paris, France

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