Katlama C, Dominguez S, Duvivier C, Delaugerre C, Peytavin G, Legrand M, Calvez V, Gourlain K, Costagliola D; Conference on Retroviruses and Opportunistic Infections.
Abstr 10th Conf Retrovir Oppor Infect Feb 10 14 2003 Hynes Conv Cent Boston Mass USA Conf Retrovir Oppor Infect 10th 2003 Boston Mass. 2003 Feb 10-14; 10: abstract no. 68.
Hosp Pitie Salpetriere, Paris, France
BACKGROUND: Megahaart was shown to rescue severe clinical situations and TI to favor the return of wild-type virus. Objective: To evaluate the benefit of TI in patients (pts) with multiple failure of therapy in a context of very advanced HIV disease (HIV VL > 50,000cps/ml and CD4cells < 200/mm3).METHODS: Open, prospective, multicentre, randomized study Pts were randomized to either Immediate GIGHAART therapy (Imm.G) or Deferred GIGHAART (Def.G) after 8 wks of TI. Gighaart regimen consisted in 3-4 NRTI + 1NNRTI +/- Hydroxyurea (500 mg bid) + ritonavir (400 mg bid) + amprenavir (600 mg bid) or lopinavir + a third PI (indinavir 400 mg bid or saquinavir 600 mg bid or nelfinavir 1,250 mg bid). The primary end-point was a decrease in plasma HIV-1 RNA > 1 log10 after 12 wks of therapy (W 12/20), but 64 pts were followed up to wk 48.RESULTS: Seventy (70) pts were randomized, 68 started study drugs, and 63 were evaluated at W12, W24, and 64 at W48. At baseline, median plasma HIV RNA was 5.3 log10 cp/ml, CD4 27/mm3, duration of ARV therapy was 6.6 yrs with a median of 11 antiretroviral drugs. By ITT missing equal failure analysis, the percentage of pts with HIV VL decrease > 1 log10 from baseline was in the Imm.G 26% at W12, 24% at W24, versus 62% at W12 and 50% at W24 in the Def.G (p = 0.007 and p = 0.043, respectively) Median decrease in HIV RNA from baseline was -0.37 at W12, -0.29 at W24, and -0.37 at W48 in the Imm.G versus -1.91 at W12, -1.08 at W24, and -0.79 at W48 (p = 0.008 at W12, p = 0.013 at W24) Percentage of pts with HIV RNA < 400 cp/ml was 15% at W12, 12% at W24 in the Imm.G vs 38% at W12, and 32% at W24 in the Def.G ( p = 0.053 and p = 0.077, respectively) Median increase in CD4 cell count from baseline was +7/mm3 at W24 and W48 in the Imm.G vs +51/mm3 at W24 and +69/mm3 at W48 in the Def.G. Tolerance was acceptable, 22% in the Imm.G and 47% in the Def.G were still on a gighaart regimen (treatment with more than 6 drugs) at wk 48. Three (3) major factors were associated with virologic success: treatment interruption with reversion of resistance, (RH = 12.4), adequate drug concentration (RH = 5.6), and the use of lopinavir (RH = 6.0).CONCLUSIONS: Treatment interruption followed by a multidrug salvage therapy induces a significant virologic and immunological benefit up to 48 wks.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Antiretroviral Therapy, Highly Active
- CD4 Lymphocyte Count
- Drug Therapy, Combination
- HIV Infections
- HIV Seropositivity
- HIV-1
- Humans
- Indinavir
- Longitudinal Studies
- Pyrimidinones
- Ritonavir
- Salvage Therapy
- Saquinavir
- Sulfonamides
- W 12
- amprenavir
- drug therapy
- lopinavir
- therapy
Other ID:
UI: 102261313
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