Session 15Oral Abstract Presentations Treatment Strategies Session Day and Time: Wednesday 11:15 am - 12:45 pm Presentation Time: 12:15 Room: Auditorium
68 Long-term Benefit of Treatment Interruption in Salvage Therapy (GIGHAART ANRS 097) christine katlama*1, stephanie dominguez1, claudine duvivier1, constance delaugerre1, gilles peytavin2, mayeule legrand1, vincent calvez1, karine gourlain1, dominique costagliola3 1Hosp Pitié Salpêtrière, Paris, France; 2Hosp Bichat-Claude Bernard, Paris, France; and 3INSERM E 0214, 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.