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Comparison of raltegravir vs efavirenz

Comparison of raltegravir vs efavirenz

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Comparison of raltegravir vs efavirenz

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  1. Comparison of raltegravir vs efavirenz • STARTMRK

  2. STARTMRK Study: raltegravir vs efavirenz,in combination with TDF/FTC • Design Randomisation* 1 : 1 Double-blind W48 W96 > 18 years ARV-naïve HIV RNA > 5,000 c/mL Any CD4 cell count No resistance to EFV, TDF or FTC N = 282 N = 284 *Randomisation was stratified by baseline HIV RNA (< or > 50,000 c/mL) and viral hepatitis co-infection status • Objective • Non inferiority of RAL vs EFV: % HIV RNA < 50 c/mL by per protocol, non-completer = failure analysis (lower margin of the 2-sided 95% CI for the difference = - 12%, 90% power) Lennox JL. Lancet 2009;374:796-806 STARTMRK

  3. STARTMRK Study: raltegravir vs efavirenz,in combination with TDF/FTC Baseline characteristics and patient disposition RAL was administered with or without food, EFV on an empty stomach at bedtime, TDF/FTC in the morning with food Lennox JL. Lancet 2009;374:796-806 STARTMRK

  4. RAL EFV STARTMRK Study: raltegravir vs efavirenz,in combination with TDF/FTC Response to treatment at week 48 HIV RNA < 50 c/mL HIV RNA < 50 c/mL at W48(observed-failure analysis) by baseline factors % Primaryanalysis Per protocol, observed-failure * 91.6 100 89.1 86.1 81.9 75 50 25 Mean CD4/mm3 increase at W48 (observed-failure analysis): 189 (RAL) vs 163 (EFV) (p = 0.0184) N = 281 282 263 258 PP, NC = F 95% CI for the difference = - 1.9; 10.3 95% CI for the difference = - 2.6; 7.7 * Exclusion of discontinuations due to intolerability or reasons unrelated to treatment Lennox JL. Lancet 2009;374:796-806 STARTMRK

  5. Safety at W48 STARTMRK Study: raltegravir vs efavirenz,in combination with TDF/FTC Lennox JL. Lancet 2009;374:796-806 STARTMRK

  6. Safety: neuropsychiatric symptoms At Week 8 CNS-related adverse events had occurred in 10% of RAL patients vs 18% of EFV patients (p = 0.0149) Retrospective sensitivity analysis (additional symptoms): > 1 CNS-related adverse event: 20% vs 52% (p < 0.0001) Most symptoms were self-limited At Week 48 Cumulative incidence of CNS-related adverse event was significantly lower in patients on RAL: 14% vs 23% in the main analysis (p = 0.0044); 26% vs 59% in the sensitivity analysis (p < 0.0001) These events were generally mild: 62% of RAL vs 79% of EFV Only 1 patient, on EFV, discontinued the trial because of CNS-related adverse event STARTMRK Study: raltegravir vs efavirenz,in combination with TDF/FTC Lennox JL. Lancet 2009;374:796-806 STARTMRK

  7. Virologic failure: definition Non-response = HIV RNA > 50 c/mL at W24 or time of premature study discontinuation without achievement of HIV RNA < 50 c/mL or Rebound = after an initial response, confirmed HIV RNA > 50 c/mL STARTMRK Study: raltegravir vs efavirenz,in combination with TDF/FTC * Genotyping was done only in patients with HIV RNA > 400 c/mL ** 4 additional patients genotyped when HIV RNA was > 400 c/mL but later achieved HIV RNA < 50 c/mL; 3 on RAL: resistance mutations to RAL evidenced in 1/1 (2 not amplified); 1 on EFV: no resistance mutation Lennox JL. Lancet 2009;374:796-806 STARTMRK

  8. Summary - Conclusion At 48 weeks of treatment, RAL was non-inferior to EFV, in combination with TDF/FTC RAL + TDF/FTC led to more rapid viral load decline (significantly more patients with HIV RNA < 50 c/mL for weeks 2 to 16) Greater increase in CD4 was observed in the RAL group Upon virologic failure, resistance mutations to RAL was found in half of the cases (for which genotyping was performed) RAL was associated with significantly fewer overall and drug-related clinical adverse events, and CNS-related adverse events than was EFV Mean changes in lipid parameters were smaller for RAL than for EFV RAL + TDF/FTC is an alternative to EFV + TDF/FTC for first-line combination regimen in treatment-naïve HIV-infected patients STARTMRK Study: raltegravir vs efavirenz,in combination with TDF/FTC Lennox JL. Lancet 2009;374:796-806 STARTMRK