Table 2.
Summary of major clinical studies of raltegravir
| Study | Phase | No. of participants | Study regimen | VL < 50 | CD4 countΔ | Comment/ref # |
|---|---|---|---|---|---|---|
| Protocol 004 | ||||||
| Part 1 | II | 35 treatment-naïve, HIV-1-infected patients | RAL (100, 200, 400, 600 mg), or placebo twice daily for 10 days | N/A | N/A | VL ↓1.9log10 (RAL 100 mg) 2.0log10 (RAL 200 mg) 1.7log10 (RAL 400 mg) 2.2log10 (RAL 600 mg)27 |
| Part 2 | II | 198 treatment-naïve, HIV-1-infected patients | TDF + 3TC and RAL 100, 200, 400, or 600 mg twice daily or EFV for 48 weeks | 85% (RAL 100 mg) 83% (RAL 200 mg) 88% (RAL 400 mg) 88% (RAL 600 mg) 87% (EFV) |
↑221 (100 mg) ↑146 (200 mg) ↑144 (400 mg) ↑187 (600 mg) ↑170 (EFV) |
28 |
| Extension | II | 198 treatment-naïve, HIV-1-infected patients | TDF + 3TC and RAL 400 mg twice daily or EFV for 96 weeks | 83% (RAL) 84% (EFV) |
↑221 (RAL) ↑232 (EFV) |
29 |
| STARTMRK | ||||||
| 48 weeks | III | 563-treatment-naïve, HIV-1-infected patients | TDF + FTC and RAL 400 mg twice daily of EFV | 86% (RAL) 82% (EFV) |
↑189 (RAL) ↑163 (EFV) |
30 |
| 96 weeks | III | 477 treatment-naïve, HIV-1-infected patients | Same as above | 81% (RAL) 79% (EFV) |
↑240 (RAL) ↑225 (EFV) |
31 |
| Protocol 005 | ||||||
| 24 weeks | II | 178 treatment-experienced, HIV-1-infected patients | OBT plus RAL (200, 400, or 600 mg) twice daily or placebo | 65% (RAL 200 mg) 56% (RAL 400 mg) 67% (RAL 600 mg) 13% (placebo) |
↑63 (200 mg) ↑113 (400 mg) ↑94 (600 mg) ↑5.4 (placebo) |
32 |
| 96 weeks | same as above | OBT plus RAL 400 mg twice daily or placebo | 55% (RAL) | ↑104 (RAL) | 33 | |
| BENCHMRK | ||||||
| 48 weeks Trial 1 |
III | 350 treatment-experienced HIV-1-infected patients | OBT and RAL 400 mg twice daily or placebo | 65% (RAL) 31% (placebo) |
↑109 (RAL) ↑45 (placebo) (Trial 1 and 2) |
34 |
| Trial 2 | 349 treatmentexperienced HIV-1-infected patients | Same as above | 60% (RAL) 35% (placebo) |
See above | ||
| 96 weeks (Trial 1 and 2) | III | 699 treatment-experienced HIV-1-infected patients | Same as above | 57% (RAL) 26% (placebo) |
↑123 (RAL) ↑49 (placebo) |
35 |
| SWTCHMRK | III | 702 HIV-1-infected patients with viral suppression on LPV/r-based regimen | OBT + LPV/r or switch to OBT + RAL for 24 weeks | 84% (RAL) 91% (control) |
↑5–17 (both groups) | 58 |
| SPIRAL | III | 273 HIV-1-infected patients with viral suppression on PI-based regimen | OBT + PI/r or switch to RAL for 48 weeks | 89% (RAL) 87% (control) |
↑46 (RAL) ↑44 (placebo) |
59 |
| SHIELD | II | 35 treatment-naïve HIV-1-infected patients | Single arm of ABC/3TC + RAL for 48 weeks | 91% | ↑247 | First study looking at RAL with alternative NRTI background62 |
| SPARTAN | II | 93 treatment-naïve HIV-1 infected-patients | ATV/RAL or ATV/r + TDF/FTC for 24 wks | 75% (ATV/RAL) 63% (ATV/r + TDF FTC) |
Not reported | Terminated early due to resistance in ATV/RAL group, hyperbilirubinemia22 |
Abbreviations: ATV, atazanavir; ABC, abacavir; 3TC, lamivudine; EFV, efavirenz; FTC, emtricitabine; LPV/r, lopinavir/ritonavir; OBT, optimized background therapy; PI, protease inhibitor; RAL, raltegravir; TDF, tenofovir; VL, viral load.