Table 2.
Summary of raltegravir efficacy studies with antiretroviral-experienced patients
| Study | Design | Eligibility | Treatment | Efficacy results |
|---|---|---|---|---|
| Comparative trials | ||||
| BENCHMRK 1 and 27,9 | Phase III R, PC, MC 2:1 allocation ratio DB week 156 OL week 240 |
Age ≥16 years ART-experienced HIV-1 RNA >1,000 c/mL (on ART) 3 ART class resistance |
RAL 400 mg BID + OBT Placebo BID + OBT |
<400 c/mL in RAL arm (non-completion = failure) 16 weeks: 77%; 48 weeks: 72%; 96 weeks: 62%; 156 weeks: 54%; 240 weeks: 45% 77% of patients continuing from week 156 to week 240 maintained viral loads,50 c/mL with only 8 withdrawals due to virologic failure |
| Protocol 00539,40 | Phase II R, PC, MC 1:1:1:1 allocation ratio DB week 24 OL week 96 |
Age ≥18 years ART-experienced INSTI-naïve HIV-1 RNA >5,000 c/mL 3 ART class resistance |
RAL 200 mg BID + OBT RAL 400 mg BID + OBT RAL 600 mg BID + OBT Placebo BID + OBT |
<400 c/mL in RAL arm (non-completion = failure) 24 weeks: 70%; 48 weeks: 68%; 96 weeks: 55% Of the 94 RAL patients who entered the OL, only 3 discontinued prior to 96 weeks due to lack of efficacy |
| Study 14541 | Phase III R, DB, AC, MC 1:1 allocation ratio |
Age ≥18 years ART-experienced INSTI-naïve HIV-1 RNA >1,000 c/mL (on ART) 2 ART class resistance or 6 months’ experience with at least 2 classes of ART |
RAL 400 mg BID + EVG placebo Qday + boosted PI + 3rd agent EVG 150 mg Qday + RAL placebo BID + boosted PI + 3rd agent |
<50 c/mL in RAL arm (ITT) 48 weeks: 58%; 96 weeks: 45% Between weeks 48 and 96, virologic failure occurred in 6.3% of RAL patients |
| Non-comparative trials | ||||
| SALIR42 | OL, MC | ART-experienced | RAL 400 mg BID + OBT | 292/320 patients remained on their initial regimen at 96 weeks 273/300 patients still receiving RAL at week 96 achieved viral load <50 c/mL |
| TRIO43 | Phase II OL, MC |
HIV-1 RNA >1,000 c/mL (on ART) Naïve to RAL, DRV, ETR ≥3 PI resistance mutations, DRV susceptible ≥3 NRTI resistance mutations ETR susceptible |
RAL 400 mg BID + ETR 200 mg BID + DRV/r 600/100 mg BID ± OBT (T20 or NRTI) |
<50 c/mL (missing = failure) 24 weeks: 90%; 48 weeks: 86%; 96 weeks: 88% 19/103 patients with virologic failure in 96 weeks, 12 before 48 weeks, 7 between weeks 48 and 96 Virologic success did not differ regardless of presence of OBT |
Abbreviations: AC, active controlled; ART, antiretroviral therapy; BID, twice daily; c/mL, copies/milliliter; DB, double blind; DRV, darunavir; DRV/r, darunavir/ritonavir; ETR, etravirine; EVG, elvitegravir; INSTI, integrase strand-transfer inhibitor; ITT, intention-to-treat analysis; MC, multicenter; NRTI, nucleoside reverse-transcriptase inhibitor; OBT, optimized background therapy; OL, open label; PC, placebo controlled; PI, protease inhibitor; Qday, daily; R, randomized; RAL, raltegravir; RNA, ribonucleic acid; T20, enfuvirtide.