At the recent XVIII International AIDS Conference in Vienna, investigators presented interim results of SPRING-1, a Phase 2b partially blinded dose-ranging study of the integrase inhibitor S/GSK 572. Approximately 200 treatment-naive subjects were randomized to 1 of 3 dosages of S/GSK 572 (10, 25, or 50 mg) or to efavirenz, coadministered with 2 NRTIs selected by investigators. NRTI combinations were either tenofovir/emtricitabine (67%) or abacavir/lamivudine (33%). All components were given once daily. The mean baseline HIV RNA level was 4.46 log10 copies/mL and the mean baseline CD4 count was 324 cells/µL.
In planned interim analysis at week 16, 90-96% of subjects in the S/GSK 572 groups had HIV RNA levels of <50 copies/mL, compared with 60% of the efavirenz group. CD4 count increases were 165 cells/µL in the overall S/GSK 572 group and 116 cells/µL in the efavirenz group. Adverse effects and lipid elevations were less common in the S/GSK 572 groups than in the efavirenz group; rash and neuropsychiatric symptoms were not seen in S/GSK 572 recipients.
Clinical Bottom Line
The rapid decline in HIV RNA levels seen in the S/GSK 572 groups (also seen in studies of the currently available integrase inhibitor, raltegravir) is impressive but is of unclear clinical significance. Longer-term and more robust data from this trial and others are required, but if these early efficacy and safety data hold up on further study, S/GSK 572 may offer another good once-daily option for initial treatment (with the potential for coformulation with NRTIs into a single fixed-dose combination pill for daily therapy). The dosage selected for Phase 3 studies is 50 mg daily.
- Arribas J, Lazzarin A, Raffi F, et al. Once-daily S/GSK1349572 as part of combination therapy in antiretroviral-naive adults: rapid and potent antiviral responses in the interim 16-week analysis from SPRING-1 (ING112276). In: Program and abstracts of the XVIII International AIDS Conference; July 18-23, 2010; Vienna. Abstract THLBB205.