Background: New options for first-line treatment of HIV-2 infection are needed. We evaluated an integrase inhibitor (raltegravir)-containing regimen. Methods: ART-naive adults infected with HIV-2 only and history of CDC group B or C event, or a CD4 count <500 cells/muL, or a CD4 decrease >50 cells/muL/year over the past 3 years, or a confirmed plasma HIV-2 RNA (pVL) >/=100 copies (cp)/mL were eligible for this non-comparative trial. The composite primary endpoint was survival at 48 weeks (W48) without any of the following: CD4 gain from baseline <100 cells/muL, confirmed pVL >/=40 cp/mL from W24, raltegravir permanent discontinuation, incident B or C event. HIV-2 ultrasensitive pVL (uspVL) and total DNA were assessed using "in-house" PCR assays. Results: Baseline median CD4 count of 30 enrolled individuals (67% women) was 436 cells/microL (InterQuartile Range[IQR] 314- 507); pVL was >/=40 cp/mL in 20/30 (67%); uspVL was >/=5 cp/mL in 23/25 (92%); total DNA was >6 cp/PCR in 8/25 (32%). At W48, the composite endpoint of success was reached in 12/30 (40%; 95% Confidence Interval 22.7 to 59.4). Failure was mainly due to CD4 gain <100 cells/microL (n=15), UspVL was <5 cp/mL in 13/15 (87%) and total DNA >6 cp/PCR in 3/26 (12%). Median CD4 gain was +87 cells/microL (IQR +38- +213, n=28). No serious adverse reaction was reported. Conclusion: Raltegravir-containing cART is a safe option for first line treatment of HIV-2 infection, yielding a comparable success rate to protease inhibitors. UspVL and total DNA were undetectable in the vast majority of participants.< Réduire