Future Perspectives An interesting STR that is anticipated is the combination ABC/3TC/DTG. Dolutegravir is an unboosted integrase inhibitor that has been effectively and safely used for the

treatment of HIV-infected naïve (with 2 NRTIs) and experienced patients (with optimized background regimen) [57–59, 66, 67], (Table 2). DTG has shown to be effective with ABC/3TC or TDF/FTC regardless of blood level HIV-1 RNA [66], although the number of patients on ABC/3TC with high viral load is limited. The efficacy of DTG has been compared to raltegravir in the SPRING-2 (NCT#01227824) study; both associated with 2 NRTIs in cART-naïve patients: DTG 50 mg OD was as effective as raltegravir 400 mg BID at 96 weeks (81% vs. 76%). In the NRTI backbone comparison at 96 weeks those on DTG with ABC/3TC had efficacy rates of 74% compared to those on TDF/FTC of GSK126 mouse 86%. [57]. DTG has also

been compared to a boosted-PI, both associated with 2 NRTIs (TDF/FTC or ABC/3TC). The open-label FLAMINGO (NCT#01449929) BGJ398 supplier study has shown the superiority in efficacy of DTG compared to darunavir (DRV)/RTV at week 48, driven by higher discontinuations in the DRV arm. Virologic failure was observed in 2 patients (1%) on each arm without treatment-emergent resistance in either arm. The most common AEs were diarrhea with DRV/RTV and headache with DTG, while treatment-related study discontinuations were low (1% on DTG arm, 4% on DRV/RTV arm) [58]. In the SINGLE (NCT#01263015) study, enrolling Adenosine naïve patients, DTG 50 mg + ABC/3TC had a better safety profile and was more effective through 48 weeks than TDF/FTC/EFV. The time to reach HIV-RNA <50 copies/mL was 28 days with DTG vs. 84 days with EFV (p < 0.0001) and the increase in CD4

cells count was 267 with DTG vs. 208 with EFV (p < 0.001). The main AEs observed in the DTG arm were insomnia and a mild, non-progressive increase in the serum creatinine without any effect on the actual glomerular filtration rate. Discontinuation due to AEs was observed in 10% of the patients in the EFV arm vs. 2% in the DTG arm and the higher discontinuation rate in the EFV arm drove the overall greater efficacy. Moreover, in patients failing cART in the DTG arm, resistance to any of the regimen components did not develop [59]. The SINGLE study supported the idea of co-formulating ABC/3TC/DTG as a new promising STR whose limits might be related to the backbone: restricted use to patients HLAB*5701 negative. Dolutegravir is, since August 2013, approved in the US for the treatment of HIV-1 infection in combination with other ARV drugs, but studies exploring the potential of the ABC/3TC/DTG STR are ongoing, such as the ARV treatment in ART-naïve women (ARIA Study, NCT#01910402) [68].