Antiviral activity of dolutegravir in subjects with failure on an integrase inhibitor-based regimen: week 24 phase 3 results from VIKING-3

Background : VIKING-3 aimed to examine efficacy and safety of dolutegravir (DTG) 50 mg twice daily in patients with resistance to multiple ARV classes, including integrase inhibitors (INI). Methods : RAL and/or EVG-resistant (current or historical) adult subjects with screening plasma HIV-1 RNA ≥500 c/mL and resistance to ≥2 other ART classes received open-label DTG 50 mg BID while continuing their failing regimen (without RAL/EVG). At Day 8 the background regimen was optimised and DTG continued. Activity of the optimized background regimen (OBR) was determined by Monogram Net Assessment. Primary endpoints were antiviral efficacy at Day 8 and Week 24. Results : 183 subjects enrolled, 124 with INI-resistance at screening and 59 with historical (but no screening) resistance. Population was advanced: at BL, median CD4 140, prior ART 13 yrs, 56% CDC Class C; 79% had >2 NRTI, 75% >1 NNRTI, and 70% >2 PI resistance-associated mutations, and 61% had non-R5 HIV detected. Of the 114 subjects who had the opportunity to complete 24 weeks on study before data cutoff, 72 (63%) had 2, respectively. Discontinuations due to adverse events were uncommon (6/183, 3%); the most common drug-related AEs were diarrhoea, nausea and headache, each reported in only 5% of subjects. Conclusion : A majority of the highly treatment-experienced subjects in VIKING-3 achieved suppression with DTG-based therapy. Responses were associated with Baseline IN genotype but not OSS, highlighting the importance and independence of DTG antiviral activity. DTG had a low rate of discontinuation due to adverse events at 50 mg BID in this advanced patient population. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Nichols G et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18112 http://www.jiasociety.org/index.php/jias/article/view/18112 | http://dx.doi.org/10.7448/IAS.15.6.18112