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  • Oral presentation
  • Open Access

Activity of the integrase inhibitor S/GSK1349572 in subjects with HIV exhibiting raltegravir resistance: week 24 results of the VIKING study (ING112961)

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Journal of the International AIDS Society201013 (Suppl 4) :O51

https://doi.org/10.1186/1758-2652-13-S4-O51

  • Published:

Keywords

  • Raltegravir
  • Integrase Inhibitor
  • Elvitegravir
  • Bone Marrow Aplasia
  • Optimise Background Regimen

Background

S/GSK1349572(572) showed potent activity in Phase 2 studies in INI-naive HIV-infected subjects and limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. VIKING is an ongoing 24-week Phase 2b pilot study assessing 572 in subjects with RAL-resistant HIV. A good antiviral response during the functional monotherapy phase (through Day 11) of this pilot study was observed with a strong correlation between baseline susceptibility to 572 and response.

Methods

27 RAL-experienced, adult subjects, with screening plasma HIV-1 RNA ≥1000c/mL and genotypic resistance to RAL and ≥ 2 other ART classes, received 572 50mg QD in Cohort I while continuing their failing regimen (without RAL). At Day 11 the background regimen was optimised, where feasible, and 572 continued. The antiviral activity (primary end-point at Day 11), tolerability, safety and virology data through Week 24 of Cohort I are presented. A higher dose is being assessed.

Results

At Baseline, subjects harboured viruses displaying high level resistance to RAL (median fold change in susceptibility [FC] 161, range: 0.57- >166) and low median FC to 572 (1.46, range: 0.55-35). Median (IQR) Baseline CD4+ and plasma HIV-1 RNA were 110 cells/mm3 (40, 230) and 4.47 log10c/mL (3.9, 4.9), respectively. Median number (range) of prior ART drugs was 18 (10, 23). Twenty one (78%) subjects achieved plasma HIV-1 RNA<400 c/mL (n=11) or ≥ 0.7 log10 c/mL decline (n=10) at Day 11 (primary end-point). Post Day 11, the optimised background regimen (OBR) phenotypic susceptibility score (PSS) was 0, 1 and ≥ 2 for 12 (44%), 7 (26%) and 8 (30%) subjects, respectively. 17 subjects continued therapy through Week 24 when 14/27 (52%) and 11/27 (41%) subjects achieved < 400 c/mL and < 50 c/mL, respectively by TLOVR. Response correlated with OBR PSS: 2/12 (17%) subjects with PSS =0, 4/7 (57%) with PSS=1 and 8/8 (100%) with PSS ≥2 achieved <400 c/mL at Week 24. Drug related AEs (any grade) were observed in 6 (22%) subjects. Two subjects with advanced AIDS died after withdrawal from study for SAEs (brain mass, non-Hodgkin's lymphoma with febrile bone marrow aplasia) unrelated to 572.

Conclusions

Despite high level baseline resistance to RAL and the limited activity of the OBR co-administered with 572, the majority of subjects achieved < 400 c/mL at Week 24 with improved response rates in those receiving at least one active background ART. S/GSK1349572 was generally well tolerated in this advanced population.

Authors’ Affiliations

(1)
UNC School of Medicine, Center for AIDS Research Clinical Care, NC, USA
(2)
Hopital Edouard Herriot, Lyon, France
(3)
Service de médecine interne et maladies infectieuses, Hôpital Saint André (CHU), Bordeaux, France
(4)
San Raffaele Scientific Institute, Milan, Italy
(5)
Hopital de la Pitie-Salpetriere, Paris, France
(6)
Southwest CARE Center, Santa Fe, USA
(7)
Shionogi & Co. Ltd., Osaka, Japan
(8)
GlaxoSmithKline, Uxbridge, UK
(9)
GlaxoSmithKline, Research Triangle Park, USA
(10)
GlaxoSmithKline, Mississauga, Canada

Copyright

© Min et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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