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Once-daily S/GSK1349572 combination therapy in antiretroviral-naïve adults: rapid and potent 24-week antiviral responses in SPRING-1 (ING112276)

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  • 2,
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Journal of the International AIDS Society201013(Suppl 4):O50

https://doi.org/10.1186/1758-2652-13-S4-O50

Published: 8 November 2010

Keywords

  • Efavirenz
  • Virologic Failure
  • Antiviral Response
  • Integrase Inhibitor
  • Pharmacokinetic Variability

Purpose of study

S/GSK1349572, a next-generation HIV-1 integrase inhibitor, has previously demonstrated potent antiviral activity in Phase 2a with once-daily, unboosted dosing. SPRING-1 is an ongoing dose-ranging study designed to select a dose to for Phase 3 evaluation.

Methods

SPRING-1 is a Phase 2b, multicentre, partially-blinded study in therapy-naïve adults, randomized 1:1:1:1 to 10mg, 25mg or 50mg of S/GSK1349572 or efavirenz(EFV) 600mg once-daily with either co-formulated TDF/FTC or ABC/3TC.

Summary of results

205 subjects received study drug: 86% male, 20% non-white, 26%>100,000c/mL HIV-1 RNA, 67% TDF/FTC. Plasma HIV-1 RNA declined rapidly across all S/GSK1349572 doses with no differences in NRTI subgroups. Three protocol-defined virologic failures occurred, 1 on EFV (<1log10 decline by Week 4), and 2 on S/GSK1349572 (Week 4 and 24 rebound >400c/mL with no INI mutation detected). No dose-related clinical or laboratory toxicities were observed. More drug-related AEs of moderate-or-higher intensity were reported on EFV (20%) than S/GSK1349572 (6%) arms; none occurred in more than 1 S/GSK1349572 subject. The most frequent category of such events reported by subjects receiving EFV and S/GSK1349572 were gastrointestinal (4% vs. 2%, respectively); other frequent events on EFV were psychiatric (6%) and rash (4%) disorders. No SAE was considered related to S/GSK1349572. Six subjects (2: S/GSK1349572 and 4: EFV) withdrew due to AEs. Mean change from baseline in LDL cholesterol was +0.023mmol/L among S/GSK1349572 subjects and +0.468mmol/L among EFV subjects. S/GSK1349572 demonstrated low pharmacokinetic variability and drug exposure increased with dose. Table 1

Table 1

Planned Week 24 Interim Analysis Results

S/GSK1349572 10 mg (n=53)

S/GSK1349572 25mg (n=51)

S/GSK1349572 50mg (n=51)

EFV control (n=50)

Mean baseline HIV-1 RNA (log10 c/mL)

4.42

4.38

4.58

4.46

%<50c/mL at 24 wks (by TLOVR)

96% (51/53)

90% (46/51)

92% (47/51)

78% (39/50)

Median baseline (change from baseline at 24 weeks) CD4+ cells/mm3

289 (+159)

330 (+206)

305 (+167)

308 (+110)†

†p=0.008; Wilcoxon two-sample test vs. S/GSK1349572 arms (median change: +176)

Conclusions

S/GSK1349572 administered once-daily without a PK booster was well tolerated with potent antiviral activity at all doses explored in SPRING-1. The greater CD4+ cell increases on S/GSK1349572 merit further observation and confirmation.

Authors’ Affiliations

(1)
University of Bonn, Bonn-Venusberg, Germany
(2)
34th Street Community Health Center, Bakersfield, USA
(3)
Ospedali Riuniti de Bergamo, Bergamo, Italy
(4)
Hospital 12 de Octubre, Madrid, Spain
(5)
ICH Study Center, Hamburg, Germany
(6)
AIDS Center, Smolensk, Russian Federation
(7)
Hospital Bichat-Claude Bernard, Paris, France
(8)
GlaxoSmithKline, Toronto, Canada
(9)
GlaxoSmithKline, Research Triangle Park, USA

Copyright

© Rockstroh 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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