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  • Oral presentation
  • Open Access

O214. Virological findings from the SARA trial: boosted PI monotherapy as maintenance second-line ART in Africa

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Journal of the International AIDS Society201013 (Suppl 4) :O20

https://doi.org/10.1186/1758-2652-13-S4-O20

  • Published:

Keywords

  • Viral Load
  • Darunavir
  • Virological Suppression
  • Virological Finding
  • Boost Protease Inhibitor

Background

The SARA trial recently demonstrated a non-inferior CD4 response, over median follow-up of 60 weeks, with a boosted protease inhibitor monotherapy (bPImono) maintenance second-line regimen compared with continuous combination therapy (CT), suggesting this approach could maintain effectiveness whilst improving tolerability and decreasing costs [International AIDS Conference 2010, LBPE16]. Analysis of virological response and genotypic drug resistance is reported here.

Methods

Eligible participants in the DART trial who received 24 weeks of lopinavir/ritonavir-containing second-line CT were randomised to maintain current CT or to reduce to bPImono within a nested pilot trial (SARA). No real-time virology was performed, but stored plasma samples from time at switch to second-line, randomisation after 24 weeks of second-line, and 24 weeks after randomisation were assayed for HIV-1 RNA viral load (VL) by Roche Amplicor v1.5. Genotypic resistance was assessed on samples with VL >1000 c/ml at this latest time point, along with paired samples at switch to second-line. All analyses are intention-to-treat.

Results

192 participants were randomised to CT (n=95) or bPImono (n=97). 77% (135/173) had VL<50 c/ml at randomisation. 44 (23%) participants were taking bPI with NRTI only, 29 (15%) with NNRTI only, and 119 (62%) with both. Virological suppression at week 24 was higher (trend test p=0.007) for participants on CT vs bPImono: 77% (70/91) vs 60% (56/94) had VL <50 c/ml, 90% (82) vs 74% (72) had VL <200 c/ml, and 94% (86) vs 84% (81) had VL <1000 c/ml. Restricting to patients with VL <50 c/ml at randomisation, 85% (57/67) vs 66% (43/65) had VL <50 c/ml at week 24. Of the 18 participants with VL >1000 c/ml at week 24, 12 (2 CT, 10 bPImono) have been assessed genotypically. IAS major PI mutations at week 24, not present at switch to second-line, were detected in 2 bPImono participants only. One participant (VL=3600 c/ml) had I54V only, the other (VL=1490 c/ml) M46IM+V82AV. Both isolates were considered fully susceptible to darunavir.

Conclusions

In this study based on retrospective virological testing, bPImono following 24 week second-line induction was associated with an increase in low level viraemia, although generally in the absence of PI resistance. Longer-term trials are required before definitive conclusions can be drawn about the effectiveness of PI monotherapy in populations without access to virological monitoring.

Authors’ Affiliations

(1)
University College London, London, UK
(2)
MRC Clinical Trials Unit, London, UK
(3)
Imperial College, London, UK
(4)
Ninewells Hospital and Medical School, Dundee, UK
(5)
MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda
(6)
Joint Clinical Research Centre, Kampala, Uganda
(7)
University of Zimbabwe, Harare, Zimbabwe
(8)
Virology Group, and Trial Team, Uganda

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