translation agency

AIDS Research and Therapy
The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?

<p>Frank Wiesmann<sup>1*,</sup> Jan Vachta<sup>1</sup>, Robert Ehret<sup>1</sup>, Hauke Walter<sup>2</sup>, Rolf Kaiser<sup>3,</sup> Martin St&uuml;rmer<sup>4</sup>, Andr&eacute; Tappe<sup>5</sup>, Martin D&auml;umer<sup>6</sup>, Thomas Berg<sup>7</sup>, Gudrun Naeth<sup>1</sup>, Patrick Braun<sup>1</sup> and Heribert Knechten<sup>1</sup></p>


February 13, 2011

Background

Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. Beside an enhancement of resistance, L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations.

Results

Based on a cohort of 47 L76V-positive patients, we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options.

Genotypic- and phenotypic HIV-resistance tests from 47 mostly multi-resistant, L76V-positive patients throughout Germany were accomplished retrospectively 1999-2009. Five genotype-based drug-susceptibility predictions received from online interpretation-tools for Atazanavir, Saquinavir, Amprenavir and Lopinavir, were compared to phenotype-based predictions that were determined by using a recombinant virus assay along with a Virtual Phenotype™(Virco). The clinical outcome of the L76V-adapted follow-up therapy was determined by monitoring viral load for 96 weeks.

Conclusions

In this analysis, the mostly used interpretation systems overestimated the L76V-mutation concerning Atazanavir- and SQV resistance. In fact, a clear benefit in drug susceptibility for these drugs was observed in phenotype analysis after establishment of L76V. More importantly, long-term therapy success was significantly higher in patients receiving Atazanavir and/or Saquinavir plus one L76V-selecting drug compared to patients without L76V-selecting agents (p = 0.002).

In case of L76V-occurrence ATV and/or SQV may represent encouraging options for patients in deep salvage situations.

*Corresponding author: Frank Wiesmann f.wiesmann@googlemail.com

CLICK HERE FOR PDF OF JOURNAL ARTICLE

© 2011 Wiesmann et al; licensee 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.





www.aegis.org