2. Academic Validation
  3. Cenicriviroc, a Novel CCR5 (R5) and CCR2 Antagonist, Shows In Vitro Activity against R5 Tropic HIV-2 Clinical Isolates

Cenicriviroc, a Novel CCR5 (R5) and CCR2 Antagonist, Shows In Vitro Activity against R5 Tropic HIV-2 Clinical Isolates

  • PLoS One. 2015 Aug 6;10(8):e0134904. doi: 10.1371/journal.pone.0134904.
Benoit Visseaux 1,  Charlotte Charpentier 1,  Gilles Collin 1,  Mélanie Bertine 1,  Gilles Peytavin 2,  Florence Damond 1,  Sophie Matheron 3,  Eric Lefebvre 4,  Françoise Brun-Vézinet 1,  Diane Descamps 1,  ANRS CO5 HIV-2 Cohort
Affiliations

Affiliations

  • 1 INSERM, IAME, UMR 1137, Paris, France; Univ Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Bichat, Laboratoire de Virologie, Paris, France.
  • 2 INSERM, IAME, UMR 1137, Paris, France; Univ Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Bichat, Pharmacologie des antirétroviraux, Paris, France.
  • 3 INSERM, IAME, UMR 1137, Paris, France; Univ Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Bichat, Service des Maladies Infectieuses et Tropicales, Paris, France.
  • 4 Tobira Therapeutics, Inc., South San Francisco, CA, United States of America.
PMID: 26247470 DOI: 10.1371/journal.pone.0134904
Abstract

Background: Maraviroc activity against HIV-2, a virus naturally resistant to different HIV-1 antiretroviral drugs, has been recently demonstrated. The aim of this study was to assess HIV-2 susceptibility to cenicriviroc, a novel, once-daily, dual CCR5 and CCR2 Antagonist that has completed Phase 2b development in HIV-1 Infection.

Methods: Cenicriviroc phenotypic activity has been tested using a PBMC phenotypic susceptibility assay against four R5-, one X4- and one dual-tropic HIV-2 clinical primary isolates. All isolates were obtained by co-cultivation of PHA-activated PBMC from distinct HIV-2-infected CCR5-antagonist-naïve patients included in the French HIV-2 cohort and were previously tested for maraviroc susceptibility using the same protocol. HIV-2 tropism was determined by phenotypic assay using Ghost(3) cell lines.

Results: Regarding the 4 R5 HIV-2 clinical isolates tested, effective concentration 50% EC50 for cenicriviroc were 0.03, 0.33, 0.45 and 0.98 nM, similar to those observed with maraviroc: 1.13, 0.58, 0.48 and 0.68 nM, respectively. Maximum percentages of inhibition (MPI) of cenicriviroc were 94, 94, 93 and 98%, similar to those observed with maraviroc (93, 90, 82, 100%, respectively). The dual- and X4-tropic HIV-2 strains were resistant to cenicriviroc with EC50 >1000 nM and MPI at 33% and 4%, respectively.

Conclusions: In this first study assessing HIV-2 susceptibility to cenicriviroc, we observed an in vitro activity against HIV-2 R5-tropic strains similar to that observed with maraviroc. Thus, cenicriviroc may offer a once-daily treatment opportunity in the limited therapeutic arsenal for HIV-2. Clinical studies are warranted.

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