HTB

Lack of impact on viral reservoir with α4β7 monoclonal antibody vedolizumab: macaque results not matched in humans

Simon Collins, HIV i-Base

In 2016, impressive results generated headline news in Science after vedolizumab in a monkey study generated SIV remission without ART in approximately half the animals. [1]

Unfortunately, an extension to this study trying to duplicate the first results (using12 active and 10 controls) was presented at AIDS 2018, but found no differences in the active vs control groups. [2]

Also unfortunately, the first results using vedolizumab (already FDA-approved as a treatment for Crohn’s  disease) in a human study also failed to see any effect.

Although two studies included results that suggest vedolizumab might be safe in HIV positive people [3, 4], there was no impact on time to viral rebound after stopping ART in 18 participants, even after various post hoc analysis (using historical controls to overcome the lack of a control arm in the open-label study). There was considerable variability in the range of results however that did include two cases without viral rebound. [4]

Nevertheless, presenting these results, NIAID director Anthony Fauci “remained optimistic” about passive transfer of combinations of monoclonal antibodies during acute HIV infection.

References

  1. Byrareddy SN et al. Sustained virologic control in SIV+ macaques after antiretroviral and a4b7 antibody therapy. Science (2016), 354(6309):197-202. (14 Oct 2016). DOI: 10.1126/science.aag1276.
    http://science.sciencemag.org/content/354/6309/197
  2. Di Mascio M et al. Evaluation of an antibody to Alpha4Beta7 in the control of SIV infection. AIDS 2018, 23-27 July 2018, Amsterdam. Oral abstractTUAA0206LB.
    http://programme.aids2018.org/Abstract/Abstract/13267
  3. Thornhill JP et al. Two case reports on safety and impact of α4β7 integrin monoclonal antibody in treated primary HIV infection on HIV reservoirs. AIDS 2018, 23­–27 July 2018, Amsterdam. PosterTHPEB098.
    http://programme.aids2018.org/Abstract/Abstract/8033
  4. Fauci A et al. Durable control of HIV infections in the absence of antiretroviral therapy
    http://programme.aids2018.org/Programme/Session/37 (slides)
    https://www.youtube.com/watch?v=KK05hDfLKKE (webcast)

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