Antibody therapy paired with antiretroviral therapy suppresses viral load long term in SIV+ macaques, even after treatment stops

HIV-infected individuals can manage their disease with antiretroviral therapy (ART). However, maintaining a drug regimen for life is difficult, and the search for a cure continues. Recently, Byrareddy et al. published an article in Science (October 2016; 354: 197–202) demonstrating that in simian immunodeficiency virus (SIV)+ macaques whose infection was controlled with ART, an antibody treatment resulted in undetectable viral loads even after researchers withdrew ART and the antibody therapy. The antibody that the researchers used targeted α4β7 integrin, a molecule expressed on CD4+ T cells, and is known to disrupt trafficking of HIV-infected cells to the gastrointestinal tissues where the virus replicates and forms reservoirs. Thus, it appears that by interfering with HIV's ability to hijack α4β7 integrin-expressing CD4+ T cells, this approach suppressed the virus long term in macaques, without the need for continuing therapy. Author Aftab Ansari (Professor, Emory University), who says these results took the team by surprise, explains that the most significant aspect of the study is that ‘the administration of an antibody that is almost identical to the one already approved by the US Food & Drug Administration for treating patients with Crohn's disease is able to control virus replication to undetectable levels for up to 2 years after all therapy has been stopped, when administered to SIV-infected rhesus macaques under the umbrella of short-term ART.’ Petronella Ancuta (Associate Professor, Université de Montréal), whose lab works on human HIV studies, notes, ‘The results are spectacular; they suggest that blocking α4β7-mediated migration in different tissues allows a functional cure. The data are very intriguing since it challenges our understanding of mechanisms of viral persistence during ART.’ With regard to the study's strengths, Ansari notes that in addition to controlling viral replication, this short-term, combined therapy also led to immune reconstitution to almost normal levels, both in the blood and in gastrointestinal tissues. In terms of limitations, he explains that the study required that therapy be initiated as early as 5 weeks postinfection, which might be difficult to achieve in HIV-infected humans. Ancuta also says that factors such as the genetic background of the animals or infection with less virulent SIV strains could have affected the results, and notes the need for replication by other labs. Anthony Fauci (Director, National Institute of Allergy and Infectious Diseases), also an author, says that plans to follow up on the results in humans are already underway: ‘We have begun the Phase 1 study in HIV-infected patients who have been virally suppressed on ART with the hope of successfully discontinuing ART after several doses of vedolizumab. It will take several months before even preliminary data are available.’ Ansari notes, ‘If this is translatable to human HIV-1 infected patients, it could lead to eliminating the requirement for a lifetime daily intake of ART.’ Acknowledgements Conflicts of interest There are no conflicts of interest.

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