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Suppression of viral rebound after 3BNC117 administration

HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption.

Scheid J.F., Horwitz J.A., Bar-On Y., Kreider E.F., Lu C.L., Lorenzi J.C., Feldmann A., Braunschweig M., Nogueira L., Oliveira T., Shimeliovich I., Patel R., Burke L., Cohen Y.Z., Hadrigan S., Settler A., Witmer-Pack M., West A.P. Jr, Juelg B., Keler T., Hawthorne T., Zingman B., Gulick R.M., Pfeifer N., Learn G.H., Seaman M.S., Bjorkman P.J., Klein F., Schlesinger S.J., Walker B.D., Hahn B.H., Nussenzweig M.C., Caskey M.

Interruption of combination antiretroviral therapy (ART) in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117, a broad and potent neutralizing antibody (bNAb) against the CD4 binding site of HIV-1 Env1, in the setting of analytical treatment interruption (ATI) in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Two or four 30 mg/kg infusions of 3BNC117, separated by 3 or 2 weeks, respectively, were generally well tolerated. The infusions were associated with a delay in viral rebound for 5-9 weeks after 2 infusions, and up to 19 weeks after 4 infusions, or an average of 6.7 and 9.9 weeks respectively, compared with 2.6 weeks for historical controls (p=<1e-5). Rebound viruses arose predominantly from a single provirus. In most individuals, emerging viruses showed increased resistance indicating escape. However, 30% of participants remained suppressed until antibody concentrations waned below 20 μg/ml, and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9-19 weeks. We conclude that administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during ATI in humans. Nature, 6/15/2016