HIV 1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption
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 Env, 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 mg/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