Combination therapy with broadly neutralizing antibodies, antiretroviral therapy and CCR5 blockade limits viral reservoir seeding in infant macaque model of HIV.

Lack of access to antiretroviral therapy (ART) leads to the transmission of human immunodeficiency virus in ~120,000 children annually, emphasizing the need for new strategies to prevent lifelong infection. Here in an infant rhesus macaque model of peripartum oral infection, we show that broadly neutralizing antibodies directed to the viral envelope protein were insufficient to prevent latent reservoir establishment, independent of daily ART. Blockade of the human immunodeficiency virus co-receptor CCR5 via the antibody leronlimab also failed to prevent reservoir establishment, but it significantly reduced reservoir seeding in lymphoid and gastrointestinal tissues. Following the treatment of infants with viraemia at 72 h post-infection with the combination of broadly neutralizing antibodies, ART and leronlimab, no subsequent evidence of replicating or latent virus and antiviral immunity was observed 1 year after treatment interruption. These findings suggest a synergy between broadly neutralizing antibodies, ART and CCR5 blockade for preventing viral reservoir establishment and offer potential improvements over current therapies for newborns exposed to human immunodeficiency virus.