Adeno-Associated Virus Delivery of Anti-HIV Monoclonal Antibodies Can Drive Long-Term Virologic Suppression

Long-term delivery of anti-HIV monoclonal antibodies (mAbs) using adeno-associated virus (AAV) vectors holds promise for the prevention and treatment of HIV infection. We describe a therapy trial in which four rhesus monkeys were infected with SHIV-AD8 for 86 weeks before receiving the AAV-encoded mAbs 3BNC117, 10-1074, and 10E8. Although anti-drug antibody (ADA) responses restricted mAb delivery, one monkey successfully maintained 50–150 μg/mL of 3BNC117 and 10-1074 for over 2 years. Delivery of these two mAbs to this monkey resulted in an abrupt decline in plasma viremia, which remained undetectable for 38 successive measurements over 3 years. We generated two more examples of virologic suppression using AAV delivery of a cocktail of four mAbs in a 12-monkey study. Our results provide proof of concept for AAV-delivered mAbs to produce a “functional cure.” However, they also serve as a warning that ADAs may be a problem for practical application of this approach in humans. [Display omitted] •Chronically SHIV-infected macaques were treated with AAV-delivered bnAbs•Long-term virologic suppression is possible with AAV-delivered antibodies•A functional cure was achieved in one SHIV-infected macaque•Development of host-generated anti-antibodies limited treatment effectiveness Although anti-retroviral drug therapy can suppress HIV viral replication, it is not a cure. Martinez-Navio et al. report the functional cure of the “Miami monkey,” in which long-term SHIV suppression was achieved after a single administration of adeno-associated viruses (AAVs) encoding broadly neutralizing antibodies. They also report that host-generated anti-antibodies can hamper the applicability of this approach.