Highly potent and broadly neutralizing anti-HIV 1 antibodies (bNAbs) have been used to prevent and treat lentivirus infections in humanized mice, macaques and humans. To determine whether the administration of a combination of bNAbs during the acute SHIV infection of rhesus macaques might lead to long-term control of virus replication, animals challenged with SHIVAD8-EO by mucosal or intravenous routes, received a single 2-week course of 2 potent passively transferred bNAbs (3BNC117 and 10-1074). Viremia remained undetectable for 56-177 days, depending on bNAb half-life in vivo. Moreover, in the 13 treated monkeys, plasma virus loads subsequently declined to undetectable levels in 6 controller macaques. 4 additional animals maintained normal CD4+ T cell counts and low levels (300 to 600 Viral RA copies/ml plasma) of persistent viremia for over 2 years. The frequency of cells carrying replication-competent virus was undetectable or less than 1 per 106 circulating CD4+ T cells in the 6 elite controller macaques. Infusion of a T cell depleting anti-CD8 mAb to the elite controller animals led to a specific decline in levels of CD8+ T cells and rapid reappearance of plasma viremia. In contrast, macaques treated for 2 or for 15 weeks with combination anti-retroviral therapy (cART), beginning on day 3 after infection, experienced rebound plasma viremia shortly after treatment was interrupted. We conclude that passive immunotherapy during the acute SHIV infection differs from cART in that it facilitates the emergence of potent CD8+ T cell immunity able to durably suppress virus replication.
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