Given the apparent tolerance and anti-HIV effects of the C261Y substitution in human T cells, we considered this knock-in approach in the context of a “block-and-lock” functional cure scenario (81), employing a latency reporter system (60) to demonstrate that the CCNT1.C261Y cells remain susceptible to HIV-1 infection but are markedly refractory to drug-induced viral reactivation (Fig. 5). Here, CCNT1 is linked to HIV-1 infection.