CD4 and AIDS: Although molecularly engineered modifications to enable HIV-1 to circumvent macaque APOBEC3 restriction and perhaps engage the macaque CD4 receptor more effectively led to both increased acute viral replication levels and longer periods of detectable plasma viremia in PTMs, it was clear that additional adaptative changes would be required for mmHIV-1 to achieve sustained, elevated plasma viral loads and AIDS-like viral pathogenesis.