This infectious molecular clone contained the HIV-1 AD8 env, mutations in Vpu that conferred improved activity against PTM tetherin, and CA mutations associated with intermediate PTM Mx2 resistance, and like the passaged viral swarm from which it was derived, stHIV-A19 consistently caused AIDS (marked by CD4+ T-cell depletion and the development of AIDS-defining clinical diseases) in CD8α+ cell-depleted PTMs. Here, CD4 is linked to AIDS.