Disease progression due to dual infection in an HLA-B57-positive asymptomatic long-term nonprogressor infected with a nef-defective HIV-1 strain

We describe the case of an HLA-B57-positive long-term nonprogressor in whom we previously showed that PBMCs accumulated HIV-1 subtype B proviruses defective in the env gene. After more than 10 years of control of infection, plasma viremia increased progressively, with a concomitant loss of CD4+ T cells. By phylogenetic analyses of env, nef, vif, and gag sequences obtained at different time points, we suggest here that this patient was initially infected by a putatively attenuated nef-defective variant and that loss of control was due to superinfection with a fully competent virus belonging to the same clade B. At the time of superinfection, its plasma was unable to efficiently neutralize the superinfecting virus and moderate Gag-specific CD8+ T-cell responses were observed. This suggests the limited capacity of even a long-lasting natural infection with a nef-deficient HIV-1 strain to elicit immune responses able to prevent and control superinfection with a virus of the same clade.