Infection with HIV-1 with tropism for lymphocytes expressing the CXCR4 co-receptor (X4 HIV, or CXCR4-tropic HIV) [1,2] has been consistently associated with lower CD4+T-cell counts in antiretroviral treatment (ART)-naïve and -experienced subjects [3,4], and with faster disease progression in untreated patients [5–7], independently of their baseline CD4+T-cell counts or HIV-1 RNA levels [8,9]. This evidence concerns the gene CD4 and infection.