Cross-reactive neutralizing humoral immunity does not protect from HIV type 1 disease progression

Broadly reactive neutralizing antibodies are the focus of human immunodeficiency virus (HIV) type 1 vaccine design. However, only little is known about their role in acquired immunodeficiency syndrome (AIDS) pathogenesis and the factors associated with their development. Here we used a multisubtype panel of 23 HIV-1 variants to determine the prevalence of cross-reactive neutralizing activity in serum samples obtained ∼35 months after seroconversion from 82 HIV-1 subtype B-infected participants from the Amsterdam Cohort Studies on HIV Infection and AIDS. Of these patients, 33%, 48%, and 20%, respectively, had strong, moderate, or absent cross-reactive neutralizing activity in serum. Viral RNA load at set point and AIDS-free survival were similar for the 3 patient groups. However, higher cross-reactive neutralizing activity was significantly associated with lower CD4⁺ T cell counts before and soon after infection. Our findings underscore the importance of vaccine-elicited immunity in protecting from infection. The association between CD4⁺ T cell counts and neutralizing humoral immunity may provide new clues as to how to achieve this goal.