Broadly neutralizing antibody responses in a Chinese acute HIV-1 infection cohort of men who have sex with men

Numerous broadly neutralizing antibodies (bnAbs) have been isolated from individuals with chronic HIV-1 infection, yet eliciting bnAbs through active immunization remains challenging. Investigating naturally infected patients whose plasma exhibits broadly neutralizing activity may reveal the factors driving bnAb development and inform vaccine design. We analyzed the clinical, immunological, and virological correlates of bnAb responses in a longitudinally followed, antiretroviral therapy (ART)-naïve, acute HIV-1 infection (AHI) cohort (n = 52) of men who have sex with men (MSM) in Shenyang, China. Neutralizing activity was assessed in participant plasma samples collected at the last available time point (LTP), prior to ART initiation, loss to follow-up, or the study data cutoff (median: 3.82 years, range: 3.14-4.82 years). To determine the occurrence and timing of HIV-1 multiple infection, we amplified and deep-sequenced the env C2-V4 and pol-RT regions (~450 bp) from plasma collected at baseline, one year, two years, and LTP. Individuals with multiple infection developed significantly stronger bnAb responses at LTP than those with monoinfection. Notably, acquisition of a second HIV-1 strain within or beyond one year after primary infection was associated with enhanced bnAb responses, with a higher odds ratio (OR) observed for superinfection occurring beyond one year. These findings indicate the potential role of immunogen diversity and immunization timing in bnAb induction, supporting vaccine strategies that mimic delayed sequential antigen delivery.