A die is cast: autologous neutralizing antibody resistance shapes the HIV reservoir during uninterrupted ART.

Initial efforts to control HIV infection include an autologous neutralizing antibody (aNAb) response. aNAbs bind Env trimers of the infecting HIV strain to neutralize virus but are not very effective at controlling HIV, as the virus quickly develops escape mutations to evade neutralization. Nevertheless, recent evidence suggests that aNAbs exert ongoing immune pressure on viral isolates in people living with HIV (PWH) treated with anti-retroviral therapy (ART) during chronic and early infection. In this issue of the JCI, McMyn et al. studied the dynamics of aNAb resistance in a cohort of 31 PWH treated with ART. Notably, a large proportion of HIV reservoir viral isolates were resistant to aNAb neutralization, which correlated with longer duration on uninterrupted ART, suggesting that selection for aNAb-resistant isolates occurs as reservoir cells containing neutralization-sensitive isolates are eliminated. aNAb resistance was not attributed to waning antibody response, which persisted for over 20 years despite viral suppression.