Neutralizing antibodies associated with viremia control in a subset of individuals after treatment of acute human immunodeficiency virus type 1 infection

Immediate treatment of acute human immunodeficiency virus type 1 (HIV-1) in fection has been associated with subsequent control of viremia in a subset of patients after therapy cessation, but the immune responses contributing to control have not been fully defined. Here we examined neutralizing antib odies as a correlate of viremia control following treatment interruption in HIV-1-infected individuals in whom highly active antiretriviral therapy (H AART) was initiated during early seroconversion and who remained on therapy for 1 to 3 years. Immediately following treatment interruption, neutralizi ng antibodies were undetectable with T-cell-line adapted, strains and the a utologous primary HIV-1 isolate in seven of nine subjects. Env- and Gag-spe cific antibodies as measured by enzyme-linked immunosorbent assay were also low or undetectable at this time. Despite this apparent poor maturation of the virus-specific B-cell response during HAART, autologous neutralizing a ntibodies emerged rapidly and correlated with a spontaneous downregulation in rebound viremia following treatment interruption in three subjects. Cont rol of rebound viremia was seen in other subjects in the absence of detecta ble neutralizing antibodies. The results indicate that virus-specific B-cel l priming occurs despite the early institution of HAART, allowing rapid sec ondary neutralizing-antibody production following treatment interruption in a subset of individuals. Since early HAART limits viral diversification, w e hypothesize that potent neutralizing-antibody responses to autologous vir us are able to mature and that in some persons these responses contribute t o the control of plasma viremia after treatment cessation.