ACTIVATION OF VIRUS-REPLICATION AFTER VACCINATION OF HIV-1-INFECTED INDIVIDUALS

Little is known about the factors that govern the level of HIV-1 repli cation in infected individuals. Recent studies (using potent antiviral drugs) of the kinetics of HIV-1 replication in vivo have demonstrated that steady-state levels of viremia are sustained by continuous round s of de novo infection and the associated rapid turnover of CD4(+) T l ymphocytes. However, no information is available concerning the biolog ic variables that determine the size of the pool of T cells that are s usceptible to virus infection or the amount of virus produced from inf ected cells. Furthermore, it is not known whether all CD4(+) T lymphoc ytes are equally susceptible to HIV-1 infection at a given time or whe ther the infection is focused on cells of a particular state of activa tion or antigenic specificity. Although HIV-1 replication in culture i s known to be greatly facilitated by T cell activation, the ability of specific antigenic stimulation to augment HIV-1 replication in vivo h as not been studied. We sought to determine whether vaccination of HIV -1-infected adults leads to activation of virus replication and the ta rgeting of vaccine antigen-responsive T cells for virus infection and destruction. Should T cell activation resulting from exposure to envir onmental antigens prove to be an important determinant of the steady-s tate levels of HIV-1 replication in vivo and lead to the preferential loss of specific populations of CD4(+) T lymphocytes, it would have si gnificant implications for our understanding of and therapeutic strate gies for HIV-1 disease. To begin to address these issues, HIV-1-infect ed individuals and uninfected controls were studied by measurement of immune responses to influenza antigens and quantitation of virion-asso ciated plasma HIV-1 RNA levels at baseline and at intervals after immu nization with the trivalent influenza vaccine. Influenza vaccination r esulted in readily demonstrable but transient increases in plasma HIV- 1 RNA levels, indicative of activation of viral replication, in HIV-1- infected individuals with preserved ability to immunologically respond to vaccine antigens. Activation of HIV-1 replication by vaccination w as more often seen and of greater magnitude in individuals who display ed a T cell proliferative response to vaccine antigens at baseline and in those who mounted a significant serologic response after vaccinati on. The fold increase in viremia, as well as the rates of increase of HIV-1 in plasma after vaccination and rates of viral decline after pea k viremia, were higher in individuals with higher CD4(+) T cell counts . These data indicate that important aspects of the host-virus relatio nships underlying HIV-1 infection may be gleaned from the careful anal ysis of interventions that perturb, either positively or negatively, t he steady-state equilibrium of virus replication in vivo. The potentia l adverse consequences of vaccine-induced activation of HIV-1 replicat ion deserve consideration in formulating guidelines for immunization o f HTV-1-infected individuals. als. Given the demonstrated ability of a ntigenic challenge to activate virus replication in infected individua ls, the contribution of immune stimulation to T cell depletion and dis ease progression in HIV-1-infected individuals are important topics fo r future study.