Abstract
Background : The presence of HIV-1 preintegration reservoir was assessed in an in vitroexperimental model of latent HIV-1 infection, and in patients treated or not with highly activeantiretroviral therapy (HAART).Results : In resting CD4+ T lymphocytes latently infected in vitro with HIV-1, we demonstrated thatthe polyclonal activation induced a HIV-1 replication, which could be prevented by the use of anHIV-1 integrase inhibitor. We also showed that this reservoir was labile since the rescuable HIV-1-antigens production from unintegrated HIV-1 genomes declined over time. These data confirmthat our experimental approach allows the characterization of a functional unintegrated HIV-1reservoir. We then explored the preintegration reservoir in HIV-1-infected patients. This reservoirwas detected in 11 of 12 untreated patients, in 4 of 10 sustained responders to HAART, and in oneincomplete responder. This reservoir was also inducible, labile, and anti-HIV-1 integrase druginhibited its induction. Finally, this reservoir was associated with the presence of spontaneous HIV-1 antigens producing CD4+ T cells in blood from 3 of 3 untreated patients and 2 of 2 sustainedresponders to HAART harboring a preintegration reservoir.Conclusion : This preintegration phase of HIV-1 latency could be a consequence of the ongoingviral replication in untreated patients and of a residual viral replication in treated patients.