Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients.
BACKGROUND
The presence of HIV-1 preintegration reservoir was assessed in an in vitro experimental model of latent HIV-1 infection, and in patients treated or not with highly active antiretroviral therapy (HAART).


RESULTS
In resting CD4+ T lymphocytes latently infected in vitro with HIV-1, we demonstrated that the polyclonal activation induced a HIV-1 replication, which could be prevented by the use of an HIV-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 confirm that our experimental approach allows the characterization of a functional unintegrated HIV-1 reservoir. We then explored the preintegration reservoir in HIV-1-infected patients. This reservoir was detected in 11 of 12 untreated patients, in 4 of 10 sustained responders to HAART, and in one incomplete responder. This reservoir was also inducible, labile, and anti-HIV-1 integrase drug inhibited 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 sustained responders to HAART harboring a preintegration reservoir.


CONCLUSIONS
This preintegration phase of HIV-1 latency could be a consequence of the ongoing viral replication in untreated patients and of a residual viral replication in treated patients.
Petitjean
Gaël
G
Laboratoire de Virologie, Hôpital Lapeyronie, Avenue du Doyen Gaston Giraud, 34295 Montpellier, France. gael.petitjean@gmail.com
Al Tabaa
Yassine
Y
Tuaillon
Edouard
E
Mettling
Clement
C
Baillat
Vincent
V
Reynes
Jacques
J
Segondy
Michel
M
Vendrell
Jean Pierre
JP
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D004279:DNA, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D014775:Virus Activation; D016662:Virus Integration; D017735:Virus Latency; D014779:Virus Replication
D019380:Anti-HIV Agents; D004279:DNA, Viral