IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART

The persistence of HIV-1 in virally suppressed infected individuals on highly active antiretroviral therapy(HAART) remains a major therapeutic problem. The use of cytokines has been envisioned as an additionaltherapeutic strategy to stimulate latent proviruses in these individuals. Immune activation therapy using IL-2has shown some promise. In the present study, we found that IL-7 was significantly more effective at enhancingHIV-1 proviral reactivation than either IL-2 alone or IL-2 combined with phytohemagglutinin (PHA) inCD8-depleted PBMCs. IL-7 also showed a positive trend for inducing proviral reactivation from resting CD4+T lymphocytes from HIV-1–infected patients on suppressive HAART. Moreover, the phylogenetic analysesof viral envelope gp120 genes from induced viruses indicated that distinct proviral quasispecies had beenactivated by IL-7, as compared with those activated by the PHA/IL-2 treatment. These studies thus demonstratethat different activators of proviral latency may perturb and potentially deplete only selected, specificportions of the proviral archive in virally suppressed individuals. The known immunomodulatory effects ofIL-7 could be combined with its ability to stimulate HIV-1 replication from resting CD4+ T lymphocytes, inaddition to other moieties, to potentially deplete HIV-1 reservoirs and lead to the rational design of immuneantiretroviralapproaches.