Vaccination may be key for true elimination of HIV-1

In what may prove to be a major step forward for the treatment of HIV-1 infection, scientists have discovered an effective way to eliminate a notoriously persistent form of the virus that does not respond to current therapies. The research, published online by Cell Press on March 8th from the journal Immunity, describes a vaccination strategy that may be essential for successful eradication efforts and should therefore be considered for future clinical trials.

Current antiretroviral therapies suppress the ability of HIV-1 to copy itself, but they cannot completely eliminate the virus. Under these treatment conditions, HIV-1 enters a silent, or "latent", state that rapidly becomes active again as soon therapy is stopped. "Because of the stability of latent HIV-1 inside of infected T cells, lifelong antiretroviral therapy is required, raising concerns about adverse affects over decades of therapy, the evolution of resistance, and the financial burden of treatment," explains senior study author, Dr. Robert F. Siliciano, from the Johns Hopkins University School of Medicine. "Therefore, there is an urgent need for strategies to eradicate HIV-1 from infected individuals."

Previous research has suggested that reactivation of the latent HIV-1 is an important first step for complete elimination of the virus, but it is not clear whether the activated virus or the host immune response will then lead to elimination of the infected cells. In the current study, Dr. Siliciano and colleagues observed that infected T cells survived after the latent virus was reactivated. However, when the immune response of the host T cells was heightened before the virus was reactivated, the infected cells were efficiently eliminated.

"Our results suggest that reactivation of latent HIV-1 will not purge the latent viral reservoir and that stimulation of HIV-1-specific T cell responses prior to virus reactivation may be essential for viral eradication," concludes Dr. Siliciano. "Therefore, an appropriately timed vaccination that boosts the response of the immune system to HIV-1 may be critical for therapies that move beyond suppression of HIV-1 to true elimination."

Shan et al.: "Stimulation of HIV-1-specific cytolytic T-lymphocytes facilitates elimination of latent viral reservoir after virus reactivation."

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