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The reason why antiviral therapy can't annihilate HIV infection, and what to do about it

Antiviral therapy has been used to suppress HIV replication and has dramatically improved the clinical course of disease in affected patients. But the existence of viral reservoirs precludes the complete elimination of HIV from treated patients. In a new study appearing on November 1 in The Journal of Clinical Investigation, Tae-Wook Chun and colleagues from the NIH offer new insight into the eradication of HIV in infected individuals receiving antiviral therapy.

The authors focused on HIV-infected patients who had received effective antiviral therapy for extended periods of time and examined the nature of their residual virus as well as the underlying mechanisms of viral persistence. They demonstrate that HIV persists in both resting and activated CD4+ T cells of patients having received up to 9.1 years of effective antiviral therapy with undetectable levels of HIV in their plasma.

Their data also suggest that latently infected, resting CD4+ T cells may become reactivated, most likely as a result of normal immunologic responses to various antigens and cytokines. In turn, virions released during the reactivation process may spread to neighboring resting as well as activated CD4+ T cells; direct cell-to-cell spread in the absence of virion release may also occur.

The study could impact the design of future therapies aimed at eradicating HIV in patients who have received effective antiviral therapy for extended periods of time. Considering that reactivation of latently infected, resting CD4+ T cells contributes to the persistence of HIV and initiation of new infection cycles, co-administration of an effective and safe reagent that is capable of dampening cellular activation could minimize the spread of virions to uninfected bystander cells.


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Source:Journal of Clinical Investigation


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