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HIV May Rebound from Latent Cells in Treatment Break

Punctuated antiretroviral therapy appears to create sustained viral evolutionary 'bottleneck'

WEDNESDAY, Oct. 22 (HealthDay News) -- In patients with HIV undergoing interruption of long-term combination antiretroviral therapy, the rebounding virus appears to originate from reactivation of latently infected cells instead of viral lineages that are continuously replicating at low levels, according to research published online Oct. 20 in the Proceedings of the National Academy of Sciences Early Edition.

Beda Joos, Ph.D., of the University Hospital Zurich, Switzerland, and colleagues analyzed data from 20 patients with HIV-1 undergoing multiple structured treatment interruptions. The researchers analyzed patients' HIV sequences to track the viral evolution, made a phylogenetic tree for each patient and determined the most recent common ancestral sequence for each patient.

The results suggest that rebounding virus during the treatment interruption does not come from viruses undergoing low-level persistent replication during therapy, the authors write. During two-week interruptions, the virus populations that emerged were relatively homogeneous, suggesting they had a monoclonal or oligoclonal origin. This indicates that the viral rebound is due to reactivation of latent cells, as opposed to persistent low-level replication, the researchers explain.

"Expansion of distinct lineages at different structured treatment interruptions suggests stochastic reactivation of different clones of long-lived latently infected cells rather than expansion of populations of low-level replicating virus. A prolonged delay in restoration of pretreatment viral diversity after treatment interruption demonstrates a surprisingly sustained evolutionary bottleneck induced by punctuated antiretroviral therapy. These data suggest that combination antiretroviral therapy introduced significant effects on further evolution of the viral population," Joos and colleagues conclude.

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