Transient viral replication during analytical treatment interruptions in SIV infected macaques can alter the rebound-competent viral reservoir |
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| Authors: | Taina T Immonen Christine M Fennessey Leslie Lipkey Abigail Thorpe Gregory Q Del Prete Jeffrey D Lifson Miles P Davenport Brandon F Keele |
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| Institution: | 1. AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, Maryland, United States of America;2. Infection Analytics Program, Kirby Institute for Infection and Immunity, University of New South Wales, Sydney, New South Wales, Australia;University of Pennsylvania, UNITED STATES |
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| Abstract: | Analytical treatment interruptions (ATIs) of antiretroviral therapy (ART) play a central role in evaluating the efficacy of HIV-1 treatment strategies targeting virus that persists despite ART. However, it remains unclear if ATIs alter the rebound-competent viral reservoir (RCVR), the virus population that persists during ART and from which viral recrudescence originates after ART discontinuation. To assess the impact of ATIs on the RCVR, we used a barcode sequence tagged SIV to track individual viral lineages through a series of ATIs in Rhesus macaques. We demonstrate that transient replication of individual rebounding lineages during an ATI can lead to their enrichment in the RCVR, increasing their probability of reactivating again after treatment discontinuation. These data establish that the RCVR can be altered by uncontrolled replication during ATI. |
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