Persistence of viral HLA-DR- CD4 T-cell reservoir during prolonged treatment of HIV-1 infection with a five-drug regimen |
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Authors: | van Rij Ronald P van Praag Rieneke M E Prins Jan M Rientsma Ronald Jurriaans Suzanne Lange Joep M A Schuitemaker Hanneke |
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Institution: | Department of Clinical Viro Immunology, CLB/Sanquin and Landsteiner Laboratory of the Academic Medical Center, Amsterdam, The Netherlands. |
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Abstract: | During sustained suppression of plasma viraemia using a standard triple-drug regimen, replication-competent HIV-1 can still be recovered from resting memory CD4 T cells. In an attempt to accelerate the clearance of this pool of infected CD4 T cells, eight antiretroviral therapy-naive HIV-1-infected patients were treated with a five-drug regimen. While plasma HIV-1 RNA levels generally remained below the level of detection (< 5 copies/ml), replication competent HIV-1 was isolated from HLA-DR- CD4 T cells from all patients on multiple occasions throughout treatment. Decay slopes of infected CD4 T cells ranged from -0.061/week (half-life=2.6 months) to +0.003/week (half-life = infinite). Virus was still detectable at the last time point analysed (80-173 weeks) in all patients. Although more intensive treatment results in improved suppression of plasma viraemia compared with standard drug regimens, it does not result in clearance of the viral reservoir in this timeframe. Strategies other than treatment with a combination of five of the currently available drugs need to be pursued in order to achieve eradication of HIV-1 from this cellular reservoir. |
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