HIV Persists in Aged Memory CD4 Cells during 8 Years of Effective HAART Effective HAART often reduces plasma HIV RNA levels below the limit of detection, but a latent replication-competent HIV reservoir remains present within CD4 T-lymphocytes. The persistence of this reservoir is a consequence of the long lifespan of these cells, and possibly low levels of viral replication. As reported at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, taking place this week in San Francisco, researchers in the Netherlands investigated the amount of viral replication in patients on long-term successful HAART. They studied the evolution of reverse transcriptase (RT) and protease proviral DNA sequences and the development of drug resistance mutations; in addition, they determined viral reservoirs after 8 years of treatment. The study included 9 patients who had been on HAART 8 years, with plasma HIV RNA levels below 50 copies/mL. Peripheral blood mononuclear cells (PBMCs) were obtained before and during antiretroviral treatment. HIV DNA and RNA levels were assessed using Taqman real-time PCR, and proviral HIV RT and protease genes were sequenced. Naive (CD27+ CD45RO-), memory (CD45RO+ CD57-), and aged memory (CD45RO+ CD57+) CD4 T-cells were obtained by flow cytometry after 8 years of therapy. Results
Conclusion Based on these results the authors concluded, "The absence of a decline in viral DNA load in combination with a reduction in viral RNA load suggest persistence of proviral HIV in a stable latent HIV reservoir. Flow cytometric analysis did suggest that proviral DNA is becoming part of normal T-cell homeostasis explaining the high level of HIV DNA in aged memory cells." "The lack of drug-resistance mutations under continued drug pressure indicates absence of viral replication for up to 8 years," they added. "Indeed, viral evolution could not be detected in all 9 patients." University Medical Center, Utrecht, the Netherlands. 09/29/06 Reference
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Total levels of proviral HIV DNA in PBMCs before and after 8 years of HAART were
similar. 
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FDA-Approved
Protease
Inhibitors |