Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 122, Issue 1, Pages 22-28Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2008.05.033
Keywords
HAART; latency; reservoir; antiretroviral drug; residual viremia; slope; eradication
Categories
Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NIAID NIH HHS [R01 AI043222, R01 AI051178] Funding Source: Medline
- PHS HHS [51178] Funding Source: Medline
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Although highly active antiretroviral therapy (HAART) can reduce HIV-1 viremia to levels that are below the limit of detection of clinical Assays, the virus persists in reservoirs, and trace levels of free virions can be found in the plasma. Whether this residual viremia represents ongoing cycles of replication continuing despite HAART or simply the release of virus from stable reservoirs has been controversial. Here we summarize the evidence that HAART can stop ongoing cycles of replication. The evidence comes from a detailed analysis of the residual viremia, which shows it to be archival and nonevolving in character. In addition, new pharmacodynamic measures incorporating a previously ignored slope parameter have provided the first real indication of how well HAART actually suppresses viral replication in vivo. Together, these results argue that the ultimate theoretical potential of HAART to control viral replication has already been reached. Progress toward eradication of the infection will require novel approaches to target the stable reservoirs that persist even when viral replication is completely halted.
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