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Abstract:
Quantification of HIV-l replication and turnover in human plasma, PBMCs, and lymphoid tissues promises to provide unique insights into AIDS pathogenesis and hasten antiretroviral therapy and vaccine research efforts. HIV-1 load in vivo is comprised of cell-free virus as well as substantial numbers of replication-active, latent, or defective viral genomes, all of which likely play a role in disease pathogenesis. The dynamics of HIV-1 replication in vivo are largely unknown yet they are critical to our understanding of disease pathogenesis. Experimental drugs that are potent inhibitors of viral replication were used to show that the composite lifespan of plasma virus and virus- producing cells is remarkably short (half-life 2 days). Almost complete replacement of wild-type virus in plasma by drug-resistant variants occurred after 14-28 days, indicating that HIV-1 viremia is sustained primarily by a dynamic process involving continuous rounds of de novo virus infection, replication, and rapid cell turnover. Notwithstanding these findings, antiretroviral regimens which maximally impact all viral 'compartments' are likely to result in the greatest therapeutic gains and the longest delay in the development of drug resistance. It is thus essential to elucidate the numbers and half-lives of cell populations harboring active, latent, or defective viral forms.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 22 Jun 94-21 Jun 95 |
| Pages: |
30 |
| Report Date: |
14 JUL 95 |
| Contract Number: |
DAMD17-93-C-3146 |
| Report Number: |
A155792 |
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