1st International AIDS Society Conference on HIV Pathogenesis and Treatment Buenos Aires, Argentina - July 8-11, 2001

[ABSTRACT:] To understand the dynamics of HIV replication in vivo, we used potent antiviral drugs to perturb the equilibrium between the virus and the host. Careful analyses of the viral decay following effective treatment revealed that virions are cleared rapidly with a half life of ~30 minutes and that productively infected CD4 T cells turn over briskly with a half life of <1 day. We also determined that HIV would undergo ~250 generations per year in an infected individual. These kinetic measurements convincingly demonstrate that HIV replication in vivo is not only highly dynamic, but also persistently active. These basic findings have, in turn, profound clinical implications for our therapeutic strategy against HIV: 1) monotherapy is doomed to fail because of the rapid emergence of drug-resistant virus, and 2) combination treatment that forces HIV to make multiple mutations simultaneously may be quite effective. Indeed, it has become possible to effectively control HIV replication with the use of drug combinations. Lowering the virus to undetectable levels was readily achieved, leading to marked reduction in AIDS-associated mortality in countries where these therapies are widely available. However, HIV has not been eradicated from any patient for at least two main reasons. First, the virus can lay dormant within resting memory CD4 T cells, creating a latent reservoir that decays slowly during treatment with currently available drug regimens. Second, recent experiments show that HIV replication has not been completely stopped, and the virus continues to replicate despite undetectable viremia. Attempting to overcome these obstacles, we have designed and tested a new drug regimen (lopinavir/ritonavir, efavirenz, lamivudine and tenofovir) that has resulted in a substantially faster decay of plasma viremia in treated individuals. These new data suggest that the potency of current antiretroviral regimens could be improved significantly.

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