HIV May Replicate Faster Than Thought

Spanish researchers studying HIV replication dynamics and protease inhibitor (PI) efficacy in culture observe that the virus replicates at a much higher rate than is currently believed to be the case.

This finding, Dr. Jose Alcami from the Instituto de Salud Carlos III in Madrid told Reuters Health, has "important implications" for antiretroviral therapy.

Dr. Alcami and colleagues transfected lymphocytes from normal donors with a plasmid containing an infectious full-length HIV DNA clone.

In the system, he said, "HIV DNA is directly introduced into the cell nucleus, bypassing the early steps of the HIV cycle -- entry, decapsidation, retrotranscription, nuclear transport and probably integration."

The results showed that HIV reactivation from the state of proviral DNA was faster than previously estimated. "In 2 hours, we detected intracellular expression of viral proteins and infectious viral particles outside the cell in 6-8 hours. Therefore, a full HIV cycle could be as fast as 9-12 hours - -50% of previously estimated."

This new information on HIV kinetics has "important consequences" regarding the efficacy of antiretroviral drugs, particularly PIs, which target post-integration steps, Dr. Alcami added.

For example, by adding ritonavir (Norvir) at different times to HIV-infected lymphocytes, the researchers were able to show that continuous drug pressure by PIs is necessary to control HIV replication.

Even "a 2-hour window of low PI concentrations results in viral escape," Dr. Alcami noted. These findings, he concluded, show at the cellular level, "the absolute requirement of maintaining efficient levels of protease inhibitors in HIV-treated patients to control viral replication."

09/09/04

J Med Virol 2004;73:502-507.