How long should treatment be given if we had an antiretroviral regimen that completely blocks HIV replication?
Int Conf AIDS 1996 Jul 7-12; 11:19 (abstract no. Th.B.930) Perelson AS, Essunger P, Markowitz M, Ho DD; Aaron Diamond AIDS Research Center, New York, NY. Fax: (212) 725-1126.
After the administration of potent antiretroviral agents to inhibit de novo infection, the plasma levels of HIV-1 drop approximately 100-fold in the first two weeks due to the fast clearance of free virions and the rapid loss of productively infected cells. This initial acute decrease is then followed by a slower second-phase decay of plasma viremia. Two new mathematical models were developed and used to analyze viral load data, collected from 8 drug-naive patients following the combined administration of nelfinavir, zidovudine, and lamivudine. Fitting the data to either model, we conclude that persistent viral production by long-lived cells (e.g., macrophages) infected before the initiation of antiviral therapy can explain the second-phase decay. Likewise, the second-phase decay can also be modeled by the gradual activation of cells that latently carry infectious HIV. In either model, such cells have, on average, a lifespan of 13.3 days. Interestingly, the lifespan of either cellular compartment is directly correlated with the baseline CD4 count. Studies are now in progress to discriminate between these two models. Nevertheless, given the above lifespan plus available estimates of the pool sizes of infected macrophages and latently infected CD4 lymphocytes, we conclude that a completely inhibitory treatment regimen would need to be administered for approximately 1.5-3.0 years before each compartment burns out. This estimated duration of treatment does not consider an unforeseen slower third-phase decay or the possibility of a sanctuary site. If latently infected cells are the principal compartment contributing to the second-phase decay, it may be possible to accelerate this process by immune stimulation.
Keywords: AEGIS, HIV-1, Virus Replication, Zidovudine, Lamivudine, Anti-HIV Agents, Viral Load, Nelfinavir, CD4-Positive T-Lymphocytes, CD4 Lymphocyte Count, Reverse Transcriptase Inhibitors, HIV Protease Inhibitors, Antiviral Agents, Viremia, Virion, Human, therapy, virology, drug therapy, ICA11
