Modeling plasma virus concentration during primary HIV infection.
During primary HIV infection the viral load in plasma increases, reaches a peak, and then declines. Phillips has suggested that the decline is due to a limitation in the number of cells susceptible to HIV infection, while other authors have suggested that the decline in viremia is due to an immune response. Here we address this issue by developing models of primary HIV-1 infection, and by comparing predictions from these models with data from ten anti-retroviral, drug-naive, infected patients. Applying nonlinear least-squares estimation, we find that relatively small variations in parameters are capable of mimicking the highly diverse patterns found in patient viral load data. This approach yields an estimate of 2.5 days for the average lifespan of productively infected cells during primary infection, a value that is consistent with results obtained by drug perturbation experiments. We find that the data from all ten patients are consistent with a target-cell-limited model from the time of initial infection until shortly after the peak in viremia. However, the kinetics of the subsequent fall and recovery in virus concentration in some patients are not consistent with the predictions of the target-cell-limited model. We illustrate that two possible immune response mechanisms, cytotoxic T lymphocyte destruction of infected target cells and cytokine suppression of viral replication, could account for declines in viral load data not predicted by the original target-cell-limited model. We conclude that some additional process, perhaps mediated by CD8+ T cells, is important in at least some patients.
Stafford
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MA
Computing and Mathematical Sciences Department, Texas A & M University-Corpus Christi, 6300 Ocean Drive, Corpus Christi, TX 78412, USA.
Corey
L
L
Cao
Y
Y
Daar
E S
ES
Ho
D D
DD
Perelson
A S
AS
D016207:Cytokines / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016018:Least-Squares Analysis; D018448:Models, Immunological; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication
D016207:Cytokines