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Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy

Abstract

Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection. However, HIV-1 can persist in a latent form in resting CD4+ T cells. We measured the decay rate of this latent reservoir in 34 treated adults whose plasma virus levels were undetectable. The mean half-life of the latent reservoir was very long (43.9 months). If the latent reservoir consists of only 1 × 105 cells, eradication could take as long as 60 years. Thus, latent infection of resting CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective anti-retroviral therapy.

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Figure 1: Frequency of latently infected cells in 34 HIV-1-infected adults on combination therapy who had plasma virus levels less than 200 copies/ml.
Figure 2: Decay rates of the latent reservoir in individual patients.
Figure 3: Mean rate of decay of the latent reservoir.

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Acknowledgements

We thank C. Raines, S.Barnett, B. Perdue-Sabundayo and J. Keruly for coordinating patient visits and help with data analysis. We also thank L. Carruth, J. L'Esperance and C. Murray for help with the experiments. We thank Y. Afacan for providing patients and R. Brookmeyer for advice on statistical analysis of decay rates. This work was supported by NIH grant AI43222 to R.F.S.

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Finzi, D., Blankson, J., Siliciano, J. et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 5, 512–517 (1999). https://doi.org/10.1038/8394

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