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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

Nature Medicine volume 5, pages 512–517 (1999)Cite this article

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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Authors and Affiliations

  1. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    Diana Finzi, Joel Blankson, Janet D. Siliciano, Theodore Pierson, Charles Flexner, Thomas C. Quinn, Richard E. Chaisson, Joel Gallant & Robert F. Siliciano

  2. Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, 21205, Maryland, USA

    Joseph B. Margolick & Karen Chadwick

  3. Department of Medicine, Cornell University Medical College, New York, 10021, New York, USA

    Kendall Smith

  4. RIGHT and Georgetown University, Washington, 20007, DC, USA

    Julianna Lisziewicz & Franco Lori

  5. National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, 20892, Maryland, USA

    Thomas C. Quinn

  6. Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Charleston, 02129, Massachusetts, USA

    Eric Rosenberg & Bruce Walker

  7. Department of Biostatistics, Johns Hopkins University School of Hygiene and Public Health, Baltimore, 21205, Maryland, USA

    Stephen Gange

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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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