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

Diana Finzi; Joel Blankson; Janet D. Siliciano; Joseph B. Margolick; Karen Chadwick; Theodore Pierson; Kendall Smith; Julianna Lisziewicz; Franco Lori; Charles Flexner; Thomas C. Quinn; Richard E. Chaisson; Eric Rosenberg; Bruce Walker; Stephen Gange; Joel Gallant; Robert F. Siliciano

doi:10.1038/8394

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

Diana Finzi, Joel Blankson, Janet D. Siliciano, Joseph B. Margolick, Karen Chadwick, Theodore Pierson, Kendall Smith, Julianna Lisziewicz, Franco Lori, Charles Flexner, Thomas C. Quinn, Richard E. Chaisson, Eric Rosenberg, Bruce Walker, Stephen Gange, Joel Gallant, Robert F. Siliciano

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1624 Scopus citations

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 x 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.

Original language	English (US)
Pages (from-to)	512-517
Number of pages	6
Journal	Nature medicine
Volume	5
Issue number	5
DOIs	https://doi.org/10.1038/8394
State	Published - May 1999

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1038/8394

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Finzi, D., Blankson, J., Siliciano, J. D., Margolick, J. B., Chadwick, K., Pierson, T., Smith, K., Lisziewicz, J., Lori, F., Flexner, C., Quinn, T. C., Chaisson, R. E., Rosenberg, E., Walker, B., Gange, S., Gallant, J., & Siliciano, R. F. (1999). Latent infection of CD4⁺ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nature medicine, 5(5), 512-517. https://doi.org/10.1038/8394

Finzi, D, Blankson, J , Siliciano, JD , Margolick, JB, Chadwick, K, Pierson, T, Smith, K, Lisziewicz, J, Lori, F, Flexner, C, Quinn, TC, Chaisson, RE, Rosenberg, E, Walker, B, Gange, S, Gallant, J & Siliciano, RF 1999, 'Latent infection of CD4⁺ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy', Nature medicine, vol. 5, no. 5, pp. 512-517. https://doi.org/10.1038/8394

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title = "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 x 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.",

author = "Diana Finzi and Joel Blankson and Siliciano, {Janet D.} and Margolick, {Joseph B.} and Karen Chadwick and Theodore Pierson and Kendall Smith and Julianna Lisziewicz and Franco Lori and Charles Flexner and Quinn, {Thomas C.} and Chaisson, {Richard E.} and Eric Rosenberg and Bruce Walker and Stephen Gange and Joel Gallant and Siliciano, {Robert F.}",

note = "Funding Information: Acknowledgments 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{\textquoteright}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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AU - Margolick, Joseph B.

AU - Chadwick, Karen

AU - Pierson, Theodore

AU - Smith, Kendall

AU - Lisziewicz, Julianna

AU - Lori, Franco

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AU - Chaisson, Richard E.

AU - Rosenberg, Eric

AU - Walker, Bruce

AU - Gange, Stephen

AU - Gallant, Joel

AU - Siliciano, Robert F.

N1 - Funding Information: Acknowledgments 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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Latent infection of CD4⁺ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy

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