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Ongoing HIV dissemination during HAART

Nature Medicine volume 5, pages 1099–1104 (1999)Cite this article

Multiphasic HIV decrease in individuals treated with anti-retroviral drugs has been modeled as the independent decay, with different half-lives, of distinct pools of cells infected before the initiation of treatment. We analyzed the kinetics of plasma HIV RNA in individuals receiving combinations of up to five drugs. The initial rates of decline increased substantially with the efficacy of treatment. Decline rates decreased with time, approaching zero in some cases. These observations are better explained if most of the virus is produced by cells infected after the initiation of therapy. Accordingly, treatment results in ongoing HIV infection cycles of decreasing amplitude, but the decrease progressively attenuates and may cease altogether at some viral load. We propose that HIV replication occurs in multiple local bursts, associated with immune activation in response to antigens. Current anti-retroviral drugs substantially reduce the size of these bursts and diminish their frequency but fail to abolish them.

The infected-cell half-life model

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Figure 1: Plasma HIV RNA first-week decrease with four-drug combination therapy.
Figure 2: HIV RNA decay rate constants for one-, three- and five-drug regimens; the means of individual decay rate constants were calculated for 16, 15 and 9 patients, respectively.
Figure 3: Linking HIV production to immune activation.
Figure 4: HIV RNA decrease with a four-drug combination therapy.

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Acknowledgements

We thank S. Danner, J. Metcalf, B. Mueller, P.A. Pizzo, G.-J. Waverling and C. Yoder for their contribution to the clinical trials and for making patient data available for analysis. We thank S.Livnat for reading and improving the manuscript.

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Authors and Affiliations

  1. Office of AIDS Research, National Institutes of Health, Bethesda, Maryland, USA

    Zvi Grossman

  2. Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Israel

    Zvi Grossman

  3. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Michael Polis

  4. Center for AIDS Research, Emory University, Atlanta, Georgia, USA

    Mark B. Feinberg

  5. Virology Institute Sheba Medical Center, Tel Hashomer, Israel

    Zehava Grossman

  6. Department of Infectious Diseases Sheba Medical Center, Tel Hashomer, Israel

    Itschak Levi

  7. HIV and AIDS Malignancy Branch, National Cancer Institute National Institutes of Health, Bethesda, Maryland, USA

    Shirley Jankelevich & Robert Yarchoan

  8. Laboratory of Experimental and Computational Biology, Frederick Cancer Research Center, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA

    Jacob Boon & Dimiter S. Dimitrov

  9. Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Holland

    Frank de Wolf & Jaap Goudsmit

  10. Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Holland

    Joep M.A. Lange

  11. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    William E. Paul

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Correspondence to Zvi Grossman.

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Grossman, Z., Polis, M., Feinberg, M. et al. Ongoing HIV dissemination during HAART. Nat Med 5, 1099–1104 (1999). https://doi.org/10.1038/13410

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