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Immune control of HIV-1 after early treatment of acute infection

Abstract

Virus-specific T-helper cells are considered critical for the control of chronic viral infections1,2. Successful treatment of acute HIV-1 infection leads to augmentation of these responses3,4,5, but whether this enhances immune control has not been determined. We administered one or two supervised treatment interruptions to eight subjects with treated acute infection, with the plan to restart therapy if viral load exceeded 5,000 copies of HIV-1 RNA per millilitre of plasma (the level at which therapy has been typically recommended) for three consecutive weeks, or 50,000 RNA copies per ml at one time. Here we show that, despite rebound in viraemia, all subjects were able to achieve at least a transient steady state off therapy with viral load below 5,000 RNA copies per ml. At present, five out of eight subjects remain off therapy with viral loads of less than 500 RNA copies per ml plasma after a median 6.5 months (range 5–8.7 months). We observed increased virus-specific cytotoxic T lymphocytes and maintained T-helper-cell responses in all. Our data indicate that functional immune responses can be augmented in a chronic viral infection, and provide rationale for immunotherapy in HIV-1 infection.

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Figure 1: HIV-1 Gag-specific T-helper-cell responses in HIV-1 infection.
Figure 2: Viral load in a pilot study of successive treatment interruptions in a 32-yr-old male with treated acute HIV-1 infection.
Figure 3: Virology and immunology in three subjects who controlled viraemia after the first treatment interruption.
Figure 4: Virology and immunology in subjects requiring repeated treatment interruption.

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Acknowledgements

This work was supported by the Doris Duke Charitable Foundation (B.D.W., E.S.R.), the NIH (E.S.R., R.D., B.D.W.), the Elizabeth Glaser Pediatric AIDS Foundation (P.J.R.G.), the Deutscher Akademischer Austauschdienst (M.A.), the UK Medical Research Council (P.J.R.G.) and several private donors. We thank A. Munoz for conducting the analysis comparing our data with the MACS data. We also thank the subjects who participated in these trials, M. S. Hirsch and D. T. Scadden for comments on the manuscript; B. Dale for supplying kits for viral load testing; P. Sax and B. Davis for help in recruiting study subjects; M. J. Ferraro, J. Eversley and S. Masci, for technical support; and B. Rawal for performing modified HIV-1 ELISA assays. P.J.R.G. is an Elizabeth Glaser Scientist and B.D.W. is a Doris Duke Distinguished Clinical Science Professor.

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Correspondence to Bruce D. Walker.

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Rosenberg, E., Altfeld, M., Poon, S. et al. Immune control of HIV-1 after early treatment of acute infection. Nature 407, 523–526 (2000). https://doi.org/10.1038/35035103

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