Localized or systemic in vivo heat inactivation of human immunodeficiency virus (HIV): a mathematical analysis.
Temperatures > or = 42 degrees C, maintained for > or = 25 min, inactivate approximately 25% of human immunodeficiency virus (HIV). HIV-infected T cells are more sensitive to heat than healthy lymphocytes, and susceptibility increases when the cells are presensitized by exposure to tumor necrosis factor. Thus, induction of a whole-body hyperthermia or hyperthermia specifically limited to tissues having a high viral load is a potential antiviral therapy for acquired immunodeficiency syndrome (AIDS). Accordingly, we incorporated therapeutic hyperthermia into an existing mathematical model that evaluates the interaction between HIV and CD4+ T cells. Given the assumptions and limitations of this model, the results indicate that a daily therapy lowering the population of actively infected cells by 40% or infectious virus by 40% would effectively reverse the depletion of T cells. In contrast, a daily decline of 20% of either actively infected cells or infectious virus would have a marginal effect. However, daily reduction by 20% of both actively infected cells and infectious virus could restore T-cell numbers, assuming that permanent damage had not been inflicted on the thymus. Since daily treatments would probably be excessively stressful, whole-body hyperthermia seems unlikely to be clinically useful. In contrast, heating directed specifically to areas of viral concentration may be effective and have a suitable risk/benefit ratio.
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Lawrence Berkeley Laboratory, University of California 94720.
Perelson
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Nelson
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Sessler
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D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D015658:HIV Infections / Q000628:therapy / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced; D008212:Lymphocyte Depletion; D008954:Models, Biological