Mechanism of HIV persistence: implications for vaccines and therapy.

Periodic infusion of autologous HIV-antigen presenting cells (APCs), that stimulate the cytotoxic (CTL) response, while being incapable of producing virus, should lower viral burden and boost CD4+ count in HIV-seropositive individuals. Viral burden reasserts itself after antiviral therapy ceases or is interrupted for long. Therapy, therefore, would have to continue for life.

AIDS as immune system activation. Key questions that remain.

Immune system activation is gaining attention as a central part of HIV pathogenesis. Although there is no consensus yet as to the source of the signal or the result of the signalling, this line of thinking represents a significant shift in the paradigm away from considering HIV disease like any other cytopathic viral infection. Hopefully, completion of studies focussed on this approach will lead to more complete understanding of AIDS and more effective therapies, and will at least bring to the fore some of the central unanswered questions in modern cellular immunology.

Mathematical models of HIV infection. I. Threshold conditions for transmission and host survival.

This is the second in a series of papers modeling human immunodeficiency virus (HIV) infections at four levels: transmission, interaction with the immune system, gene regulation, and selection of mutants. In the previous paper (1) we described and presented a theory of the HIV cytopathic effect based upon the models (and a review of the literature). In this article we give mathematical equations of threshold conditions that connect infectivity, length of host survival, and frequency of acts conducive to transmission.

The HIV cytopathic effect: potential target for therapy?

HIV kills activated infected CD4+ T cells after a burst of replication and the release of large numbers of virions. From a review of the literature on HIV regulatory genes and from preliminary mathematical models of HIV dynamics at four levels (host population epidemiology, the immune system, gene regulation within infected cells, and selection of mutants) we have arrived at the theory that in the etiology of HIV the HIV cytopathic effect may actively be caused by a viral regulatory gene product. The most likely candidate is the rev regulatory protein.