Over the Rooftops of Time: Jewish Stories, Essays, Poems

AIDS: Latency and HIV Reservoirs: In the Dark Backward and Abysm of Time

AIDS: Latency and HIV Reservoirs In the Dark Backward and Abysm of Time Prospero, in Shakespeare’s The Tempest, inquires of his daughter Miranda what she remembers of her hidden past: “What seest thou else/ In the dark backward and abysm of time?” Thus does Prospero proceed to fill in the silence, telling how they came to reside on an island, of twelve years lived in an apparent time-out from the ways of the world and the conspiratorial nature of its inhabitants. Shakespeare’s metaphor for latency has its counterparts in all of nature. We speak in botanical terms of buds whose flowers are not yet manifest, or in embryology of the limb buds that will give way to our arms and legs. We speak of hidden character , of dormancy, of latent energy potential; in disease, of the incubation period between initial exposure and expression of 1 0 6 symptoms; in psychological terms of that swinging bridge (called the latency period) between temporary resolution of the oedipal struggles and the onset of puberty, a time of immense cognitive development in children. So with AIDS, it had been thought that the human immunodeficiency virus entered a state of latency that accounted for up to a decade of subclinical infection in some patients and that it was through later activation of the virus that acute disease processes became manifest. But what, in fact, had been going on during the apparent quiescence of the virus? Had HIV been incorporated into the host genome and independent replication ceased? To all intents and purposes the virus disappeared from peripheral T cells. It was not difficult to measure the presence of the HIV virus in the blood, but far more difficult to detect its presence in the lymph tissue. It turns out that ninety-eight percent of the virus is harbored there, and it now appears that the establishment of the virus in the lymph tissue occurs early in the course of the disease, even if treatment with a fourdrug combination including a protease inhibitor is begun early. At the World AIDS Conference in 1998, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, discussed the importance of diminishing these latent pools of HIV virus, of finding ways to flush out the virus in lymph tissue. The knowledge of HIV latency offers an understanding for why, when multiple-drug therapies are withdrawn, the “rebound” effect of the virus is so rapid and so potent. Therapeutic strategies must take into account this reservoir of protein-coated virus present in the lymph nodes and the potential of this virus to infect circulating CD4⫹ T cells. The effective duration of drugs used to inhibit or disrupt portions of the life cycle of the virus is one factor . Immune therapies must target viral complexes on follicular dendritic cells in lymph tissue without causing the cells to become infected. The case for early intervention seems more pointed here in delaying a firm foothold by the virus in the lymphoid tissues. As in Prospero’s seeming reprieve from the world in The Tempest, the latency period in HIV infection is anything but quiescent. From the virus’s point of view there is much work to be done. If we are essential survival machines directed by the selfish genes, as Richard Dawkins would have it, necessary for housing a virus and carrying out its instructions in the case of HIV, perhaps the virus has outsmarted itself, for in LIFE, THE UNFINISHED EXPERIMENT 1 0 7 the act of finishing us off, it has done itself in as well. True, the reader might argue, but the virus survives quite well in the large pool of those afflicted. On the other hand, we might just find a way to put the virus to work for us, as vehicle for redirecting our genetic machinery in useful and unforseen ways. 1 0 8 OVER THE ROOFTOPS OF TIME ...