AIDSWEEKLY Plus, 20 May 1996 issue; Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588
Daniel J. DeNoon, Senior Editor

New data refute popular hypotheses of AIDS pathogenesis and point to the immune system as the most important means of controlling HIV.

HIV has an extraordinary ability to mutate into new quasispecies within an infected individual. This observation has led many researchers to conclude that the characteristic loss of CD4(+) T lymphocytes in AIDS occurs when the increasing antigenic diversity of HIV quasispecies overwhelms the immune system (Nowak et al., Science, 1991;254:963).

But extensive study of six individuals - two with rapid CD4 decline, two with slow CD4 decline, and two with stable CD4 counts - shows that it is the stable patients who have the greatest viral diversity.

Northwestern University researcher Steven M. Wolinsky and colleagues reported the findings in the journal Science ("Adaptive Evolution of Human Immunodeficiency Virus-Type 1 During the Natural Course of Infection," Science 1996;272(5261):537-542)

"These data suggest that a rapid decline in the CD4 T-cell count can occur when an HIV-1-specific immune response is deficient and a predominant viral form with great pathogenic potential is lacking," Wolinsky et al. wrote.

"The presence of diverse viral forms at a given time point may reflect the length of time after primary infection, or shifts in the viral population possibly related to survival advantage during changes in the host environment (for example, a vigorous cell-mediated immune response or a change in cell tropism)."

Wolinsky et al. found that all six of their subjects had relatively stable virus populations for about nine months after they first acquired HIV infection.

The two patients with rapid progression of HIV disease maintained relatively homogeneous virus populations throughout their infection, even when their CD4 counts precipitously dropped.

But at late time points in the study, the two patients with the greatest diversity of viral quasispecies had stable CD4 counts.

When Wolinsky et al. examined the phenotypic properties of the viruses from their six subjects, they found that none had the syncytium-inducing form previously associated with disease progression. Viruses from all six subjects replicated and depleted CD4 cells to an equal extent in the SCID-Hu mouse model.

The researchers then assessed the anti-HIV immune responses of their six subjects. Unlike studies of simian immunodeficiency virus (SIV) in macaques, there was no clear- cut association between the appearance of neutralizing antibody responses and progression to AIDS.

However, they found that the rate of disease progression in their subjects had a strong inverse correlation to the frequency of cytotoxic lymphocyte (CTL) precursors.

"Thus, a vigorous HIV-1-specific HLA class I-restricted CTL response was associated with slow rather than rapid rates of development of disease, contrary to the prediction that the immunopathogenic effects of CTLs are responsible for depletion of CD4 T cells," Wolinsky et al. concluded.

In a commentary article, Frank Miedema and Michel R. Klein of the Netherlands Red Cross Blood Transfusion service said that the findings show that sustained CTL responses are needed to fight HIV ("AIDS Pathogenesis: A Finite Immune Response to Blame?" Science 1996;272(5261):505-506).

They argued that while antiretroviral agents may eliminate free HIV from the blood, they do not directly effect HIV infected cells.

"Large numbers of productively infected cells, not free virus in blood, will harm the immune system the most," they wrote.

"Therefore, efficient control of the number of HIV-1- infected cells is of utmost importance. HIV-1 may be best contained by combination immunotherapy with antiviral drugs."

The corresponding author for the Wolinsky et al. study is Steven M. Wolinsky, Department of Medicine, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois 60611.

The corresponding authors for the commentary article are Frank Miedema and Michel R. Klein, Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Plesmanlaan 125, 1066 CX Amsterdam, Netherlands. Email: clbkvi@xs4all.nl.

Copyright (c) 1995 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.

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Copyright © 1996 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.