AIDSWEEKLY Plus, 19 August 1996
Daniel J. DeNoon, Senior Editor

The hallmark of HIV disease is a marked decrease in CD4(+) T cells. Antiretroviral therapies have long been evaluated in terms of their ability to reverse this trend.

But the new data suggest that clinicians will have to measure more than mere numbers to determine whether a patient's immune system has improved.

"An increase in T-cell counts is not necessarily associated with an increase in T-cell functional capacity," said Nadine G. Pakker of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.

Pakker spoke during a presentation to the XI International Conference on AIDS, held July 7-12, 1996 in Vancouver, British Columbia, Canada.

Pakker and colleagues evaluated CD4(+) and CD8(+) T-cell counts and T-cell reactivity to CD3 monoclonal antibody in HIV infected patients receiving antiretroviral monotherapy.

Ten of the patients received the protease inhibitor ritonavir, nine patients received the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine, 10 patients received the nucleoside analog reverse transcriptase inhibitor zidovudine (AZT), and 11 patients were untreated.

The researchers found that the patients' baseline T-cell functional capacity correlated with their CD4(+) T-cell counts.

"The functional capacity ... is in the same range as the percentages of CD4 counts," Pakker said. "This indicates that the person who has 10 percent of normal CD4 count also has about 10 percent of the functional capacity of his immune system left."

The patients receiving ritonavir had the most pronounced and sustained rise in CD4 counts. During the first four weeks of ritonavir monotherapy these patients had a steep decline in viral load followed by a return to baseline values.

Changes in T-cell function were inversely correlated with changes in viral load.

In the patients receiving AZT or nevirapine, increases in CD4 counts were not accompanied by increases in T-cell function.

"During therapy, T cells can become less functional," Pakker said. "This can best be explained by the selective outgrowth of a T-cell subpopulation of nonresponsive T cells."

She suggested that evaluation of antiretroviral therapy should include measures of immune function.

"The outcome of therapy will be dependent on virological markers as well as the ability of [a drug to induce] immune reconstitution, both qualitative and quantitative," Pakker said. "Detailed analysis of the phenotype and function of the repopulating T cells are required to further address this issue."

960819
AW960811

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 http://www.newsrx.net

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.