WASHINGTON -- Frustrated by the failure to control replication of HIV, many researchers are now focusing on host response, Judith Lieberman of the New England Medical Center in Boston said Tuesday at the First National Conference on Human Retroviruses and Related Infections here.
There probably is a balance between the virus' ability to replicate itself and an immune system's capacity to control the virus, she said. But after a decade or so, "something upsets the balance, and the virus gets the upper hand."
Antibody-based vaccines have prevented infection, but mouse studies have shown that once a virus gains a foothold, T cells are key to controlling infection, said Lieberman.
In the course of HIV, T cells remain present in asymptomatic patients, but disappear precipitously just prior to emergence of opportunistic infections.
In a phase I/II trial, Lieberman has begun transfusing virus- specific cytotoxic T cells into patients with CD4 counts of 100 to 400. Early results on five patients are grounds for some optimism. One patient's T cells gained the ability to recognize gag and an improved capacity to recognize env.
Although the quantity of virus in circulating peripheral blood monocytes remained constant in two patients (even while CD4 increased dramatically in one of them), one patient's viral titer dropped from 30 to three, and after six months the virus was no longer detectable. Another patient's titer dropped from 174 to 1.8, and then remained constant for two months at 16.2. Titer was measured in infectious units per million cells.
"If you don't have good T cell recognition, you may get a very blunted memory response, and a blunted CD8 response, and you may not recognize the full B cell repertoire that could be developed, because you are lacking the T cell," Deborah Birx, a researcher at Walter Reed Army Institute of Research in Rockville, Md., told BioWorld.
Birx presented her own research as well as some related studies on T cell immunity. She and Bill Blattner of the National Cancer Institute are examining three laboratory workers who became infected with a known strain of HIV, 3b. All three were vaccinated with 3b products, MicroGeneSys Inc.'s gp160, and Genentech Inc.'s 3b gp120, and all three of their immune systems recognized both immunogens.
"We don't know what the clinical relevance is, but as we study these patients and their clinical outcome, we will be able to investigate the relevance of these specific T cell responses," Birx told BioWorld.
Earlier this year, Jonas Salk reported in Berlin that his vaccine had reduced viral burden in patients he studied by about half a log, on average, and had augmented CD4 counts, said Birx.
This research is in its infancy, she said, and "we are probably five to six years from hard clinical end points from any trial." She compared the state of the art with the early days of allergy research, when researchers had ground up whole hymenopterans to vaccinate patients against anaphalaxis. It took 20 years to find the antigen, she said.
"I don't think we should get discouraged," said Birx, echoing Richard Koup of the Aaron Diamond AIDS Research Center the previous day. "I think we should just do the immunology."
-- David C. Holzman Washington Editor
(c) 1997 American Health Consultants. All rights reserved.