Newsday - November 15, 1996
Laurie Garrett - Staff Writer

Despite genuine breakthroughs in treatment of HIV infection - notably, triple drug combinations that knock viral levels in patients' blood down to below the limits of detection - these individuals' immune systems never recover. This finding is one of several factors that now have experts in the field convinced that the appropriate time to commence triple drug therapy is very early in HIV infection - perhaps within the first six months after exposure to the virus.

Which means that most of the estimated 75,000 to 100,000 Americans now taking protease inhibitors in combination with two other anti-HIV drugs, are unlikely to experience the optimal benefits that had been expected from the breakthrough therapies because they are already far enough along in their infections to have experienced profound immune-system damage. Despite this, most patients on combination therapy continue to experience profound decreases in HIV levels in their blood because of the drugs.

The NIH convened a panel of experts, assigned to sift through the latest - largely unpublished - data to determine the best way the currently licensed three protease inhibitors and seven other anti-HIV drugs should be used. Although the panel's findings are unlikely to be released before January, public testimony from top scientists was presented this week in Washington.

Prior to this gathering, the hope was that triple combination therapy would knock HIV levels down to undetectable points, and the patients' immune system, possibly with chemical boosting, would mop up remaining viruses. Concern about development of mutant drug-resistant strains of HIV was somewhat muted because it seemed that the drugs and patients' immune system would so thoroughly suppress HIV that it could not reproduce and thus not mutate.

But Dr. Ashley Haase of the University of Minnesota warned, "there are certainly still residue infections," in the nodes after six months of treatment.

However others, such as Luc Perrin of Geneva University Hospital in Switzerland and Dr. Martin Markowitz of the Aaron Diamond AIDS Research labortory in Manhattan, using different drug combination, have succeeded in zeroing out the virus from both patients' blood and apparently their lymph nodes. But these studies were done less than six months from initial infection.

Timing, it seems, is everything. Numerous studies indicate that after HIV has been in the body for six months, it produces irreversible damage to the immune system. For example, Angela McLean of the Institut Pasteur in Paris showed that once the immune system recognizes that HIV has invaded the body it sends massive numbers of lymphocytes called CD4 T-cells into the bloodstream battlefield. But CD4 cells are precisely what HIV is designed to invade and inside of which the virus grows.

Dr. Ronald Gress of the NIH presented further evidence drawn not from HIV patients, but from cancer cases. Unpublished NIH data drawn from hundreds of American women with breast cancer shows that chemotherapy similarly wipes out T-cells and their "specificities." Human beings fight off disease because certain types of T-cells, called memory cells, are programmed early in childhood to recognize a given enemy and respond. Gress found that treated breast cancer patients suffer permanent loss in the range of their memory capacities - what immunologists refer to as a narrowing of the T-cell repertoires.

What Gress sees in cancer patients seems to also be the case with HIV.

What may be happening, says the University of California in Los Angeles' Dr. Janis Giorgi, is that the surviving T-cells are aging at a pace far faster than normal.

The NIH's Dr. Thomas O'Brien said that these findings may explain that people who are under 30 when they get infected with HIV live, on average, far longer than their older counterparts."

Dr. Cliff Lane of the National Institute of Allergy and Infectious Diseases found in studies of 11 HIV patients in different stages of illness that the repertoire of T-cell memory gets "severely skewed" as patients get further into their disease process.

Dr. Anthony Kelleher of St. Vincent's Hospital in Sydney, Australia, showed that this skewing results in clear differences in patients' abilities to respond to such things as allergins, tetanus and standard chemicals used to test immune responses.
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