Newsday - February 5, 1999
Laurie Garrett - Staff Correspondent

For example, patients recover immunity to some deadly opportunistic infections but appear unable to fight diseases for which they were vaccinated as children or to target HIV itself.

Yesterday, scientists reported that use of Highly Active Antiretroviral Therapy, or HAART, can in at least half of all HIV patients push the viral population down to undetectable levels, allowing the beleaguered immune system to reconstruct itself. But it appears the reconstructed system bears little resemblance to the immune system of a healthy individual, and it's unclear exactly how well the cells and antibodies in the system can protect HAART patients.

At the Conference on Retroviruses and Opportunistic Infections here, Dr. Brigitte Autran of the Hopital Pitie Salpetriere in Paris presented evidence on patients with advanced HIV infection. She said that after two to three years on HAART, these patients can muster reasonable numbers of immune-system cells that can recognize and destroy some pathogens. In particular, she said, cytomegalovirus, the primary cause of blindness in HIV disease, can be controlled by the immune systems of HAART patients.

"The major indication clinically of a restored immune system is the dramatic decline in opportunistic infections that we all have seen," Dr. Constance Benson of the University of Colorado Health Science Center in Denver said. She noted that all of the most common secondary infection seen before 1996 in HIV patients have virtually disappeared in the HAART era.

And Dr. Jose Lopez and his colleagues from 21 Spanish hospitals proved the point by stopping preventive medication for parasitic pneumonia in HAART patients. Once the No.1 killer of people with AIDS, pneumocystis pneumonia is now so well-controlled, preventative medicine is unnecessary, he said.

That's the good news. But, Autran said, patients were not able to control infections for which they were vaccinated during their childhoods, such as tetanus. Further, Autran's HAART patients could not muster immune responses against HIV itself.

Taken together, these observations indicate HAART patients can only raise successful immune responses against pathogens they see regularly. Cytomegalovirus is a ubiquitous organism found in everybody's blood, so the immune systems of HAART patients see the pathogen constantly and generate cells and antibodies that attack it. But tetanus is something people rarely encounter, so HAART patients, unlike their HIV-negative counterparts, fail to raise immune responses against it.

And the ultimate irony is that HAART, when successful, kills all but a few million HIVs that are forced into hiding. Therefore, the immune system doesn't see HIV anymore and stops making cells and antibodies against the virus.

Reasoning that it might be a good idea to let the immune systems of HAART patients see HIV, Dr. Franco Lori and his colleagues at the Research Institute for Genetic and Human Therapy in Washington, D.C., stopped treatment in three patients. The idea was to treat the individuals for 18 months, assuring that their viral loads had reached undetectable levels, and then stop HAART for two weeks. HIV then surged into the patients' bodies, triggering cellular immune responses. If the viral loads weren't controlled immediately, Lori resumed therapy, then repeated the process a few weeks later. Two of the three patients appear to be controlling HIV, keeping the virus down to undetectable levels, 100 days after HAART treatment ceased, Lori said.

"What's very important . . . is no data suggests that this is something people should be doing" as a matter of routine clinical practice, said Dr. Bruce Walker of Harvard Medical School, whose group has tried a similar approach.

Part of the problem may be that HIV is very good at hiding from the immune system, a feat it accomplishes by living inside T-cells of the immune system itself. And even when HAART appears to be perfectly successful, Dr. Z.Q. Zhang of the Aaron Diamond AIDS Research Center in Manhattan said yesterday, the virus quietly, secretly replicates and mutates.

The best guess, at this point, is that HIV blocks production of T-cells from the thymus. And when patients go on HAART, the viral population is lowered just far enough to permit renewed thymus production of the vital immune system cells, Dr. Richard Koup of the University of Texas Southwestern Medical Center in Dallas said.

But the T-cells that suddenly are manufactured appear to be heavily skewed. They attack the sorts of pathogens that cause opportunistic infections but do not target HIV. And they may not target such serious pathogens as influenza, malaria or measles.
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