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1999: Basic AIDS Issues

By John S. James
Publisher, AIDS Treatment News

aids1999.gif - 8.62 K This year more than most, it is unclear where AIDS research is heading. There may be a better sense of direction after the Retroviruses conference (6th Conference on Retroviruses and Opportunistic Infections, Chicago, January 31 - February 4).

Politics and treatment access issues are also unpredictable this year.

From what we do know today, here are some of the areas we will be following most closely in 1999:
The antiviral T-20 (see AIDS Treatment News #293, April 17, 1998; #300, August 7, 1998; and #306, November 6, 1998). This potential treatment, which for the foreseeable future must be given by injection, is known to be highly active against HIV-1 in people.

And because it uses a completely different mechanism of action from any treatment now in use, it is likely to open a new approach to therapy, and have no cross-resistance with existing drugs--especially important for those who have already had extensive HIV treatment. Still unknown: how rapidly will resistance to T-20 develop in practice?

Research on other new classes of drugs, some based on recently discovered potential targets (such as the specific mechanisms of viral entry involving co-receptors).

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Although basic research has proceeded rapidly, it is likely to take some time before new treatments using these approaches are ready for human testing. (T-20 is essentially one such drug which happened to be discovered early.)

Research on how the body loses its natural ability to control HIV (except in long-term nonprogressors, who may be able to control HIV indefinitely without treatment). When HIV infection first occurs, the virus reaches very high levels, often causing symptoms of a severe flu-like illness.

Then the body's immune response greatly reduces the level of the virus; the immune system itself, at first, does much better at suppressing HIV than any known drug. But later, usually over a number of years, the body gradually loses this ability to keep the virus in check, and the resulting high levels of HIV cause more immune damage, leading to symptomatic disease and AIDS.

A new measurement technique to study the natural production and lifespan of immune cells in the body. Newly created CD4 cells can be marked with deuterium, a harmless non-radioactive isotope of hydrogen, which can be detected with special equipment.

A major paper published this week in Nature Medicine used this method to show that HIV interferes with the production of CD4 T-cells--challenging the prevailing model of greatly increased production and rapid killing of these cells. If confirmed, this finding could lead to new kinds of treatment focused on maintaining normal production of immune cells.

HIV-specific CD4 helper response.
When HIV is well suppressed by antiretroviral drugs, immune responses to various opportunistic pathogens usually return, more or less rapidly in different patients.

But the ability of CD4 helper T-cells to recognize HIV is lost very rapidly (except in long-term nonprogressors), and even when the virus is suppressed, that ability returns very slowly or not at all.

Some early results suggest that it may be possible to restore this response by immunization (see AIDS Treatment News #298, July 10, 1998); there may also be other immune-based strategies which could work. At this time, however, there is no proof that restoring this response will result in clinical benefit.

aidsfat.jpg - 17.27 KBody-shape changes and abnormal fat metabolism associated with HIV treatments, especially protease inhibitors.
Here the most important research, we believe, will be (1) to find the mechanisms of action, so that treatments can be rationally designed, and (2) meanwhile to find and study empirical treatments (ones which seem to help, although no one knows exactly how).

Laboratory tests of viral resistance to drugs.
These tests (both phenotype and genotype) will become increasingly important in medical care, but are likely to be valuable only in specific situations.

For example, when a combination treatment is failing to control the virus, a resistance test may help decide what new combination to change to; in this case, the test must be done while the patient is still taking the drugs which are failing (since without the drugs, the resistant virus is likely to be replaced by the original non-resistant virus, and decline to very low levels which the tests will not detect--yet be ready to come back almost immediately if the drug is resumed).

Another potential use is for people who are likely to have been infected by a resistant virus (for example, if they were infected in San Francisco or other cities where many people have been treated extensively); in this case the test can be done before treatment is started, to avoid drugs which are unlikely to be effective.

New tests to see if opportunistic infection prophylaxis is still necessary.
Researchers are developing tests which may be able to tell if a patient's immune system is responding well enough to specific opportunistic pathogens that prophylaxis for them is no longer necessary.

Today, this decision is often made on the basis of CD4 count recovery after successful antiretroviral therapy; the new tests, when they are available, should allow more accurate determination.

potleaf.gif - 4.72 KAlternative/complementary treatments.
Many treatments are not developed by the pharmaceutical mainstream because of lack of commercial incentive, even when there is reason to believe they may have value (an example is DHEA).

Nutrition, exercise, stress reduction, and other lifestyle improvements are also under-researched, for similar reasons. Usually such potential treatments are far less dangerous and far less expensive than high-tech, patented pharmaceuticals.

They deserve attention for several reasons: to possibly complement mainstream treatments in helping reduce disease progression; to improve quality of life, for example by helping to control certain side effects of drugs; and for developing countries, where they may be the only treatments affordable for most people.

Treatment access issues include:

--Serious problems with reimbursement for HIV care by many managed-care organizations--which cut their costs by refusing to recognize HIV care as a specialty, and pay only the healthy-adult capitated rate for taking care of patients with HIV disease or AIDS.

  • Medicaid and ADAP funding, and rules on working while disabled.

  • Lack of trials of salvage therapies.

  • Drug pricing.

  • International access to treatment, especially use of compulsory-licensing rules to enable the use of certain critical drugs in countries where people would otherwise do without.

  • Inferior treatment for the U.S. homeless and marginally housed, even when they can adhere well to the antiretroviral regimen.

  • Needle-exchange, both to prevent new infection and to bring drug users already infected into medical care.

  • Inadequate pain relief when needed in serious illness.

  • Legal access to medical marijuana.

  • Freedom of information, including potential excesses in copyright legislation, Internet sexual censorship, and embargoes of taxpayer-funded research results by medical journals and conferences.
    AIDS Treatment News
    Published twice monthly

    Subscription and Editorial Office:

    P.O. Box 411256
    San Francisco, CA 94141
    800/TREAT-1-2 toll-free U.S. and Canada
    415/255-0588 regular office number
    Fax: 415/255-4659

    Editor and Publisher: John S. James
    Associate Editor: Tadd T. Tobias
    Reader Services: Tom Fontaine and Denny Smith
    Operations Manager: Danalan Richard Copeland

    Statement of Purpose:
    AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. We interview physicians, scientists, other health professionals, and persons with AIDS or HIV; we also collect information from meetings and conferences, medical journals, and computer databases. Long-term survivors have usually tried many different treatments, and found combinations which work for them. AIDS Treatment News does not recommend particular therapies, but seeks to increase the options available.

    ISSN # 1052-4207
    Copyright 1998 by John S. James.

  • © 1997-99 BEI