Mycoplasma: CRI Plans Doxycycline Treatment Study

New York's Community Research Initiative (CRI), one of the

pioneers of community-based AIDS research, is developing a trial

to see whether the antibiotic doxycycline can help certain

patients with an ARC diagnosis -- and whether a blood test for

mycoplasma infection can predict who might benefit. This trial

will test the hypothesis of Luc Montagnier, M. D. -- one of the

discoverers of the AIDS virus -- that mycoplasma infection might

be an important cofactor in the development of AIDS.



Background



Mycoplasmas are organisms between viruses and bacteria in

complexity. They are known to cause some human diseases, and

they can be controlled with certain antibiotics. During the last

several years, Shyh-Ching Lo, M. D., and other researchers at the

U. S. Armed Forces Institute of Pathology found a mycoplasma

which appeared to be a previously unknown species in organs of 22

of 34 persons who had died of AIDS, and reported evidence that

this mycoplasma may be causing organ failures. (For more

information on this work, see AIDS TREATMENT NEWS #95, January

19, 1990.) In laboratory tests, the antibiotics most active

against this mycoplasma appear to be doxycycline and

ciprofloxicin (see Lo, SC and others, Sixth International

Conference, abstract #Th.B. 536).



At a special meeting organized at the Sixth International

Conference on AIDS last month in San Francisco, Dr. Montagnier

reported laboratory studies supporting a hypothesis that

mycoplasma might be a major cofactor in the development of AIDS

-- not just an opportunistic infection. His team found

mycoplasma in the blood of about one third of AIDS patients; the

organisms are hard to detect, so they may be present in others,

too.



Also, the researchers found that antibiotics which inhibited

the mycoplasma prevented HIV from killing cells in the

laboratory, although the drugs did not affect HIV directly. Dr.

Montagnier speculated that HIV might become more destructive

later in the disease than early after infection, because of later

mycoplasma infection. An abstract by Dr. Montagnier and others

(#1072, accepted for publication-only at the Conference, without

a talk or a poster presentation) reported that doxycycline

protected cells against destruction by HIV, even though the virus

continued to multiply within the already-infected cells. HIV

cultures treated with tetracycline lost their ability to kill

cells even after the tetracycline was removed, suggesting that a

tetracycline-susceptible contaminant in the culture (probably a

mycoplasma) enabled the HIV to kill the cells.



Dr. Montagnier has given high priority to further

investigation of the possible role of mycoplasma in AIDS, and has

assigned 15 people, half of his unit, to work on it.



For more information on this research, see the interview

with Dr. Montagnier by Martin Delaney of Project Inform,

published in The Advocate, July 3, 1990.







The CRI Study

The treatment study now being planned by the Community

Research Initiative will randomize 150 patients with an ARC

diagnosis to one of three daily doses of doxycycline: 50, 100,

or 200 mg twice a day. Researchers will monitor patients'

clinical status and do the usual blood work; in addition, a

special laboratory will test blood samples for mycoplasma, at

baseline and at three-month intervals. Because clinical

evaluations can be subjective, the mycoplasma test results will

be blinded; a Data Safety Monitoring Board will examine the

unblinded data after six months, in order to halt the study if

the results are dramatic enough to justify that step.



The CRI has raised about half of the $300,000 required for

this study; it wants to have at least two thirds of the funding

before beginning, to assure that the trial can be completed.

Doxycycline is a generic drug, as its patent has expired;

therefore pharmaceutical companies have no incentive to fund

research. Federal agencies are not yet ready to conduct a

treatment trial for mycoplasma, although they may do a prevalence

study by analyzing blood and tissue samples.



This CRI study is important for several reasons:



* Even before mycoplasma became an issue, some physicians

have prescribed doxycycline empirically for people with HIV who

had unknown illnesses. The rationale is that many people with

AIDS have opportunistic infections which have not been diagnosed

(as has been shown by autopsy studies); doxycycline is fairly

safe, and effective against many disease-causing organisms, so it

could be worth trying when attempts to diagnose a problem have

failed. The doxycycline trial will provide the best available

data to guide empirical use of the antibiotic by persons with HIV

-- whether or not mycoplasma is important.



* The study will test Dr. Montagnier's hypothesis that

mycoplasma infection may be a major cofactor in AIDS. It will

show whether the available mycoplasma blood test is helpful in

guiding the use of doxycycline, and whether testing for

mycoplasma has prognostic value.



* Doxycycline is readily available, very well known in human

use, and inexpensive. Therefore if the study does find a

positive result, it could have rapid impact on AIDS treatment in

the United States and elsewhere.



If you can help in the fundraising or otherwise in the

development of this study, call Bernard Bihari, M. D., Executive

Director, Community Research Initiative, 212/481-1050.