San Francisco, Other Cities: Protease Inhibitor Combination Trial

A critically important trial of the Merck protease inhibitor
(L-524) needs 60 volunteers who have never taken AZT or ddI
for more than two weeks, and who have a T-helper count of
under 500. The trial will take place in San Francisco and at
several other U.S. sites; we do not know the other cities at
press time. In San Francisco, the trial is planned to begin
in June.

Volunteers will be randomly assigned to receive three
different treatments: L-524 plus AZT plus ddI, L-524 alone,
and AZT plus ddI. (Merck has increased the dose of L-524 to
600 mg, from the 400 mg used in some earlier studies.) The
trial will last for 24 weeks; and if the therapy is well
tolerated and appears to have satisfactory antiviral effects,
patients who complete the 24 weeks will be offered continued
treatment through extensions of the study. The purpose is to
compare changes in HIV RNA and changes in T-helper count, and
to see if resistance to L-524 develops differently when that
drug is used alone or in combination.

The major entry criteria are:

* HIV positive, between 18 and 65 years of age;

* No AZT or ddI ever for over two weeks;

* T-helper count below 500 (there is no lower limit);

* Volunteers will be tested and must have HIV RNA levels of
at least 50,000 copies per milliliter (as determined by the
Roche Biomedical Laboratories quantitative PCR test);

* If on ddC, patients must be willing to discontinue at least
two weeks before the study treatment begins; if on d4T or
other investigational drugs, they must be willing to
discontinue 30 days before;

* No prior treatment with a protease inhibitor;

* No history of pancreatitis or peripheral neuropathy;

* Not positive for HBsAg (hepatitis B surface antigen,
indicating chronic active hepatitis B).

The ideal volunteer for this study would be someone with a
low T-helper count who has never had antiretroviral
treatment.

For more information about volunteering at the San Francisco
site, contact Christopher King, assistant director of
research, Conant Medical Group, through the trials
information line, 415/923-0555 (or by fax at 923-0337). Leave
your name, complete address, and phone number, and he will
call within five working days.

Comment

The reason this trial is important is that the Merck protease
inhibitor has shown good results temporarily, even in persons
with very low T-helper counts, in the very few cases tested
so far. But the drug stops working well, because HIV develops
resistance to it. In other diseases, such as tuberculosis or
cancer, combination therapy is used to overcome drug
resistance. The purpose of this trial is to make sure that
the combination of L-524 with AZT and ddI is safe, and to see
if it delays the development of resistance to the protease
inhibitor.

The reason for the exclusion of prior AZT and ddI is that if
these drugs have been used, virus resistant to them may have
already developed. In that case, the full benefit of the
combination would probably not be seen. It is important that
this trial get clean data, so that the future development of
L-524 (and other protease inhibitors) in combination
treatment can be planned correctly.