AIDS Treatment New, no. 183

about half (or a little more than half) that in the placebo
group.
This trial included 993 volunteers, who were randomly
assigned to take AZT or placebo for three years. All were
HIV positive and asymptomatic, with T-helper counts
above 400, when they started.
Why is this result different from that of the Concorde
study (the second major AZT trial, and the one which
accounted for much of the pessimism coming out of the
recent International Conference on AIDS in Berlin), which
found only a small and temporary benefit from AZT? No
one knows for sure, but a major difference is that the
patients entering the European-Australian study started at
an earlier stage in disease progression (median T-helper
count was about 650). Also, there were a number of other
differences between the trials, such as the exact definition
of what was counted as disease progression.
When the negative results of the Concorde AZT study
came out, most physicians did not change their prescribing
practices greatly; instead they chose to wait for more
information. Some of the press reports exaggerated the
pessimism, however, probably leading some patients to be
too quick to drop antiretroviral treatment. It is clear that
AZT, ddl, ddC, and probably d4T are poor anti-HIV drugs.
But for many patients, they seem to be clearly better than
nothing.
And the European-Australian study suggests that early
treatment is better than late. "The implication is that most
patients with HIV infection should be treated, but the
benefit may be greatest if therapy is begun when CD4 cell
counts are over 300 to 400 per cubic millimeter," according to an accompanying editorial.
[Cooper DA, Gatell JM, Kroon S, and others. Zidovudine in persons with asymptomatic HIV infection and
CD4+ cell counts greater than 400 per cubic millimeter.
The New England Journal of Medicine. July 29, 1993;
volume 329, number 5, pages 297-303. Also see editorial
on pages 351-352 of the same issue.]
Ateviridine: Upjohn "BHAP" Drug May
Be Useful After AZT Resistance
Ateviridine (U-87301E) is an experimental drug being
developed by Upjohn Laboratories. It is one of the "BHAP"
(bisheteroarylpiperzine) chemicals synthesized by that
company and tested for anti-HIV activity. Two BHAP
drugs, U-87301E and U-90152, are now in clinical trials.
(U-90152, sometimes called "super BHAP," is active in
lower concentrations. Due to the time required to analyze

results and get them published in journals, only U-87301E
is reported in the current article.)

The BHAP compounds are part of a class of drugs called
non-nucleoside reverse transcriptase (RT) inhibitors.
Unfortunately, a major problem with all the known drugs
which work this way is that HIV can quickly become
resistant to them. But different kinds of resistance (different mutations on the virus) develop with different nonnucleoside drugs; the different drugs of this class are not
interchangeable. This suggests that useful combination
treatments including these drugs may be possible. (Also,
low-level drug resistance can sometimes be overcome by
increasing the dose.)
The recent Ateviridine article reported that:
* Ateviridine was found to be effective against a number
of clinical isolates (HIV taken from patients), regardless of
whether or not the virus strains are AZT resistant or ddl
resistant. No virus tested was resistant to both ateviridine
and AZT, or to both ateviridine and ddl. The authors
suggested that such cross resistance might not occur.
(However, only a few different strains were tested and
reported in this paper.)
* Laboratory tests showed that the combination of
ateviridine and AZT might be useful against AZT-resistant viruses. This combination was synergistic against
AZT-resistant viruses (meaning that the combination
worked better than would be expected by adding how well
the drugs worked separately). But against AZT-susceptible virus, the combination was only additive. With ddl
the result was different; the combination was additive
whether or not the virus was resistant to ddl.
The authors conclude that ateviridine might be useful in
combination with AZT - especially in the common case
where patients have already been using AZT alone for
some time, and are likely to have developed strains of
AZT-resistant virus.
[Campbell TB, Young RK, Eron JJ, D' Aquila RT, Tarpley WG, and Kuritzkes DR. Inhibition of human immunodeficiency virus type 1 replication in vitro by the
bisheteroarylpiperzine ateviridine (U-87201E) in combination with zidovudine or didanosine. Journal of Infectious Diseases. August 1993; volume 168, pages 318 -326.]

AIDS Treatment News #183

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