Recent Journal Articles

do not focus on articles published elsewhere, but prefer in-
depth reports which may come out months before the journal
articles (or months after, giving us a chance to hear
professional reaction). We have left reporting of recent
articles to others. However, the most comprehensive sources
on recent journals are either very expensive (AIDS WEEKLY) or
often very technical (ATIN: AIDS TARGETED INFORMATION).

Our coverage will not be comprehensive. For every article
included below, we examined about ten other recent AIDS
treatment articles which we chose not to include -- mostly
because we thought they would not be relevant to our readers.
Some of those we omitted are important for physicians, but
concern specialized areas which we could not cover
adequately.

Note that we cannot do the same in-depth investigation for
these reports as we do for major articles. The main focus
here is the fact that the article appeared. But sometimes we
will include background to help readers understand the
context.

We plan to focus on information which is practical now, and
also on information which helps readers understand
developments which may be important for the future. But there
are thousands of different medical journals, and we can only
scan a few. We will inevitably miss important articles, and
hope that readers will bring them to our attention.


** AZT: European-Australian Study Shows Benefit, Especially
in Early Treatment

The third large trial of AZT, by the European-Australian
Collaborative Group, was published in the July 29 New England
Journal of Medicine. The results are not new, having been
presented in conferences and known to physicians for some
time, but the fully peer reviewed publication provides an
opportunity for a closer look. And no matter how you look at
the data, AZT showed some benefit on the average, with
disease progression in the AZT group 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, ddI, 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 non-nucleoside 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 ddI
resistant. No virus tested was resistant to both ateviridine
and AZT, or to both ateviridine and ddI. 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 ddI the result was different; the combination
was additive whether or not the virus was resistant to ddI.

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.]


** TMP-SMX: High Treatment Dose Can Cause Hyperkalemia

A study by physicians at the Brookdale Hospital Medical
Center in Brooklyn, New York, measured serum potassium levels
in 25 patients who were given high-dose TMP-SMX for treatment
of pneumocystis, compared with 26 patients not given that
drug. They concluded that high-dose TMP-SMX could result in
life-threatening hyperkalemia, particularly 7 to 10 days
after the start of treatment, and that serum potassium levels
should be monitored closely. (Note: this study looked at the
high doses used to treat pneumocystis -- not the much lower
doses used for prophylaxis.)

[Greenberg S, Reiser IW, Chou SY, and Porush JG.
Trimethoprim-sulfamethoxazole induces reversible
hyperkalemia. ANNALS OF INTERNAL MEDICINE. August 15, 1993;
volume 119, number 4, pages 291-295. The following article
starting on page 296, by different authors, looks at a
possible cause, involving effects of the drug on the kidney.]


** Lymphoma: EBV Test May Help in Diagnosis

A research test (not now available commercially) found
Epstein-Barr virus DNA in the cerebrospinal fluid from 17 of
17 patients who were diagnosed at autopsy with primary CNS
lymphoma -- but in only 1 of 68 HIV-positive patients without
detectable lymphoma at autopsy. The authors concluded that
the test was 100 percent sensitive and 98.5 percent specific
for AIDS-associated primary CNS lymphoma.

[Cinque P, Brytting M, Vago L, Castagna A, Parravicini C, and
Zanchetta N. Epstein-Barr virus DNA in cerebrospinal fluid
from patients with AIDS-related primary lymphoma of the
central nervous system. THE LANCET. August 14, 1993; volume
342, pages 398-401.]