Subject: U. S. Officials, European Researchers Clash Over Early Treatment With AZT 
Date: Published: 4/2/93 (92 lines)
Source: Wall Street Journal. Copyright Dow Jones & Co. Inc.

    Technology & Medicine:
    U. S. Officials, European Researchers
    Clash Over Early Treatment With AZT
    ----
    By Marilyn Chase
    Staff Reporter of The Wall Street Journal

    A trans-Atlantic debate has erupted over using Wellcome PLC's
 drug AZT to treat asymptomatic patients infected with the AIDS
 virus.
    The controversy pits an Anglo-French research group against U. S. 
 health officials who have advocated such treatment.
    The study, called the Concorde Trial, concludes early AZT
 treatment fails to prolong three-year survival rates.  The study
 examined 1,750 symptom-free people infected with human
 immunodeficiency virus, which causes AIDS.  Half received AZT, and
 half got a placebo or dummy drug until the onset of symptoms, when
 they switched to AZT.  After three years, the survival rate was 92%
 in the early treatment group and 93% in the deferred treatment
 group.
    "There was no significant difference in clinical outcome between
 the two therapeutic strategies," said Concorde researchers
 Jean-Pierre Aboulker of Villejuif, France, and Ann Marie Swart of
 London, previewing their work in a letter to the British journal
 Lancet this week.
    Similarly, Drs. Aboulker and Swart found "no significant
 difference" in the patients' progression to full-blown AIDS.  
 However, the study did show that patients treated early maintained
 higher levels of disease-fighting white blood cells of the immune
 system, known as CD4 cells.  Their failure to link this sign with
 better survival "casts doubt on the value" of CD4 cells in judging
 antiviral drugs, they asserted.
    In Rockville, Md., the U. S. Food and Drug Administration -- which
 has blessed the notion of early care when CD4 counts fall below 500,
 or about half the normal level -- reacted quickly.
    "No one has ever seen AZT as a home run," said FDA Commissioner
 David Kessler in a telephone interview.  "It is, at best, a solid
 single.  But when you're four runs behind in the ninth inning, you
 take a single."  Further, he upheld monitoring of CD4 cell levels as
 a window on immune health.
    U. S. officials jumped on the Concorde claims.  Certain AIDS
 activists have argued, despite studies to the contrary, that AZT's
 benefits aren't worth the toxicity, mainly bone marrow suppression.
 U. S. officials cautioned against abandoning the drug, while noting
 AZT's flaws are "no surprise" to anyone following treatment trends.
    FDA has acknowledged the long-accepted view that AZT's benefits
 may subside after 12 to 18 months as the virus mutates to evade the
 drug's effects.  However, "this study does not call into question the
 clinical importance of AZT in treating symptomatic HIV disease," the
 FDA stressed in a position paper.
    The office of Anthony S. Fauci, director of the National
 Institute of Allergy and Infectious Diseases, issued a statement
 from an HIV conference in Albuquerque, N. M., urging patients to take
 the report in context.  Wellcome PLC in London and its U. S. unit in
 North Carolina both issued statements challenging the Concorde's
 study methodology.
    What isn't clear is how much impact the Concorde study will have
 on the AIDS treatment in the U. S., where AZT's role as a solo
 treatment has already been markedly eroded as patients embrace newer
 antivirals or combination treatments.  Indeed, many U. S. doctors now
 accept the view -- propounded by a NIAID study a year ago -- that
 patients benefit by switching to a second drug, Bristol-Myers Squibb
 Co. 's DDI, after just four months on AZT.  A third antiviral drug,
 Hoffman-La Roche's DDC, is used in combinations with, or as an
 alternative to, AZT.  
    "No patient or doctor should change their use of AZT" based on
 the Concorde study, urged Daniel Hoth, director of NIAID's Division
 of AIDS.  Further, he suggested the Concorde's study design is
 outdated, because AZT as a solo drug isn't the ideal of AIDS care.
 "Today's world is different; we have more treatment options," he
 said.  NIAID has called for a state-of-the-art conference this
 summer.
    Concorde's three-year observations overshadow three earlier U. S. 
 studies suggesting early treatment can delay the onset of AIDS or
 AIDS-related complex in the short term.  But it confirms findings of
 a fourth study from the Veterans Affairs department showing scant
 effects on long-term survival.
    "We know resistance develops in people after about a year," said
 David Feigal, director of FDA's division of antiviral drug products.
 "They're choosing to present the bottom line -- what happened after
 three years.  We need to see more data to know if there were early
 effects -- at one year, 18 months, and two years -- showing
 differences in progression."

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