VIRUSMYTH HOMEPAGE


NIGHTMARE ON AZT STREET

By Neenyah Ostrom

New York Native 4 Sept. 1995


Zidovudine, or AZT, has had a rough year. Recent studies that have shown the drug to be ineffective at best and, in some instances, actually harmful. The worst news for AZT and its manufacturer Burroughs Wellcome, however, is probably yet to come, when the birth defects found in babies born to women treated with AZT while pregnant become common knowledge among patients, clinicians, and researchers-and the press.

The US government has recently begun a new campaign urging all pregnant women to be tested for HIV antibodies and, if testing positive, to take AZT to stop transmission of the virus to their fetuses.

Federal health officials insist that there is no threat of deformed babies being born to women who take AZT during pregnancy. In a published report of the Centers for Disease Control study of AZT in pregnant women (ACTG 076), it wasn't revealed what types of birth defects occurred; they were simply described as minor."

In contrast, a study performed in Asia reports some shocking deformities in babies born to women who took AZT while pregnant.

The Asian study was published a full year ago.

Why are government scientists continuing to insist that AZT is a safe drug to give to pregnant women?

This is especially perplexing in light of recent studies performed on non-pregnant subjects that have shown the drug to be ineffectual, in addition to being extremely toxic.

AZT has been found to be almost completely useless in "early intervention" studies published both in the US and Europe; AZT has been found to so impair an individual's quality of life that its side effects have been judged to cancel out any perceived benefit; AZT has been pronounced to be downright harmful when taken by children. In fact, HIV-positive children who take AZT die faster than children who don't.

Nevertheless, in July 1994, the US Public Health Service recommended that all HIV-positive pregnant women be given AZT to stop transmission of the virus to their fetuses. This recommendation was made on the basis of one truncated study; no long-term follow-up documenting the health and development of the babies born to the women treated while pregnant has been done.

In July 1995, the Centers for Disease Control-one part of the Public Health Service-went even further and recommended that every pregnant woman in the country be tested for HIV, so she could be given AZT if she tested positive for HIV antibodies.

CDC scientists insist that their study of AZT in pregnant women noted only the "normal" rate of birth defects, i.e. no more than two to three percent of babies were born with deformities.

A study performed in Asia, however, found that birth defects occurred at up to five times this "normal" frequency.

The "minor" birth defects noted in the CDC-sponsored, prematurely ended, study were also observed in the Asian study. An example of such a minor defect is a child born with extra fingers when there is no family history of polydactyly, or extra digits (which is generally a genetic condition; since AZT interferes with DNA synthesis, it is not an unexpected "minor" abnormality).

However, the Asian study documented very serious birth defects in the children born to women who took AZT while pregnant: holes in the chest, abnormally small brains, lowered ears, neurological abnormalities, and heart defects, among others.

In a full 25 percent of the 104 women followed in the Asian study, the child either died (from spontaneous or induced abortion, due to abnormalities), or was born with a birth defect.

According to the CDC"s statistics, the incidence of babies born with any type of birth defect is about two percent. In the AZT-treated women in the Asian study, ten percent of the babies who survived had birth defects.

*****

I first learned in 1992 that babies born to women given AZT while pregnant had various types of deformities. In the June 1992 ACT UP Update there was a report on early finding s from the federal study of AZT in pregnant women, ACTG 076: "ACTG 076 (giving AZT to pregnant women to assess its ability to interrupt transmission of HIV to a fetus) is enrolling so slowly that it may take ten years to complete this trial by which time AZT will be anachronistic (if it isn't already)," the ACT UP publication noted. "We had to pressure for data from the first 30 women and still only have an oral report. This showed that 10 percent of the children had extra digits (fingers, toes), something which Burroughs Wellcome had found in their informal pregnancy data; five babies were born with neutropenia [a blood cell abnormality] but apparently it reversed itself."

When I tried to track down more evidence about this incidence of birth defects, the unexpected happened: A government spokesperson would not deny the report.

I had first attempted to elicit further information from Burroughs Wellcome, since the company was mentioned in the ACT UP Update as having released data to that group. Company spokesperson Kathy Bartlett refused to comment for the story I wrote in the July 13, 1992, New York Native; Burroughs Wellcome, I was told, had only supplied the drug for the study. ACTG 076 was actually performed under the auspices of the National Institute of Allergy and Infectious Diseases (NIAID), as are almost all anti-"AIDS" drug trials.

On July 1, 1992, I called Marion Glick in NIAID's Office of Communications. Glick said she would have to consult her superiors.

"When Glick telephoned the Native later the same day, she declined to confirm or deny the report. S he said she had been instructed to direct such inquiries to the two co-directors of trial ACTG 076, Dr. Edward Connor (at the University of Medicine and Dentistry of New Jersey) and Dr. Rhoda Sperling (at Mt. Sinai Hospital in New York City)," I reported. Neither Connor nor Sperling was available for comment.

For the next two years, I tried to obtain, under the Freedom of Information Act, federal government data on the incidence of birth defects in children born to mothers given AZT while pregnant. My repeated re-quests were denied. A final appeal was sent to Assistant Secretary for Health Dr. Philip R. Lee, who rules on continuing battles over access to federal health records.

Lee upheld the National Institute of Health's denial of my repeated requests.

He told me how I could obtain the data, however: I could sue the federal government.

"Because this denial constitutes final agency action, you may seek review in the District Court of the United States in the district in which you reside, in which your principal place of business is located, in which the records are located, or in the District of Columbia," Lee wrote me on January 6, 1994.

Shortly thereafter, ACTG 076-like every other US government-sponsored AZT trial-was prematurely ended, with no plans for long-term follow-up of the effects of AZT on these infants, and no release of data concerning the incidence or type of birth defects seen in the surviving infants.

Although it only recently came to my attention, the Asian study reporting such birth defects as heart defects in babies treated in utero with AZT was published in July 1994.

The following month, the US government issued its recommendation that all HIV-positive pregnant women take AZT.

*****

When the CDC published its results from ACTG 076 in The New England Journal of Medicine in November 1994, this is what was reported about "structural abnormalities" in the infants:

The incidence of minor and major abnormalities was similar in the two groups [babies born to women who received AZT and those who received a placebo]. Congenital cardiac anomalies were confirmed in ten infants (five in each group). Congenital abnormalities of the central nervous system were reported in five infants (three in the zidovudine group and two in the placebo group). Eighteen other major anomalies were reported, nine in each group. No specific minor or major abnormalities were clustered in either group. (1)

Aside from the oddity of precisely the same number of reported abnormalities occurring in both placebo- and AZT-treated infants-five cardiac abnormalities in each group; nine "major anomalies"-the deformities observed were not listed or described.

Eighteen "major anomalies" were reported among these babies-but the CDC report doesn't say what they were. Were these children missing limbs? Did they suffer from anencephaly, the lack of a brain? Did they have congenital heart abnormalities, too-small brains, club feet, or what?

The CDC continues to refuse to put that information on the record.

Fortunately, scientists outside the United States have been more forthcoming.

*****

The study describing some of the birth defects of children born to pregnant women given AZT was published by two scientists from the United Arab Emirates University, Rachana M. Kumar and Phillip F. Hughes, and Ashhok Khurranna from the Sanjay Ghandi Memorial Hospital in Uttar Pradesh, India. (2)

While they noted that their study lent "tenuous support" to the use of AZT during pregnancy, Kumar and colleagues described the birth defects observed in the babies in detail.

They observed 104 pregnant, Indian women given AZT between February 1990 and March 1993.

Four outcomes of the pregnancy and AZT treatment were recorded: (a) birth defects; (b) lack of birth defects; (c) spontaneous fetal death; (d) induced abortion.

If a child weighed less than 2,500 grams at birth, any birth defects were ignored in the computation of the data.

Eight spontaneous and eight induced abortions occurred among the 104 women.

Eight babies were born who weighed more than 2,500 grams and had birth defects. They included:

1. Two male infants with the "minor abnormalities" of "low-set ears, retrognathia [a mis-aligned jaw], prominent epicanthal folds [i.e., unexpected skin flaps above the eye, which can be a sign of mental retardation], hirsutism [abnormal hairiness], triangular facies with blue sclera [a triangular-shaped face with abnormally blue eyes], hyperpigmented skin macules, and prominent sacral dimple [a pronounced indentation at the bottom of the spinal cord]."

2. A female infant was born with extra fingers on both hands (the report doesn't say how many "extra digits" grew on each hand). "There was no similar family history," Kumar and co-workers noted.

3. One child was diagnosed as having "fetal alcohol syndrome," although there was no evidence that the mother consumed alcohol.

4. A male infant was born with a serious congenital heart defect ("asymptomatic atrial septal defect") and "pectus excavaatum," a depression or actual hole in the chest. This child died at the age of five months.

5. A male infant was born with an abnormally small brain (microencephaly) and chorioretinitis (a condition that rapidly results in blindness, due to lesions on the retina).

6. Another male infant was born with the same type of hole in his chest as the previously described child ("pectus excavatum").

7. A female was born with albinism (no pigmentation) and congenital ptosis, a condition in which the upper eyelid droops uncontrollably (which interferes with eyesight) because of nerve damage.

Kumar and colleagues are very cautious in the conclusions they draw from their study. They note that "the majority" of babies born to HIV-positive women will not develop "AIDS." Therefore, they further note, the risks of administering AZT should be weighed against the likelihood of the child developing "AIDS."

"Put simply, from a fetal viewpoint the risk of intervention needs to be less than the risk of vertical transmission," Kumar and co-workers argue. They note rather glumly, moreover, that "Use of zidovudine in this population will probably increase, even without sufficient data concerning the safety or efficacy of this drug during pregnancy."

These researchers also address the major problem facing clinicians: There has been no study performed that adequately evaluates AZT's possible teratogenic effects-that is, the drug's potential to cause birth defects and deformities in children exposed in the womb.

"Teratogenic potential of Zidovudine in humans is still unknown," Kumar and colleagues point out. "While animal studies have shown a direct toxic effect on mouse embryos, high-dose administration to pregnant rats and rabbits reportedly failed to demonstrate any fetal effects. However, the potential for cross-species differences tragically exemplified by thalidomide cannot be forgotten. . . ." *

References

(1) Connor, Edward M., Rhoda S. Sperling, et al.; "Reduction of Maternal-Infant Transmission of Human Immunodeficiency Virus Type Infant Transmission of Human Immunodeficiency Virus Type 1 With Zidovudine Treatment"; The New England Journal of Medicine 331(18):1173, November 3, 1994.

(2) Kumar, Rachana M., Phillip F. Hughes, and Ashok Khurranna; "Zidovudine Use in Pregnancy: A Report on 104 Cases and the Occurrence of Birth Defects"; Journal of the Acquired Immune Deficiency Syndromes 7:1034, July 1994.


VIRUSMYTH HOMEPAGE