Frerichs, R.R. Response to AZT/MTC underscores women's health.

SEA-AIDS Network, April 6, 1998.

Posted in response to:

SEA-AIDS, April 5, 1998

From Joe Thomas, Hong Kong

This is to express my concerns in promoting AZT monotherapy among pregnant women in developing countries as it underscore women's health.

Based on the findings of a recent study in Thailand, short courses of AZT may decrease prenatal transmission many international agencies are currently advocating the use of AZT based mono therapy for pregnant women living with HIV in developing countries, to reduce the chance of vertical HIV transmission. It appears that promoting AZT mono therapy among pregnant women underscore women's health and such a policy need wider discussion and through scrutiny before promoted in developing countries.

The Glaxo Wellcome (who has the monopoly of AZT) has recently announced their intention to reduce the price of AZT. However, promoting AZT should not be based only on the marketing strategy of one single company. Which is akin to an unethical product endorsement. It appears that the commercial interest of Glaxo Wellcome has got prominence over the health care needs of pregnant women in developing countries.

Some of the key issues which needs further discussions are:

1. The recommendations, which many healthcare workers particularly in developing countries has misinterpreted as ruling against combination therapy during pregnancy.

2. Almost, there is a global consensus on the ineffectiveness of AZT monotherapy as on a long term it may contribute to resistance.

3. Promoting the use of AZT mono therapy among the pregnant women under the guise of reducing the Perinatal transmission underscore the health care needs of the mother.

4. The Thai study, was not reported in a peer reviewed journal or in any scientific meetings so that the data and the results could have been peer reviewed. Which was the common practice adopted in other latest findings on the effectiveness of many other Highly Active Anti Retroviral Therapies. The investigators of the study did not sufficiently justify the reasons to deviate from the established practice in reporting the results of Thai study.

5. The treatment group was consist of 198 AZT recipients and 199 placebo recipients. In the placebo group 35 children where born with HIV and only 17 children were born with HIV among the AZT recipient group. Please, don't fail to take note of the lower transmission rate of the group which did not receive any treatment.

6. Impact of physiological categories such as the duration of labor, procedures and nature of clinical assistance received during the labor (14% had cesarean deliveries), the viral load at the enrolment, previous treatment histories, duration of infection were not taken into consideration when the result was presented ( it is not available to the readers if they have considered those issues).

7. At the enrollment the median age of the clinical trial participants was 24 years. What is the significance of age on vertical transmission ?  There was no data on co-morbidity or the progression rate of infection among the treatment group. What would have been the impact of co-morbidity on the rate of transmission?

These are some of the serious limitations of this study. Without taking into consideration of such limitations and promoting AZT mono therapy among pregnant women in developing countries is not justifiable as it underscore the health care needs of women with HIV/AIDS in developing countries.

[References of the brief note is available to those who are keen to engage in a dialogue on this issue].

Dr. Joe Thomas

Community Research Program on AIDS,

The Chinese University of Hong Kong

B,7/B. Prince of Wales Hospital

Shatin, N.T., HONG KONG.

R.R. Frerichs Posting

When facing public health problems, there are often many reasons people do not call for action. First, the intervention or prevention activity may be too costly for governments to consider without raising taxes or other revenues. Second, public safety needs may conflict with individual rights to freedom of action. Third, problems of day-to-day living may be so great that policy issues are left for others to address. All of these factors have been evident in not addressing HIV/AIDS. Whatever the instance or the reason, the result all too often is no epidemiologically meaningful action.

The correspondence of Dr. Joe Thomas concerning AZT administration during pregnancy (received 4/5/98), should be very welcome by those who favor inaction. He questions the findings and conclusions of a recent study in Thailand of low-dose AZT during pregnancy (showing proper scientific skepticism), but provides little guidance for those attempting to save lives of young children who otherwise would be born infected with HIV (showing no pragmatism). Within this context, I would like to briefly address some of the issues raised by Dr. Thomas. 

I personally know Dr. Thomas and remain impressed with his dedication to his native India, general concern for public health and his commitment to dealing with the HIV epidemic in Asia. Thus my comments are not focused on him per se, but rather at the points he raised in his recent correspondence. My main concern is that his posting may be used to justify public health inaction.

1. The study in question was conducted by scientists in Thailand and the United States working through the HIV/AIDS Collaboration in Thailand and the Centers for Disease Control and Prevention (CDC) in the United States. I believe that CDC funded most of the investigation.

2. Because of the worldwide interest in this topic, the investigators likely wanted to publish their findings quickly. The first news of the study in a medical publication occurred in The Lancet on February 28, 1998. The scientific report appeared one week later (March 6, 1998) in the Morbidity and Mortality Weekly Report (MMWR) published by CDC. I imagine that full documentation in a peer reviewed international journal may not appear for another 8-12 months, because of the need of the Thai/US investigators to wrap up all aspects of the study and the long time it usually takes from submission to publication.

Those interested in the MMWR published study can obtain the text by going to the internet address (no longer available). They will find that the study was able to follow two groups of pregnant women, one with 195 who received zidovudine (more widely known as AZT) and the other with 198 women who received a placebo. All of the pregnant women knew that they were infected with HIV, had consented to participate in the study, and knew to avoid breastfeeding (all were provided with infant formula and counseled not to breastfeed -- none did so).

Following this advice, only 35 of the 199 liveborn children (there was one set of twins) in the placebo group were documented to be infected.

If they had breastfed, instead of 35/199 or 17.6% being infected, the percentage would likely be in the 25-35% range. Following the administration of AZT and advice to not breastfeed, only 17 of the 196 live born children (again, there one set of twins) were documented to be infected in the treatment group. The authors state that the study is still not complete and more analysis needs to be done, but it appears that the treatment group had about half the risk of viral transmission as the placebo group.

3. Dr. Thomas states that Glaxo Wellcome is the only company that now sells AZT and implies that support of AZT is "akin to an unethical product endorsement." Following this advice would be very inappropriate. Through the recent efforts of UNAIDS, Glaxo has offered to sell the drug for a deep discount, making it available to many more pregnant women. Failure to promote the use of AZT would reduce the sales of Glaxo (which Dr. Thomas implies is beneficial) but would also result in many more infants being infected (which I am sure he, like others, would view as harmful).

While some might prefer waiting until all scientific facts on the Thailand study have been published, confirmed by additional investigations in other locations, or wait until other companies are able to produce drugs similar to AZT, there is a epidemiologically-measurable cost to such waiting. Fortunately, health officials in Thailand have decided that enough information is at hand, and are moving forward to save the lives of additional infants with AZT treatment during their mother's pregnancy. Others would do well to follow their lead, and develop action-oriented public health programs of their own that feature HIV detection among pregnant women, and low-dose AZT treatment for those found to carry the virus.

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