CHAPTER 6

In this article, we will mainly discuss the issue of so-called mother-to-child-transmission (MTCT/MTC), given the extraordinary volume of publicity around this matter. In this regard, we will concentrate on the drug "Nevirapine", which is said to be the most effective for this condition, the cheapest and the easiest to administer.

On HIV/AIDS treatment generally, we will only cite some comments made by people who should know what needs to be known about this matter, namely, the scientists.

In its edition of May 10, 2001, The New York Times reported that:

" A leading maker of drugs that fight AIDS, the Agouron Pharmaceuticals division of Pfizer, and its agency, CCA Advertising in New York, are changing a consumer campaign they recently introduced for the drug Viracept. They are adding cautionary words that such drugs are not a cure for AIDS nor do they prevent the spread of HIV, the virus that causes AIDS. (Our emphasis.)

" The change is coming two weeks after the (US government) Food and Drug Administration sent letters to eight makers of anti-AIDS drugs, including Agouron, warning that these products could no longer be advertised without noting their limitations."

A press statement released by the US government health agencies on February 5, 2001, quotes Dr Fauci, director of the National Institute of Allergy and Infectious Diseases, as saying:

" Although antiretroviral therapy has provided extraordinary benefits to many patients, we know we cannot eradicate HIV infection with currently available medications.We are very concerned about a number of toxicities associated with long term use of antiretroviral drugs," says Dr Fauci. " Particularly alarming is the alteration of fat metabolism that can emerge during treatment. We are seeing an increasing number of patients with dangerously high levels of cholestorol and triglycerides.The bad news is that we must now find ways to deal with unanticipated toxicities, including the potential for premature coronary disease."

On February 7, 2001, Reuters reported:
" One of the first studies to look at the success of HIV treatment in inner-city patients from the time of diagnosis reveals a dire situation, a doctor working in Atlanta, Georgia, said here on Tuesday at the 8th Conference on Retroviruses and Opportunistic Infections. His study found that only 1 in 10 patients newly diagnosed with HIV achieved a reduction in virus in blood to "undetectable" levels - a major goal of treatment.

" One year after being diagnosed, 24 patients (18%) had died, del Rio reported. Of the 103 eligible to attend an outpatient clinic, the majority discontinued treatment after a few months.

" Nobody has really looked at the number of HIV-infected patients who achieve successful viral suppression with antiretroviral therapy starting from the time of diagnosis, del Rio told Reuters Health. Other studies have looked at the success of antiretroviral therapy in those patients who remain in care.

" 'What is striking to me, is that we think that those are the problems of Africa - but they're the real problems of our country. I tell people I work in a developing country called inner-city Atlanta,' del Rio said.' "

In "The AIDS Reader" 11(5): 236-237, 2001, its editor, Jeffrey Laurence, MD, writes:

" One must recognise that few clinicians anticipate that current ART (anti-retroviral therapy) regimens will extend the lives of HIV-infected patients more than a few years. Viral resistance and drug side effects undermine their utility. Indeed, in 1 of the 2 US economic studies, quality-adjusted life expectancy rose only 1.84 years for those initiating ART at higher CD4 cell counts; for those with low CD4 cell counts, it was not much better. Although this degree of life gained proved similar in magnitude and cost to that of thrombolytic therapy in myocardial infarction, such comparisons are irrelevant where more than 90% of HIV infections occur - in the developing world."

In another report dated May 25, 2001, Reuters said:

" Treatment with highly active antiretroviral therapy, or HAART, often damages the liver, leading many HIV-infected patients to halt treatment, according to study results presented in Atlanta this week.

" Regardless of drug class or combination, there appears to be 'an across-the-board high rate' of severe liver toxicity.

" Regimens that contained drugs called nonnucleoside reverse transcriptase inhibitors, especially nevirapine and efavirenz, were particularly hard on the liver.In November, the US Food and Drug Administration issued an alert for nevirapine based on reports of liver toxicity." (Our emphasis.)

Addressing the 39th Annual Meeting of the Infectious Diseases Society of America on October 25, 2001, Dr William G. Powderly, said:

" The safety of PEP (postexposure prophylaxis) was called into question earlier this year with reports of nevirapine-associated liver toxicity in otherwise healthy recipients, resulting in a recommendation that nevirapine not be used for PEP."

During the Durban XIII International AIDS Conference in 2000, the Chicago-based NGO, the International Association of Physicians in AIDS Care (IAPAC), issued the following statement, datelined "Durban, South Africa, July 11:

" Today researchers at the XIII International AIDS Conference presented preliminary data suggesting didanosine (Videx, also known as ddI) and stavudine (Zerit, also known as d4T) are safe, effective and tolerable alternatives to existing drug therapies in preventing mother to child transmission (MTCT) of HIV. Videx and Zerit are part of the reverse transcriptase inhibitor class of anti-HIV drugs and are proven to safely reduce HIV replication among infected adults and children. (Our emphases).

" The AI455-094 pilot study conducted at the Chris Hani Baragwanath Hospital in Soweto, South Africa randomised 373 HIV-1 infected pregnant mothers to an orally administered regimen of ddI, ddI+d4T, or zidovudine (AZT).
" These early data show the potential of Videx and Zerit to be safe, tolerable and effective in preventing the transmission of HIV from infected mothers to their unborn children when compared to existing medical interventions," said Dr Glenda Gray, co-director of Perinatal HIV Research Unit at Chris Baragwanath Hospital in South Africa.". (Our emphasis).

" Zerit and Videx are manufactured by Bristol-Myers Squibb Company, a global health and personal care company whose mission is to extend and enhance human life." (Our emphasis).

On January 8, 2002, the US Wall Street Journal reported as follows:
" While the Food and Drug Administration (FDA) conducts a review of the two products, Bristol-Myers Squibb has issued a warning to AIDS doctors around the world cautioning that two of its AIDS drugs, Zerit and Videx, should be used sparingly in pregnant women after the deaths of three expectant mothers who were taking the medications. An FDA official suggested it is possible that although toxicity problems affect other drugs in the nucleoside analogue class - which includes the GlaxoSmithKline drugs AZT and 3TC - the reaction to a particular enzyme is stronger for the two Bristol-Myers products than for other drugs in the class. The deaths could have far-reaching consequences than just the potential withdrawal of the drugs and the passing of the women: two of the deaths occurred in clinical trials abroad, with one of those deaths taking place in South Africa, where the issue of AIDS drugs is particularly volatile. The women died of lactic acidosis, a rare but recognised comp!
lication associated with the nucleoside analogue class, and seven other cases of nonfatal lactic acidosis have been reported among pregnant women taking either a combination of Zerit and Videx or of Zerit with 3TC." (Our emphases.)

Dr Glenda Gray features regularly in our media as a much-quoted and generally believed expert who denounces our government for its cautious approach to the widespread use of anti-retroviral drugs. In the IAPAC statement, she is quoted as endorsing Videx and Verit as being better than AZT and nevirapine in the context of MTCT.

She shared this view with the NGO, IAPAC, which described the company producing Videx and Zerit as "a global health and personal care company whose mission is to extend and enhance human life." Despite the undisguised competition with AZT in the IAPAC report, nothing is said about the legitimate commercial mission of Bristol-Myers Squibb to maximise its profit - to attend to the bottom line!

This company has now admitted that its products are not the "safe, effective and tolerable alternatives to existing drug therapies in preventing mother to child transmission (MTCT) of HIV" that Glenda Gray and IAPAC claimed they were. Pregnant women have died because they were subjected to these "safe, effective and tolerable alternatives"! Reportedly, one of them is a black woman, on whom Glenda Gray experimented with toxic drugs at Chris Hani Baragwanath Hospital.

Interestingly and ironically, this year the US Kaiser Family Foundation (KFF) conferred the Nelson Mandela Award for Health and Human Rights on Dr Glenda Gray (and Professor James McIntyre) for the supposedly 'outstanding' work she has done on MTCT. Nothing was said of the women who died!

Of Gray and McIntyre the KFF says:

"Dr Glenda Gray and Professor James McIntyre are co-founders and co-directors of the Perinatal HIV Research Unit at the Chris Hani Baragwanath Hospital, the largest in the world.The Perinatal HIV Research Unit is one of the world's leading centers of excellence for research and implementation activities in the field of mother-to-child transmission of HIV and has been at the forefront of work in this field.Responding to the changing needs around HIV/AIDS, the Unit has expanded to undertake work in antiretroviral treatment for adults and children, psychosocial support issues, HIV and tuberculosis and HIV vaccine trials.The Mandela Award.is given annually in recognition of extraordinary dedication and achievement in improving the health of the disadvantaged populations in South Africa and the United States."

Bristol-Myers Squibb must have been mightily pleased that their own Glenda Gray, enthusiastic promoter of Videx and Zerit, was honoured with so prestigious an award for improving the health of the disadvantaged populations in South Africa and the United States!
A number of questions that demand urgent answers arise in the context of the foregoing.

Why was the South African and global public told lies?
Since Glenda Gray must be held accountable, how has this been expressed?

Since Chris Hani Baragwanath Hospital must be held accountable, how has this been expressed?

Since the Medicines Control Council (MCC), which presumably approved the Glenda Gray clinical trials, must be held accountable, how has this been expressed?

How has the Gauteng Provincial Government accounted for its own conduct in this affair?

How have the national Ministry and Department of Health for their own conduct in this affair?

Have Videx and Zerit been licensed by the MCC for any indication, and if so, on what evidence?

What reports, in any, have been submitted to the MCC on the safety of these drugs if they are generally available in our country?

People have died as a result of using these drugs. The highest US regulatory authorities have instituted processes to study their impact. As of now, we do not know what the WHO and UNAIDS have to say.

But we need to know what our own regulatory authorities have to say. We also need to know whether our own health authorities have communicated to everybody concerned the substance of what the Wall Street Journal reported. What are the answers to all the questions that have been posed?

Last year, the periodical ANC Today posed other questions relating to another clinical trial conducted in our country. This concerned a microbiside that was touted as being potentially effective in the context of MTCT.
We quote this article in full because of the important issues it raises, especially in the light of what we have just said with regard to Videx and Zerit.

" DRUG TRIALS"HIV/AIDS, profit and fundamental human rights"THE STORY OF NONOXYNOL-9, known as N-9, an active ingredient used in chemical barriers to HIV and STD transmission, raises disturbing questions about research ethics, drug company profits and the role in Africa of international development agencies."Products designed to provide a chemical barrier to HIV and STD transmission, such as N-9, are called microbicides."

According to a circular of the US Centres for Disease Control (CDC), dated 4 August 2000: "From 1996 until May 2000, UNAIDS sponsored a study of the effectiveness of a gel which contained 52.5 milligrams of N-9., compared to an inactive gel. The study was conducted in several locations in Africa. Nearly 1,000 HIV-negative commercial sex workers were enrolled in the trial, and all women were counselled to use condoms consistently and correctly. In addition to condom use, the women were asked to use a vaginal gel each time they had intercourse.

Half of the women were provided a placebo (non-active) gel and half of the women received an N-9 gel.""Later, we will report on the results of this trial and the recommendations of the CDC. But before this, we have to give a short account of the history of N-9."

The conclusions of a 1992 N-9 study were published in the journal JAMA 1992 July 22-29; 268(4):477-82 and stated that: "Genital ulcers and vulvitis occurred with increased frequency in nonoxynol 9 sponge users. We (who conducted the trial) were unable to demonstrate that nonoxynol 9 sponge use was effective in reducing the risk of HIV infection among highly exposed women."

The trial referred to here was conducted among sex workers in Kenya in 1992."The results of another study were published in 1993 in the International Journal on STD and AIDS 1993 May-June; 4(3):165-70. This study concluded that: "The rate of epithelial disruption (genital ulcers) for women using N-9 4/day was five times greater than that of placebo users.""After another study conducted in Kenya, the Journal of Infectious Diseases 1991 February; 163(2):233-9, had concluded that genital ulcers were associated with increased risk of HIV-1 infection."

By the time UNAIDS began its studies in 1996, published scientific knowledge was that:

· genital ulcers increased the risk of HIV infection;
· the use of N-9 increased the incidence of genital ulcers; and,
· more frequent use of N-9 led to a higher incidence of genital ulcers.

"The August 2000 CDC circular to which we have referred said that the results of the UNAIDS trial were reported at the 2000 Durban International AIDS Conference, as follows:

"At the end of the trial, researchers found that the women who used N-9 gel had become infected with HIV at about a 50% higher rate than women who used the placebo gel. Further, the more frequently women used only N-9 gel (without a condom) to protect themselves, the higher their risk of becoming infected. Simply stated, N-9 did not protect against HIV infection and may have caused more transmission. Women who used N-9 also had more vaginal lesions, which might have facilitated HIV transmission."

"As we now know, these precise results of N-9, announced in 2000, were already publicly known by 1993. And yet UNAIDS began its trial in 1996, knowing that N-9 increased the risk of HIV infection, especially among those who might use the microbicide with high frequency, such as prostitutes."

Despite this knowledge, after the results were announced at the Durban AIDS Conference, Dr Joseph Perriens of UNAIDS could still say: "We were dismayed to find out that the group using N-9 gel had a higher rate of HIV infection than the group using a placebo."

"South Africa was one of the African countries in which UNAIDS conducted its trial. In a press release issued in Durban on 12 July, 2000, an organisation named AEGiS reported that the sites for the South African trial were Durban and Johannesburg.

"It also reported that the Principal Investigators responsible for the trial in these two cities were, respectively, Dr S. Salim Abdool Karim and Dr Helen Rees. At the same time as he was leading investigations into the efficacy of a chemical compound that was known to be extremely harmful, Dr Karim was head of AIDS Research at our Medical Research Council.

For her part, Dr Rees was Chairperson of the Medicines Control Council, the body charged with the responsibility of licensing drugs and medicines.

"The Business Day edition of 13 July 2000 reported Dr Rees as 'caution(ing) that the (negative) results were not conclusive and more work needed to be done on the issue. She pointed out, for instance, that it was possible that the group using the placebo (or substitute with N-9) may have been exposed to a more active microbicide.'

Presumably by saying that "more work needed to be done", she meant that more women needed to be exposed to the highly toxic N-9."In its edition of August 14, 2000, the Washington Post reported that:

"Two U.S.-funded studies involving nonoxynol-9 are underway in African women at risk of HIV. One, sponsored by the Agency for International Development to test the ability of nonoxynol-9 gel to prevent sexually transmitted diseases among a group of women in Cameroon, is due to be completed in September. The other, a study sponsored by the NIAID to look for protection against HIV in women in Zimbabwe and Malawi, is getting underway.

In light of the disturbing findings, reported last month at the 13th International AIDS Conference in Durban, South Africa, researchers have abandoned plans to test nonoxynol-9 in that study, said Ward Cates of Family Health International, a non-profit health research organisation that is co-ordinating the project.

Cates said there is no evidence that nonoxynol-9 is harmful to women when used as a contraceptive. Nonoxynol-9 is a detergent that is a contraceptive and a microbicide (or germ-killer).""It is puzzling that Cates should have found it necessary to promote the use of N-9 as a contraceptive, to soften the impact of the negative results announced in Durban.

"We do not know whether the US-funded trials in other African countries represent the "more work" to which Dr Rees referred."The gel mentioned in this article is produced by a US company called Columbia Laboratories Inc and is marketed as Advantage-S.

According to the Wall Street Journal, after the N-9 trial results were announced in Durban, Columbia shares 56%, to $5.75. The paper also reported that, nevertheless, President and CEO of the company, Mr William Bologna, said the negative N-9 results "may not be scientifically meaningful."

"In a press release dated March 20, 2000, Columbia Laboratories Inc said: "Prospective investors are cautioned that any.(Columbia) forward looking statements are not guarantees of future performance and involve risks and uncertainties, and that actual results may differ materially from those projected in the forward-looking statements (of the company). Such risks and uncertainties include, among other things, the successful timely completion of the study now being conducted by the UNAIDS group."

"Despite this cautionary note, Columbia Laboratories Inc could not avoid the retribution of either the market or its shareholders. According to the Wall Street Journal, not only did its share price fall dramatically, but it was also sued by its shareholders. The shareholders charged that insiders sold more than $1 million in stock at inflated prices before the results were announced.

"This is a highly disturbing story that has directly affected us as a country. It raises a number of questions that require urgent answers, some of which are:

· Why did the MCC approve N-9 trials knowing the toxic effect of this compound?

· Why did Drs Karim and Rees assume the role of principal investigator given the positions they occupied in the state medical institutes?

· What other trials related to HIV/AIDS have been and are being carried out in our country?

· What impact have these trials had on the health of the subjects recruited to participate in these trials?

· Why was the N-9 trial conducted only in African countries (and Thailand) and not the United States, which also has prostitutes?

· What measures have been taken to care for the prostitutes used in the trial, who suffered genital lesions and turned HIV-positive as a result of the use of N-9?

· What measures have been taken to care for other people whose health might have been adversely affected as a result of other trials?

· Why did UNAIDS decide to use our people as disposable objects who could be exposed to N-9, when UNAIDS knew that N-9 had been proved to be toxic?

· What steps has UNAIDS taken to look after the people whose health has been seriously undermined by its wilful activities?

· What will our government do to ensure that this serious matter is attended to?

· Has the attention of the UN Secretary General, the UN Security Council and the General Assembly been drawn to these UNAIDS activities?

· What steps has UNAIDS taken to ensure that especially the developing countries discontinue and do not allow any N-9 trials?

· What role did our Ministry and Department of Health play in the N-9 matter?

· What role have our Ministry and Department of Health played and are playing to ensure that ethical norms are observed in the conduct of all drug trials in our country, and that the poverty of our people is not exploited to test dangerous drugs here, in a manner that would not be allowed in the developed world?

· Has the informed consent of those who have been involved in the drug trials been obtained and what steps have been taken to ensure that those involved are truly properly informed?

· What measures have been taken to ensure transparency and a system of accountability with regard to the drug trials?

· Once the efficacy and safety of drugs previously tried in South Africa has been established, and these drugs accordingly registered, what steps have been taken to ensure that these drugs are available at affordable prices to our people?

"All these questions, bearing on the very lives of our people, require urgent answers."The story contained in this article speaks of our vulnerability as an African country to the anti-human activities of some corporate forces. It also speaks to our own capacity, as South Africans, willingly to co-operate in the promotion of these activities. It tells a story of how easy it is for some, further to entrench the abuse of already abused African women - this time in the name of science and health.

"Dr Rees, Chairperson of the MCC, argues that 'more work' needs to be done on N-9 because the negative results announced in Durban 'were not conclusive'. This sentiment is echoed by the CEO Bologna of Columbia Laboratories Inc., who says that these negative results 'may not be scientifically meaningful.'

"On the other hand, the CDC says: "However, given that N-9 has now been proven ineffective against HIV transmission, the possibility of risk, with no benefit, indicates that N-9 should not be recommended as an effective means of HIV prevention."

"What we ask is - what else about HIV/AIDS is more about profit and less about the health of our people. Time will tell."

To this day, the important issues raised in this article have not been answered. We do not know how many of our people have died as others, such as those at Chris Hani Baragwanath Hospital, conducted experiments on our people or "treated" them, relying on dangerously tendentious results of clinical trials and MCC approvals of trials sponsored by the pharmaceutical companies.