ANC Today 16 - 22 Feb. 2001

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.