Research Article: South Africa’s Experience of the Closure of the Cellulose Sulphate Microbicide Trial

Date Published: July 31, 2007

Publisher: Public Library of Science

Author(s): Gita Ramjee, Roshini Govinden, Neetha S Morar, Anthony Mbewu

Abstract: The researchers who conducted the cellulose sulphate microbicide trial share the lessons they learned from the trial’s early closure.

Partial Text: In sub-Saharan Africa, almost 60% of HIV infections are among women [1], and the number of new HIV infections in women worldwide continues to escalate. The high incidence of HIV in many African countries provides the optimum environment for research on technologies that could prevent women from becoming infected, including microbicides. In this article, we discuss the recent highly publicised closure of a trial of cellulose sulphate (CS), which we conducted. We discuss the impact of the closure on the participants, the community at the trial site and the public at large, the public health sector, national regulatory bodies, the media, and on other ongoing microbicide trials. The local lessons that we learnt from the closure may provide guiding principles for researchers and advocates in the HIV prevention field as a whole, who may face similar situations in the future.

Vaginal microbicides are products which, when applied to the vagina, may prevent HIV transmission. Such a product would be particularly valuable for women who are unable to negotiate condom use with their partners, since its use would be initiated by the woman. The concept of a vaginal microbicide was tested several years ago using an over-the-counter spermicide, nonoxynol-9, a surfactant that acts by disrupting cell membranes. The trial, conducted in several African countries, showed an increase in risk of HIV among women who used the product more than three times a day [2].

In early 2007, there was another huge disappointment. The randomised controlled trial testing 6% cellulose sulphate against a placebo gel for effectiveness against vaginal transmission of HIV, sponsored by the reproductive health research organisation CONRAD (http://www.conrad.org/), was stopped following recommendations by the DSMC after preliminary data review of 1,333 enrolled women from five sites (South Africa, Uganda, Benin, and two sites in India) suggested that there were more HIV seroconversions in the cellulose sulphate arm compared to the placebo arm of the trial. This unexpected outcome was a huge blow to the microbicide field as CS, a non-cyclic antimicrobial agent, had been tested in several safety trials previously and there were no concerns about safety based on these trials [16].

The HIV Prevention Research Unit (HPRU) of the Medical Research Council (MRC) in South Africa participates in all ongoing microbicide trials. Prior to the release of the press statement by CONRAD, we immediately developed a communication strategy to ensure that the information to stakeholders came from the local researchers (Table 1 and 2). Two days before the press release, we sent letters to the national and provincial departments of health, to the Medicines Control Council, which is South Africa’s drug regulatory authority, and to the ethics committee that had approved the trial, informing them of the trial closure with a request for an urgent meeting.

Despite these proactive steps to inform the wider community, some reporters wrote inaccurate and sensational stories. For example, on 4 February 2007, a national weekly newspaper ran stories with the headlines “Medical research trial guinea pigs contract HIV” [19] and “Study to prevent AIDS left me infected”. These reports included sensational statements such as “Hundreds of women in South Africa, Benin, Nigeria, Uganda and India, who are being used as human guinea pigs in the US-funded research on HIV prevention, are feared to have contracted the virus during the course of the trials” [19]. In fact there were 35 sero-incident cases among 1,333 participants across all the African trial sites. This alarmist statement instilled fear amongst all trial participants. Statements in the article saying, for example, that women felt “used and misled” [19] falsely implied that the conduct of the study was unethical.

Given that HPRU is involved in many clinical trials, the challenge was not only to address the closure of the CS trial, but to address the concerns of communities at trial sites of other ongoing microbicide trials in KwaZulu-Natal.

Participants from all other microbicide trials were affected by closure of the CS trial. Male partners who knew about women’s participation in other trials raised concerns that using “gel” increased HIV risk and did not want their female partners to participate in the trial. However, most women eventually decided to continue once they and their partners were counselled.

The outcome of the nonoxynol-9 trial in 2000 was a huge setback for microbicide research in South Africa. Health authorities, ethics committees, and drug regulators were concerned about the safety of microbicides. Although the nonoxynol-9 trial received negative press, it was not as damaging at the community level as the closure of the CS trial, perhaps due to higher awareness now of microbicide clinical trials in South Africa as a whole. Furthermore, the 2006 closure of the SAVVY trial did not have an impact on current trials, possibly because the closure was not safety-related.

The closure of the CS trial has underscored the challenges we may face in the event of early trial closure due to a negative outcome. We now have insights on how to prepare for outcomes of future HIV prevention technologies and, at a minimum, prepare strategies to ensure that the messaging and process of message delivery is developed with local investigators, participant communities, local regulatory authorities, and in-country media.

Source:

http://doi.org/10.1371/journal.pmed.0040235

 

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