With almost 5 million new HIV infections and 3 million AIDS deaths occurring every year worldwide – almost 600 every hour -, the development of safe, effective, and accessible prevention methods has become one of the most urgent global public health needs1. One innovative method, aimed at reducing HIV infection through chemoprophylaxis, is the use of the antiretroviral drug tenofovir (Viread), a nucleotide reverse transcriptase inhibitor produced by Gilead Sciences Inc. Tenofovir has been chosen as a promising agent for Pre-exposure Prophylaxis (PREP) therapy for several reasons: it is taken once daily, can be taken without food, and also has a strong safety record, limited side effects, and a favorable resistance profile in HIV patients.

Research in animals indicates that tenofovir used as a PREP may be effective in reducing the risk of HIV infection23, although recent data have questioned the longevity of tenofovir's protective effect if there is one4. In order to determine if tenofovir may prevent HIV infection in humans, the National Institutes of Health, the Bill and Melinda Gates Foundation and the Centres for Disease Control funded a series of randomized trials (See Table 1). The conduct of these trials have, however, received widespread criticism by activist groups citing ethical concerns and a lack of community involvement in the planning of the trials56. This emerging opposition has halted the progress of 2 PREP trials, in Cambodia and Cameroon, and threatened the stability of planned PREP trials, and related recruiting effort, in other developing nations7.

In order to identify all relevant media articles, we searched 3 media databases (POPLINE, PROQUEST and LexisNexis), 5 electronic medical databases (AMED, CINAHL, E-Psyche, EMBASE and MEDLINE) as well as extensively searched the Internet using Google from inception to March 10, 2005. Our specific search terms included, but not limited to: "tenofovir", "viread", "Gilead", "Cambodia" and "Cameroon." We limited articles to those published in the English language. We contacted advocacy agencies and FHI to determine recent interviews they may have provided. We additionally reviewed CDC factsheets.

To be included in our review, articles had to report on the trial controversy and closures in Cambodia or Cameroon. We included articles from any media source, but excluded non-media articles posted on Non-Government Organization (NGO) and activist websites as these contain mostly blogs or position papers and are not intended to be objective. We additionally excluded articles addressing the trial stopped in Nigeria, since this trial was stopped by FHI for logistical reasons, as well as the planned trials of PREP in other developing countries, because they have not been halted at the time we conducted our search 7.

Three authors independently reviewed articles and reviewed them for relevance (PW, BR, EM). Using content analysis, we developed a coding template and extracted the following information from each article: source, date, location of article, author of article, individuals cited, organizations cited, events reported, and source of evidence. We extracted data on the initial coding template through a first reading of the articles to identify major themes. We agreed on the theme categories through consensus. We then reread the articles and coded them appropriately independently, in duplicate. We focused on reporting the claims and counter-claims reported concerning the trials. We aimed to determine the extent to which media reports sought input from stakeholders. As much misleading information was available on the internet through web-blogs, we believed that contact with stakeholders would provide greater inferences into the actual reasons for contentiousness or conduct of the trials. We specifically determined how many articles reported speaking with the following individuals involved in the trial closures: activist groups, researcher groups involved in the trial, local ministry officials and participants. All disagreements were resolved by consensus.

Our systematic searches yielded 52 relevant articles addressing the trial in Cambodia. We excluded 22, leaving 30 reports, of which 6 are duplicates. In total, we included 24 distinct, original reports addressing the Cambodian trial 1516171819202122232425262728293031323334. We included 13 reports that specifically addressed the trials in Cameroon 333536373839404142434445.

The findings of this review should be of interest to clinical trialists, advocates and policy makers. The media are important communicators of information and can raise awareness of emerging issues concerning health and risk57 We observed that the media brought forth a variety of concerns related to the conduct of the trials in both Cambodia and Cameroon. In several instances these concerns were not supported by evidence and were possibly inaccurate. We also observed that the media involved stakeholders to a comparatively small degree, suggesting that the viewpoints they reported may not accurately represent the views of all those concerned about the conduct of the trial. Given the potential impact of the media reporting on the conduct of future tenofovir trials, the nature of their reporting deserves closer scrutiny.

There are several limitations to consider in interpreting our review. Although we systematically searched many databases and extensively searched the Internet, it is possible that we were unable to identify some reports. Our searches were limited to the English and French languages, and as both Cambodia and Cameroon have media in other languages, we may have missed articles published in their respective languages. We conducted a content analysis to identify issues that we deemed trial related. It is possible that other issues exist, and that other individuals were interviewed, but were not reported in the articles. There are also several strengths to consider in interpreting our review. This is, we believe, the first systematic review to assess media reporting related to the closed trials. We conducted extensive searches and extracted data independently, in duplicate, to remove investigator driven biases. We spoke with representatives from each stakeholder group to determine if they were aware of additional reports, as well as searched the CDC reports.

The media reports consistently reported concerns with ethical issues in the conduct of the trials. Both the Cambodian reports and the Cameroon reports cite access to appropriate standards of care for those who become infected during the trial and appropriate standard of prophylaxis. Indeed these same issues are being echoed in the impending trial of tenofovir in drug users in Thailand9. Further to this, most media reports regarding both trials reported that participants were not fully aware of the risks involved with participation. Clinical trialist's planning prevention trials, whether of chemoprophylaxis or microbicides should be aware that many populations are not in situations in which to make informed decisions about clinical trial methodologies and the risks related to trial participation. Enrolling these communities in developing nations requires the establishment of community advisory boards and gender advisory boards, to ensure that the information is being provided, and interpreted, in an accurate manner5859.

The tenofovir trial media attention does however, have implications for prevention trials, such as HIV vaccines. Prevention methods are urgently needed to stem the onslaught of new HIV infections. Novel interventions, such as vaccines, microbicides, or chemoprophylaxis, will all require clinical trial validation. The media reporting of the tenofovir trials may threaten trial recruitment and potentially stigmatize trial participation.

There are important qualitative differences between the media reports of the trial in Cambodia compared to the trial in Cameroon. It is important to note that the trial in Cambodia was closed before recruiting any participants, whereas the trial in Cameroon had met its recruitment goals (n = 400). Most criticisms regarding the trial in Cambodia related to a lack of access to adequate care during the trials and post-trial, for those who may become infected. These concerns for potential infections appeared to be the overriding concerns as activists cited that these trials would be conducted to a different level of protection and insurance if they were conducted in a developed country. The articles addressing the trial closure in Cameroon were somewhat different and were largely based on reports of trial misconduct, in the context of inadequate informed consent, inadequate access to counseling and inadequate access to male and female condoms. The trials did however; have overlapping concerns about the ethical standards for trials in developing nations compared to Western nations and the protection of the participants human rights.

The tenofovir trials raise important questions about the relationship between researchers, participants and activists60. With worldwide media attention, these trial closures demonstrate the ability of activists to engage the media and bring about important consequences for the conduct of trials. Activists are experienced at bringing about change and have strong lobbying potential that can impact researchers and the HIV community. The activist communities have substantial experience using the media to address topics of importance in HIV and are well-educated regarding ethical standards and trial designs. Indeed, it is important to note that several of the ethical issues raised in the media reports: standard of care, access to proven prophylaxis and access to treatment for seroconverters; have not yet been resolved within the academic community 6162.

In conclusion, our review identifies the heterogeneous reporting of issues related to these trial closures and the relatively poor involvement of stakeholders for the purpose of interviews. In several instances these concerns were not supported by evidence and were possibly inaccurate. However, the overall issues reported in the media reports is a sense of distrust and concern for the well-being of participants. Given the role of the media in reporting on the conduct of future prevention trials, serious initiatives are warranted to engage the media and preempt difficulties in the transference of information.

The author(s) declare that they have no competing interests.

EM, SS, EW conceptualized the study. EM, EW, SS, PW and BR carried out the searches and data abstraction. EM, EW, BR, PW, SS, and KW wrote the drafts of the manuscript. EM, EW, BR, PW, SS, and KW dealt with critical revisions and final submission of the manuscript. All authors approved the final manuscript.