Magical thinking? FEM-PrEP trial may have failed because participants used testing as prevention

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While the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) featured news from two trials of pre-exposure prophylaxis (PrEP) that had positive results, it also featured an analysis of the reasons why another trial may have had a negative one.

The FEM-PrEP trial took place in four sites in South Africa, Tanzania and Kenya and enrolled 2120 women aged 18 to 35 who were given either tenofovir (Viread) plus emtricitabine (FTC, Emtriva) as PrEP or a placebo.

Its results, announced in April 2011, were a disappointment as the women allocated to tenofovir/emtricitabine had no fewer HIV infections than the women on placebo. Analysis of drug levels in subjects showed that adherence had been very low: fewer than 40% of the women involved had taken any drug in the 48 hours before a drug test, and only a quarter had taken their pills daily.



A product (such as a gel or cream) that is being tested in HIV prevention research. It could be applied topically to genital surfaces to prevent or reduce the transmission of HIV during sexual intercourse. Microbicides might also take other forms, including films, suppositories, and slow-releasing sponges or vaginal rings.


A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.


To eliminate a disease or a condition in an individual, or to fully restore health. A cure for HIV infection is one of the ultimate long-term goals of research today. It refers to a strategy or strategies that would eliminate HIV from a person’s body, or permanently control the virus and render it unable to cause disease. A ‘sterilising’ cure would completely eliminate the virus. A ‘functional’ cure would suppress HIV viral load, keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled and prevented from causing any illness. 


A patient’s agreement to take a test or a treatment. In medical ethics, an adult who has mental capacity always has the right to refuse. 

retention in care

A patient’s regular and ongoing engagement with medical care at a health care facility. 

While there were also concerns that the injectable contraceptives many participants took may have increased the risk of HIV infection, it looks as if in the main the subjects of the FEM-PrEP trial decided oral PrEP was not for them. And yet retention in the study was excellent: at the end of the trial, 82% of those who started had continued to attend monthly trial visits.

A series of qualitative interviews with a randomly picked 5% of trial participants suggests that women joined the trial for reasons other than PrEP and that the thing they valued especially was having a monthly test for HIV. In addition, they used the test, and participating in the trial itself, as a way of getting reassurance that they did not have HIV. The trial itself, in the minds of the women, became the prevention method offered.

“It’s magical thinking,” presenter Christina Wong of FHI 360, who co-ordinated the trial, commented to “We should discuss how to better incorporate participants' reasons for trial participation into trial design,” she said.

What participants said

The researchers analysed the reasons participants gave for enrolling and remaining in the trial and divided them into direct benefits, altruistic benefits (helping others), and other reasons – including, in South Africa, the 150 rand (nearly £10) they received each trial visit, which has been questioned as a motivator.

In fact, only two women mentioned the financial compensation as a reason for enrolling or continuing: one did say “To be honest, I like the R150,” but this was not a common topic in the interviews.

The most common reasons for joining and participating in the trial were other direct benefits.  Sixty-four per cent mentioned these as a reason for enrolling and 49% as a reason to continue. The three benefits most commonly cited were the monthly HIV test (32% of participants said this was an important reason for joining the trial), the support the trial gave them to stay negative (25%) and the monitoring offered for other health problems (22%).

One participants said of the regular HIV tests: “I decided to join the clinical trial because I had been tested for HIV a long time back and now I wanted to know my HIV status.”

Another gave as a reason for continuing: “I feel comfortable knowing my status. So, every time I come here, the reason is that I wanted to get tested and know my status.”

Once duly reassured, the participants felt, the support and education the trial offered gave them the motivation, in itself, to stay HIV negative. They also saw it in broader terms, as a valuable educational experience.

One said: “What really made me join this study is that I saw that I will get different teachings…The first time I came, the education I was given, my heart just liked it. I saw that I should just continue being in this research because it’s something that is going to help my life.”

Participants also cited the supply of free condoms and the supply of PrEP pills as reasons to join and stay in the trial, but saw these as just one of a series of prevention aids the trial offered, not necessarily its main point.

Twenty-two per cent said another reason to join the trial was the free medical monitoring it offered.

One said: “When you are not in a study, you cannot just go to a clinic and say ‘I am going to test for HIV and all these tests.’ You can’t just take your money and go to the doctor to check yourself up…[here], they check the whole body so I get to know about my life, they even check my womb, everything.”

Helping others was also cited as a common reason to join and remain in the trial: 30% gave it as a reason to both join and to remain in the trial and it became more important as a motivator, relative to direct benefits, as the trial went on, though the direct benefits continued to be the primary motivator.

“Participants knew someone who has HIV or died from HIV, and wanted to help prevent this disease,” said Christina Wong, “or they wanted to help women in particular, or wanted to help their children in the future.”

One said: “I want to see as years go by a cure being found for HIV, because many people die from HIV and AIDS. I've lost many family members because of this disease. So I care. I want to see at the end, something be found that can be able to cure or to prevent this disease.”

"Preventative misconception" in trials

Christina Wong commented that the reasons given were similar to a study of the reasons joined another trial of a microbicide, the HPTN 035 trial of the non-ARV-based microbicides PRO2000 and BufferGel.

The author of that study, Cynthia Woodsong, found that many participants gave the main reason to join the trial the hope that the trial itself, regardless of the microbicide offered, would somehow protect them or their partners. She described this as “preventative misconception”, and notes that researchers became concerned about participants’ understanding of what was offered even before the trial concluded.

Wong noted that this differed from vaccine trials, where participants had mainly given altruistic reasons for joining the trial, being aware the candidate vaccine might not offer any direct benefit.

These results and the ones from FEM-PrEP indicate that exactly how the trial is promoted and described, and the benefits it offers and does not offer, need to be carefully explained to would-be participants  in advance of obtaining their consent for enrolment.


Wong C et al. Participant motivation for enrolling and continuing in the FEM-PrEP HIV prevention clinical trial. Seventh International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Kuala Lumpur, abstract WEAC0104, 2013. View the abstract and presentation slides on the IAS conference website.