From “good news” to “failure”: how French participants experienced an HIV remission trial

Treatment resumption was the most difficult phase for participants who stopped HIV treatment in a trial aiming to find post-treatment controllers, a study published in the journal AIDS found. All who had to restart treatment after their virus rebounded felt disappointed and most saw it as a failure. Some participants said their healthcare providers had framed the invitation to join the trial as “good news”, only to describe their return to treatment as a “failure”.

“Let's put it this way, yes, it's a failure, and so yes, I think they [the healthcare providers] were the first to say it, but that's how it went, and they also admitted that they were disappointed and that I wasn’t alone. They said, ‘[...] we’re also really disappointed’”.

For most of those whose viral load shot up quickly, restarting treatment brought back memories of their diagnosis period and for one, raised questions about their acceptance of their HIV status.

“It's... there's a lot of memories coming back, and so it's a bit hard... it's like reliving it all a second time, exactly [n] years later, almost the same thing, basically.”

Some participants even feared their viral load would not become undetectable again after restarting ART and were impatient for their results.

The study authors, Dr Sarah Lefebvre of Aix-Marseille University and colleagues, say the findings show the need to offer psychological support throughout HIV cure and remission trials. They also urge healthcare providers to choose their words carefully when inviting people to join and when treatment has to be started again.

Background

Most HIV cure and remission trials ask participants to stop treatment for a time (known as an analytical treatment interruption), to see whether the approach being tested helps them keep the virus under control. The French ANRS-175-RHIVIERA-01 trial did not test an experimental treatment. Instead, it recruited people with two characteristics that researchers believe may help the body control HIV once treatment is stopped: one, they had started ART during acute HIV infection (the first few weeks after acquiring HIV); and two, they carried a particular genetic profile that researchers think may help the immune system control HIV.

The trial aimed to enrol at least 20 people but only 16 took part. Eligible individuals were invited to participate by their HIV physician and followed up by their usual HIV care teams.

After participants stopped treatment, their viral load was monitored frequently and treatment was restarted if viral load went above 10,000 copies/ml and a second test within a week confirmed it. Other clinical factors and participants’ own wishes could also lead to restarting. Those who still had the virus under control after 48 weeks could decide with their doctor whether they wanted to restart.

The researchers interviewed 13 of the 16 people enrolled in the trial, three of them women, about three months after they joined. They also interviewed three men who were invited but chose not to take part. The interviews took place between June 2023 and February 2024. Participants had a median age of 51 and had been diagnosed with HIV a median of 10 years earlier. At the time of their interviews, five had been off treatment for a median of 12 weeks, and eight had restarted ART about four weeks earlier.

Results

Those who agreed to participate acknowledged the importance of HIV research and trusted their HIV doctors, most of whom had cared for them since diagnosis. This relationship gave them a sense of moral obligation, and they said they almost always agreed to join HIV trials when asked. They also hoped they could stop taking treatment for good.

“They [HIV healthcare provider] suggest something to me, and I go along with it without hesitation [...] I know how competent they are, I know their approach, it’s great, let’s do it! They don’t lie either, they don’t give false hope.”

Those who declined felt they would gain nothing personally from taking part, and that any real benefit would go to research. They found the follow-up appointments too demanding and the interruption too risky.

“Our lives are governed by this disease, and so we [he and his partner] said to ourselves, maybe we’ll go for it, but because of the risk of a recurrence of the virus without us knowing, even though we’d have blood tests and check-ups every week, we decided it was a bit risky.”

Most participants felt well and enthusiastic after stopping ART. All women, but none of the men, also described a sense of “relief”, as they no longer had to deal with daily pills or the psychological weight that came with them.

“[I felt] great from one day to the next! In fact, I still have the box [of ART pills]; I brought them back [to the healthcare provider’s office], and then Professor [Name] said, ‘No, no, keep them, you never know, keep them.’ [...] And then I didn’t miss [having to take] them at all!”

When the virus rebounded

Participants’ genetic profile, and the fact that their own doctor had invited them, strengthened their hopes of becoming post-treatment controllers. Two were convinced they would. A third believed their viral load would not rebound at all, because it had been undetectable for so long that they felt the virus “did not exist anymore” in their body. But most saw their viral load rebound to some degree.

“When the rebound started, even before the blood test, I told the nurse, ‘This isn’t good’, because I recognised it. You know your body, somehow. The fatigue, some things just aren’t right. And sure enough, with regard to the blood test results, they said, ‘Yeah, there’s a rebound alright.’’’

All participants thought about the risk of passing on HIV. Some were already using condoms consistently, had partners taking PrEP, or were not sexually active, while others started doing one of these. One participant felt anxious after having sex with a partner on PrEP once his viral load was detectable again:

“It was written in black and white [in the informed consent form] that I could have sex without a condom with someone taking PrEP, and that’s what I did, but the very next day, or even that same evening, I started to feel anxious, telling myself that what I had done was completely irresponsible.”

How people experienced restarting treatment depended partly on how their virus rebounded. One participant, told to restart after a small rebound that stayed stable for several weeks, waited two days in the hope that their doctor would change their mind and let the interruption continue. Another felt prepared, having had a small rebound before a larger one that meant restarting. A third, with a similar experience, questioned the point of waiting after the first rebound. Once back on treatment, one participant asked for weekly rather than monthly viral load tests.

All participants were satisfied with their decision to take part. Most of those who restarted treatment still felt they had helped advance science, although two said they would not do it again.

Conclusion

The authors suggest that because the trial relied on participants’ genetic profile and early treatment rather than an experimental drug, it may have raised their hopes of controlling HIV and deepened their sense of failure when that didn’t happen. As the consent form gave no indication of how likely success was, they say future trials should spell out the expected outcomes, or say plainly when these cannot be estimated. They add that providers’ own emotional investment in these trials deserves attention, as well as gender differences in how participants experience them.