“Coming to the hospital every month, with people who work from 9:00 am to 5:00 pm…Waiting in line because they [medical team] are late, because there’s something which doesn’t work. When you are working, it’s just unmanageable. If it’s only once or twice a year, nobody sees anything, but if it’s every month, you arrive late at your office… It makes you too uncomfortable.” Isabelle, diagnosed with HIV in 1984.
“I would dream of a week without any drugs”. Pierre, diagnosed with HIV in 1988.
Isabelle and Pierre were participants in a French study that explored perceptions of injectable long-acting antiretrovirals among potential users, that is, people living with HIV taking oral HIV treatment and users of HIV oral pre-exposure prophylaxis (PrEP).
Recently published in AIDS Care, the study results demonstrate how complex the relationship of each individual to their HIV treatment or PrEP is in the real world. These findings help put into perspective the apparent popularity of the new mode of antiretroviral administration, as reported by clinical trials.
The study was conducted in Paris by a team of doctors and anthropologists with patients attending two HIV-care units for their HIV treatment or prevention. To be interviewed for the study, people living with HIV had to be stable on antiretroviral therapy, but otherwise were selected to have a diverse HIV treatment history (for example, time since diagnosis). HIV-negative participants had to have received PrEP for at least six months and to have regularly attended medical examinations. As far as possible, both groups of participants were selected to have diverse socio-demographic profiles (sex, age, professional level).
The one-hour interviews were performed following medical consultations at the HIV units, or at the participant’s home, or in a café. Interviews focused on participants’ experience with HIV therapy or PrEP, knowledge of new modes of administration, and willingness to adopt them. The idea of long-acting antiretrovirals, with injections every month or every other month instead of one pill a day, was presented by the interviewer. Also covered were other important issues such as the interviewee’s history of health and illness, experience with injection and perceptions of medical care.
Fifteen people living with HIV (nine men, six women) were recruited, of whom nine were born in France (two in the French overseas territories) and six in Africa. The majority (eleven) lived in Paris, the others in its suburbs. Median age in the group was 54 years. Just over half were heterosexual, and six out of the nine men were homosexual. Ten participants had stable jobs, while three were retired. Importantly, nine had been diagnosed as early as the 80s and the 90s.
As for the 13 PrEP users, all were male, 12 had sex with men, and their average age was 42 years. Most were single, lived in Paris and had a stable professional situation. They took PrEP daily, on-demand or alternately between these two options.
Participants were not “really in favour” or “really against” injectable long-acting antiretrovirals but used the interviews to discuss advantages, concerns and sometimes reluctance. As a matter of fact, they were often ambivalent as they addressed daily life with injectable medication, the specificities of this mode of administration and how they felt about it being experimental.
Injectable long-acting antiretrovirals in daily life
Both people living with HIV and PrEP users perceived injectable long-acting antiretrovirals as a simplification of their medication, as well as a way to keep their HIV status secret, be rid of the need to “think about it” every day and improve their adherence.
“To have a shot every two months rather than a tablet every day. Once every two months, a doctor’s appointment, click, it’s done, it’s over, we don’t think about it anymore, I think it would be the best thing!” Ricardo, PrEP user.
“That would not be bad… Especially since, as it would be done by a professional, you are not likely to forget it in fact… It changes a lot for your life comfort.” Salem, diagnosed with HIV in 1997.
Regarding daily life with antiretrovirals, participants’ comments were primarily based on their current experience with these drugs, which was typically described as “routine”, without discomfort or side effects. On the other hand, the fear of routines being disrupted, new side effects, poorer health and needing to attend multiple appointments was important among people living with HIV, particularly those who had a long and complex treatment history. For example, Isabelle said that she had experienced 12 different antiretroviral therapy regimens between 2003 and 2009. Now that her treatment was “stabilised”, she saw no “reason to switch”.
PrEP users, though welcoming the life-simplifying nature of injectable long-acting antiretrovirals, seemed to question the practicalities of injections (frequency, location, timing, etc).
Mode of administration
Some individuals living with HIV and PrEP users clearly preferred injectable to oral antiretrovirals, and positive prior experiences with injections made this preference more likely. However, for some others, bad memories of injections made them feel more reluctant about injectable long-acting antiretrovirals.
“I’m not in the mood! … [The oral tablet is] much simpler than a shot. Injections, I’ve had enough. With the possible risks of damage to a vein, or getting an abscess…” Ferdinand, a person living with HIV born in west Africa who received injections “at the time when syringes were sterilised and re-used.”
The invasive nature of injectable long-acting antiretrovirals – leaving enough active drug in the body for several weeks, without the individual being able to intervene, for example by changing the time he takes his pills – was an additional factor of anxiety in both groups of participants. They felt a loss of control and autonomy towards their medication.
“Already one, then two and three drug intake, and that’s it. I feel like I’m going to die. Can you imagine a drug staying a month [in my body]? How can you do that if you can’t stand it?… it’s unbearable!” Isabelle, person living with HIV.
This concern is in line with what has previously been described, for example in a study on prolonged-release neuroleptics in schizophrenic patients.
“[With the tablet], I can stop for one reason or another, it won’t be possible with injectables…” Anthony, PrEP user.
An experimental medication
How comfortable were participants about injectable long-acting antiretrovirals being an experimental intervention? In relation to this theme, there seems to have been less divergence of opinions.
Among people living with HIV and PrEP users, the interest for long-acting antiretrovirals was conditioned on their doctor’s confidence and information about the efficacy of the treatment. Those who were reluctant questioned the medication’s effectiveness. Fears of being used as guinea pigs were reported by some PrEP users.
“I let others test it, there are plenty of them who would try, I’m sure, and then we’ll see.” Isabelle, person living with HIV.
“I’ll see the benefits and then I’ll decide.” Olivier, PrEP user.
According to the investigators, this concern not only reveals distrust in pharmaceutical products but also participants’ need to be reassured. Doctors’ practices and recommendations are likely to have a strong influence on whether or not patients decide to take long-acting antiretrovirals.
More options for treatment and prevention
“If the doctor tells me: 'a shot every two months (…) would not be a problem', I will go! If he says, 'Well, it’s better to keep your medicine [tablet],' I would follow him. I am new in this field, so I’ll ask the question and decide.” Bruno, PrEP user.
Will patients taking injectable long-acting HIV medicines end up being disempowered with regards to their treatment or HIV prevention? As well as the deference to medical expertise expressed by some interviewees, injections, so far, cannot be self-administered. Stable patients will require far more clinical appointments than for current oral antiretrovirals.
"The real-world character of this study allows for more nuanced views of long-acting ART than the 'high acceptability' reported from clinical trials."
The question of disempowerment is among the key issues that remain to be explored, along with scepticism, hope and mistrust expressed by participants and observed in many previous investigations.
“These ambivalences, even if they were predictable, are significant”, say the researchers, who add that they are “reflected in a general wait-and-see attitude.”
For the investigators, the results reiterate “the importance of considering people’s experience over time in order to better understand their conceptions and use of medications.”
“The use of the expression 'acceptability' to problematise long-acting antiretrovirals conceptions is, in itself, too restrictive and binary,” they continue. “It is not the issue of '(non) acceptability' of this treatment that is raised by participants, but rather they consider it in the light of their current and past lives and their broader representations and relationships to medical knowledge, practice and institution.”
Clearly, the real-world character of this study allows for more nuanced views of long-acting antiretrovial therapy than the 'high acceptability' reported from clinical trials, where study participants’ motivation, and perhaps enthusiasm, to test a new way to receive HIV medicines cannot be ignored as a possible bias.
Nevertheless, the researchers also acknowledge that long-acting antiretrovirals can be an interesting alternative for some people, in terms of treatment simplification, and allow for more individualised treatment or prevention. In their conclusion, they suggest that injectable long-acting antiretroviral therapy may be a good opportunity to increase the range of antiretroviral options “according to the user’s situation, constraints, experiences, needs, practices or lifestyle at a given time”.
Carillion S et al. Perspectives of injectable long acting antiretroviral therapies for HIV treatment or prevention: understanding potential users’ ambivalences. AIDS Care 32: 155-161, 2020.