Effectiveness and frequency of dosing are the most important factors affecting acceptability of injectable HIV therapy, says US study

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Effectiveness and dosing frequency are the two key factors affecting the acceptability of long-acting injectable antiretroviral therapy, according to a small study conducted in the United States and published in AIDS and Behavior. Participants found injectable treatment moderately acceptable. The study included a broad spectrum of people living with HIV, including individuals with adherence problems, a likely target population for long-acting injectable therapy should it become available.

“Overall, our results suggest that as long as the targeted long-acting combination antiretroviral therapy works as well or better than daily pills and administration frequency is not too burdensome, people living with HIV may be willing to tolerate potential side effects, less preferred injection sites, and even moderate adverse site reactions,” comment the investigators. “It may even be that people living with HIV would even find regimens with comparable effectiveness to oral pills to be preferable under scenarios in which burden can be minimized.”

Larger studies are needed to build on these preliminary findings, suggest the authors. Such research could underpin information and education campaigns about injectable therapy.



In pharmacology, a medication which maintains its effects over a long period of time, such as an injection or implant.


Refers to the mouth, for example a medicine taken by mouth.

treatment failure

Inability of a medical therapy to achieve the desired results. 


Injected into a muscle.


Beneath or introduced beneath the skin, e.g. a subcutaneous injection is an injection beneath the skin.


Modern HIV therapy is very effective but relies on high and consistent levels of adherence. Some people find this challenging, leading to treatment failure, the development of drug-resistance and changes in treatment.

Long-acting injectable antiretroviral therapy is likely to become a treatment option in the near future and may be especially attractive to individuals who find adherence problematic. A long-acting combination consisting of cabotegravir and rilpivirine administered via intramuscular injection is currently in late-stage development. However, it has to be administered by a healthcare professional, in a clinic.

Long-acting therapies that could be delivered at home using subcutaneous injections are at an earlier stage of development. To see if such therapy would be acceptable to people with HIV, a team of investigators led by Dr Jane Simoni of the University of Washington, Seattle, designed a study involving 56 HIV-positive individuals. They were asked a series of questions about their interest in this type of treatment. These were structured in such a way that Simoni and colleagues were able to determine not only the overall acceptability of injectables, but also the factors that influenced individuals’ willingness to consider this therapy.

In the first set of questions, participants were asked to state preferences regarding location of injecting (home vs clinic); dosing frequency (every two weeks or every week); injections per dose (one vs two); injection pain (mild vs moderate); injection site reaction (mild vs moderate); and effectiveness (same as pills vs better than pills). In the second set of questions, they were asked to rate each of these scenarios in terms of acceptability (very unlikely, somewhat unlikely, neutral, somewhat likely, and very likely). The investigators assigned these ratings a score: “very unlikely” was zero, “neutral” was 50 and “very likely” was 100.

Recruitment took place in Seattle and Los Angeles in 2016 and 2017. The participants had a median age of 52 years, 71% were male, 76% were high school graduates, 73% were not working and over half were black or Latino. Adherence to HIV therapy was rated as good, very good or excellent by 79% of participants and an equal proportion had an undetectable viral load. A quarter were currently self-injecting either prescription medications or illegal drugs.

The overall acceptability score was 57.9 and was therefore somewhere between 'neutral' (score of 50) and 'somewhat likely' (score of 75). The investigators note that research investigating the acceptability of injectable HIV vaccines or PrEP produced similar scores.

The top-rated scenario (score of 68.8) was administration of the injection in a clinic, every two weeks, with two injections per dose, mild injection pain, mild injection site reaction and more effective than pills. The lowest rated scenario (score of 47.8) was home administration, once a week, two injections per dose, moderate injection pain, mild injection site reaction and as effective as pills.

"The overall acceptability score was somewhere between 'neutral' and 'somewhat likely'."

The two factors that significantly influenced the acceptability of long-acting injectables were superior effectiveness (p = 0.005) and less frequent dosing (p = 0.034).

Acceptability was moderated by several participant characteristics. Whereas individuals who had ever injected themselves were more likely to prefer to have the injection at home, those who had never injected themselves preferred to go to a clinic. Men were less concerned about injection pain than women. Superior effectiveness over pills was more important for individuals in work compared to participants who were not working.

Simoni and colleagues believe their research provides useful information on the acceptability of long-acting injectables. They call for larger studies to explore their preliminary findings, especially the attributes that affected acceptability, such as experience with injections, gender, education and employment. One limitation is that the majority of their study participants had good adherence to oral therapy.

“Improvements in adherence and persistence of antiretrovirals, in whatever format an individual prefers, are needed to meet global targets,” conclude the authors. “Acceptability research such as that presented here will help to ensure future options are amenable to people living with HIV, which will ultimately determine their success in sustaining viral suppression.”