Fear of side-effects the greatest barrier to long-acting injectable PrEP

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Fear of potential severe side effects may be the greatest barrier to long-acting injectable HIV prevention among men who have sex with men (MSM), followed by out-of-pocket costs, found a US study.

When examining relative importance of perceived barriers to long-acting injectable pre-exposure prophylaxis (PrEP), perceived side effects was the most important, representing 52% of the total relative importance, according to lead author Will Beckham, of Johns Hopkins University Bloomberg School of Public Health in Baltimore.

While out-of-pocket cost comprised 30% of the relative importance, other attributes were less important to this population, such as injection frequency (11%), stigma (5%), and service location (2%), according to data from an internet survey of MSM presented at the virtual International AIDS Society Conference on HIV Science.

Results from the HPTN 083 trial (HIV Prevention Trials Network) presented in July 2020 found that long-acting injectable PrEP cabotegravir was superior to oral tenofovir/emtricitabine (TDF/FTC, or Truvada) for HIV prevention, but long-acting injectable PrEP has yet to be approved in the US.

The authors used the American Men's Internet Survey, a large annual survey of 10,000 cisgender MSM in the US and territories. Participants were ages 15 and older, HIV-negative, and sexually active. Beckham's group then employed a discrete-choice experiment.

Beckham noted this methodology is commonly used to explore participants' preferences for a particular healthcare service or product. Participants are presented with a series of product features or attributes with varying levels, which allows researchers to examine all attributes relative to one another, unlike a traditional head-to-head comparison.

Participants were presented with two choices, each with varying levels of these attributes, and asked which they would prefer.

“Choice A, for example, might be mild side effects, injection done every three months, pay $25 out of pocket, injection done at a private doctor's office and a medium risk … [of stigma] for being on PrEP,” Beckham said. Next to this he presented a Choice B, which was severe side effects, injection done every other month, $0 out of pocket, injection done at a pharmacy, and a low risk of stigma for being on PrEP. The data was based on how participants respond to different combinations with different levels of options.

After a question about how likely they would be to use long-acting injectable PrEP, those who answered “very unlikely” were removed, leaving 2,241 MSM. Fewer than two-thirds were younger than age 30, 63% were white, 78% had some college education, and 60% were urban/suburban. In the past 12 months, 84% reported having two or more male partners and 73% reported condomless anal sex. About three- quarters of MSM said they would be willing to use oral PrEP and 28% said they were using it currently.

Avoiding side effects was by far the most important barrier to use. Based on the responses, Beckham's group estimated that respondents would be willing to pay $84 for a “one unit change” in severe side effects, which were defined as needing to seek professional healthcare services to treat them.

Beckham encouraged implementing effective social and behavioural strategies to potentially encourage PrEP usage and effective communication of clinical data.

“Fear of side effects is going to be strong whether or not they reflect the reality of what the injection actually entails. We will have to address those fears and … perceptions if we want people to use injectables,” he said.

Beckham also emphasised the importance of out-of-pocket cost, which would be particularly relevant for youth, racial, and ethnic minorities, as well as those of lower socioeconomic status. Increased insurance coverage and other subsidies would help with these barriers, he noted.

MedPage Today reports that session moderator Dulce Ferraz, , said she was surprised that more respondents weren't concerned about stigma. Beckham responded that might be due to the “changing landscape”  of stigma in the US, where PrEP is now perceived more as “a good thing for gay men to do to protect themselves and others”. He also added that privacy might be a factor.

“Because it is injectable, it's easy to hide, so instead of having that daily pill at home that a partner might see in your medicine cabinet … it's something you can sneak away to the clinic, get it, and forget it,” Beckham said.

 

Original study details of HPTN 083

A Phase 2b/3 Double Blind Safety and Efficacy Study of Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC), for Pre-Exposure Prophylaxis in HIV-Uninfected Cisgender Men and Transgender Women who have Sex with Men

Published online at HPTN on 7 July 2020

Summary

What is HPTN 083?
HPTN 083 is the first study to compare the efficacy of CAB LA to daily oral TDF/FTC for HIV PrEP. HPTN 083 enrolled 4,570 cisgender men who have sex with men (MSM) and transgender women (TGW) who have sex with men at 43 sites in Argentina, Brazil, Peru, United States, South Africa, Thailand and Vietnam.

Why is HPTN 083 important?
For many people, taking a daily pill can be challenging. The development of safe and effective long acting alternative agents for HIV PrEP would increase HIV prevention choices and help those who find taking a daily pill challenging. Some people also may find periodic injections to be a more discreet form of HIV PrEP than daily pills and may prefer CAB LA for that reason.

Method
Participants were assigned randomly (by chance) to either the CAB or oral TDF/FTC group. Neither the participants nor the study team knows who was in which group. Participants in each group received both injections and oral tablets – each participant received one active drug and one placebo (no active drug) in order to maintain the blinded nature of the study.

Participants were randomized to one of two study arms and included three steps: Step 1 consisted of 5 weeks of daily oral CAB and a TDF/FTC placebo or 5 weeks of daily oral TDF/FTC and an oral CAB placebo; Step 2 consisted of 148 weeks of intramuscular CAB LA 600 mg every 8 weeks plus daily oral TDF/FTC placebo or 148 weeks of daily oral TDF/FTC plus an intramuscular CAB LA placebo every 8 weeks; and Step 3 consisted of an open-label daily oral TDF/FTC for 48 weeks after participants completed Step 2.

Results
On 14 May 2020 a Data and Safety Monitoring Board (DSMB) reviewed HPTN 083 study data and recommended that the blinded part of the study be stopped early for successfully meeting its specified objectives. The study results showed that CAB LA, administered every eight weeks, provided high efficacy compared to TDF/FTC. A total of 50 incident HIV infections occurred in HPTN 083, with 38 incident HIV infections in the TDF/FTC arm (incidence rate 1.21%) and 12 incident HIV infections in the CAB arm (incidence rate 0.38%): in other words, approximately three times the number of incident HIV infections were in the TDF/FTC arm than in the CAB arm.

The study sponsor, the US National Institute of Allergy and Infectious Diseases (NIAID), approved the decision to stop the blinded part of the study.

After a more extensive analysis of the interim study data, the regimen containing CAB LA was found to be statistically superior to daily oral TDF/FTC for PrEP among the cisgender men and transgender women who have sex with men enrolled in HPTN 083. A total of 52 incident HIV infections occurred, with 13 incident infections in the CAB arm (incidence rate 0.41%) and 39 incident infections in the TDF/FTC arm (incidence rate 1.22%).

The hazard ratio for the CAB versus TDF/FTC arms is 0.34 (95% CI 0.18-0.62), corresponding to a 66% reduction in incident HIV infections in study participants given CAB compared to TDF/FTC. These results were presented at AIDS 2020.

 

Full Medpage story – Survey Probes Barriers to Long-Acting Injectable PrEP for MSM (Restricted access)

 

See also: Understanding participant experiences and preferences in an injectable PrEP trial: A qualitative substudy of barriers, facilitators, and preferences for PrEP use among MSM and TGW

 

Original HPTN 083 trials (Open access)

 

See more from MedicalBrief archives:

 

HPTN 084 study: The promise of HIV prevention injections

 

Surprises in cabotegravir PrEP study

 

PrEP 'safe and effective for widespread use'

 

Beyond Truvada, what is the future of PrEP?

 


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