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  • A long-acting formulation of HIV pre-exposure prophylaxis (PrEP) has been approved in the U.S.
  • Long-acting options may help to increase the use of and adherence to PrEP among some people
  • A research simulation found that long-acting PrEP could reduce new HIV infections by up to 54%

Over the past decade, HIV pre-exposure prophylaxis (PrEP)—which involves taking specific anti-HIV drugs prior to and after sex to reduce one’s risk of HIV infection—has been gradually rolled out across many high-income countries. Regular medical appointments and lab testing are part of the care involved with the use of PrEP.

In clinical trials and in the community, PrEP has proved highly effective when used as directed, particularly among gay, bisexual and other men who have sex with men (MSM).

In most high-income countries, the mainstay of PrEP has been a combination of two drugs—tenofovir + FTC—taken in pill form.

Injectable PrEP with long-acting cabotegravir

Last year the options for PrEP expanded in the U.S. with the approval of a long-acting (LA) injectable formulation of a drug called cabotegravir (sold as Apretude). After initial dosing, this drug is injected once every two months deep into the muscles of the buttocks. Apretude has not been approved in Canada, the European Union, the UK and other high-income regions and countries. This is because at publication time the manufacturer, Viiv Healthcare, for reasons that are unclear, has not submitted a dossier on the drug to regulatory authorities.

Lenacapavir – potential for long-acting PrEP

Another pharmaceutical company, Gilead Sciences, is testing the experimental anti-HIV drug lenacapavir in different populations: people without HIV to reduce the risk of infection with this virus and people with HIV for use as part of combination treatment. Earlier this year, clinical trials with lenacapavir had been suspended due to issues with the glass vials in which it was packaged. However, those issues have been resolved and the drug has resumed its place in clinical trials. In Canada, lenacapavir is likely to be approved for use as part of combination HIV treatment in late 2022. However, lenacapavir is not likely to be approved for HIV prevention for at least a couple of years, as clinical trials for prevention are ongoing. A major reason for the growing interest in lenacapavir is that after initial oral dosing this drug only needs to be injected once every six months to maintain levels in the body. Lenacapavir is injected just under the skin. Lenacapavir belongs to a class of drugs called capsid inhibitors. ViiV is in the early stages of developing a capsid inhibitor.

Islatravir and related compounds

A third company, Merck, initially had to suspend some clinical trials of its experimental anti-HIV drug islatravir. Interim analyses found that exposure to islatravir reduced the level of a group of white blood cells called lymphocytes in some participants in clinical trials. Merck has resumed clinical trials using lower doses of islatravir. Part of the reason islatravir was of interest is that, in theory, it had potential for infrequent dosing. Merck has recently announced that it is also developing another anti-HIV drug code-named MK-8527. This drug may have potential for infrequent dosing. However, at this time, the focus of research on MK-8527 will be safety.

Profit and health

Thus, it is possible that by 2025 there may be at least one option for LA PrEP. At this time, medicines for human, animal and plant health (in industrial agriculture) are developed largely by for-profit corporations. In human medicine, this is particularly the case for the fields of cancer and HIV in high-income countries. Therefore, a major factor underpinning decisions to invest in drug development is potential profit that could be made (once a drug has been approved by regulatory authorities). Market conditions can change and even if a drug for which there is an unmet need is successful in clinical trials, the company that sponsored the development of such a drug may not seek regulatory approval if it calculates that it will not make high levels of profit.

Projecting change

A team of researchers at Johns Hopkins University in Baltimore has developed mathematical models and tested computer simulations of the HIV epidemic in the U.S. The researchers were interested in assessing the potential impact of LA injectable formulations of PrEP on the trajectory of the HIV epidemic in that country. They collected statistical data on the HIV epidemic in the U.S. and used it to inform their model. They were interested in the period 2020 to 2030.

The researchers found that with current levels of oral PrEP use, the rate of new HIV infections would fall by almost 20% by the year 2030. However, if in addition to oral PrEP about 10% of people eligible for PrEP (but who were not using it) initiated LA injectable PrEP, the rate of new HIV infections could fall by as much as 36% by the year 2030.

Another scenario had 25% of eligible PrEP users (who were not currently using PrEP) initiate LA injectable PrEP, while the proportion of people currently using oral PrEP remained the same. The researchers found that the rate of new HIV infections would fall by up to 54% by the year 2030.

Study details

It is beyond the scope of this article to delve into the equations underpinning the simulation. However, here is some data presented by the U.S. researchers that was incorporated into the model:

  • In 2019, there were approximately 1.2 million people with HIV.
  • In 2019, there were 36,000 new HIV infections.
  • In 2019, two-thirds of new HIV infections were in gay, bisexual and other MSM.
  • In 2017, the U.S. Centers for Disease Control and Prevention (CDC) estimated that there were 1.1 million people who were eligible for PrEP but only 100,000 were using it.
  • A total of 44% of people who initiated oral PrEP discontinued it after one year.

The researchers ran many simulations about the impact of both oral and injectable PrEP. They focused on 32 towns and cities with relatively high rates of new HIV infections when assessing the impact of PrEP.


The simulations provided different results depending on different scenarios, as follows:

  • If everyone switched – if all of the people currently using oral PrEP switched to using only LA injectable PrEP, the simulation predicted only a modest (4%) reduction in the rate of new HIV infections by 2030
  • A 10% increase in oral PrEP use – if 10% of the people eligible for PrEP but not currently using it initiated oral PrEP, the simulation projected a 36% reduction in new HIV infections by 2030
  • A 25% increase in oral PrEP use – if 25% of people eligible for PrEP but not currently using it initiated oral PrEP, the simulation projected a 50% decrease in new HIV infections by 2030
  • A 10% increase in LA injectable PrEP use – if people who were currently using oral PrEP continued to do so and 10% of people eligible for PrEP but not currently using it initiated LA injectable PrEP, the simulation projected that the rate of new HIV infections would fall by 36% by 2030
  • A 25% increase in LA injectable PrEP use – if people who were currently using oral PrEP continued to do so and 25% of people eligible for PrEP but not currently using it initiated LA injectable PrEP, the rate of new HIV infections would fall by 54% by 2030

Bear in mind

The results from the simulation are interesting. A key finding was that people who used LA injectable PrEP stayed on it longer than people who took oral PrEP. The era of LA injectable PrEP has just begun and much remains to be understood about its deployment, discontinuation rate and other associated issues. As a result, the simulation may require refinement in the future as data from people on LA injectable PrEP accumulates.

Regardless of the mode of PrEP use (oral or injectable, daily or LA), if public health departments, healthcare providers and community organizations can dramatically expand the pool of people using PrEP, the simulation suggests that large gains can be achieved in HIV prevention over time.

Additional issues

Although LA injectable PrEP has much potential, it cannot solve every issue. The researchers stated that LA injectable PrEP “is unlikely to change racial disparities in HIV incidence unless it is specifically promoted to racial groups with a high burden of HIV.” There are probably other issues as well, such as subsidized access to PrEP.

A good step forward

No computer simulation can perfectly mirror reality. However, the present study is a good step forward at envisioning what might be possible in the field of HIV prevention in the U.S. Future refinements of the simulation need to consider issues such as the impact of the coronavirus pandemic and the ongoing outbreak of monkeypox. The researchers also need to incorporate findings that suggest that, at least in the past decade, people are more likely to be diagnosed earlier rather than later in the course of HIV infection. As well, the researchers need to incorporate the relatively rapid rate of HIV treatment (ART) initiation once a diagnosis has been made. The impact of ART is important, as randomized clinical trials have found that people who take ART and achieve and maintain an undetectable viral load with continued use of ART do not pass on the virus to their sexual partners.

The present study should inspire other researchers to consider creating computer simulations of the HIV epidemic in the U.S. to confirm the findings from the Johns Hopkins team. Also, researchers in Canada and other high-income countries could perform simulations and include different populations that are vulnerable to HIV so that the potential effect of long-acting PrEP and other HIV prevention interventions can be more broadly understood.

—Sean R. Hosein


Pre-exposure prophylaxis (PrEP)CATIE

Large study finds complications from HIV pre-exposure prophylaxis (PrEP) uncommonCATIE

Researchers study ways of expanding the pool of PrEP prescribers in OntarioCATIE

Canadian guideline on HIV pre-exposure prophylaxis and nonoccupational postexposure prophylaxis CMAJ

Alberta HIV pre-exposure prophylaxis (PrEP) guidelines (2021) – Alberta Health Services

Guidance for the use of pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition in British Columbia (2020) – British Columbia Centre for Excellence in HIV/AIDS

Pre-exposure prophylaxis: Guideline review for primary care practitioners in Saskatchewan (2019) – Saskatchewan HIV Collaborative

La prophylaxie préexposition au virus de l'immunodéficience humaine : Guide pour les professionnels de la santé du Québec (2019) – Ministry of Health and Social Services of Quebec (in French only)

Boston study finds Biktarvy useful for HIV post-exposure prophylaxis (PEP)CATIE News


  1. Balasubramanian R, Kasaie P, Schnure M, et al. Projected impact of long-acting injectable PrEP use among men who have sex with men on local HIV epidemics.  JAIDS. 2022 Oct 1;91(2):144-150.
  2. Merck. Merck to Initiate New Phase 3 Clinical Program with Lower Dose of Daily Oral Islatravir in Combination with Doravirine for Treatment of People with HIV-1 Infection. Press Release. 20 September, 2022.