- Doctors studied a new HIV prevention drug that is injected into the muscle every two months
- 4,500 gay and bisexual men and transgender women entered the clinical trial of injectable cabotegravir
- The drug was found to be generally safe and significantly reduced the risk of HIV infection
Taking anti-HIV drugs prior to possible sexual exposure in order to reduce the risk of acquiring HIV infection is called pre-exposure prophylaxis (PrEP). Truvada, a pill containing two anti-HIV drugs (tenofovir DF + FTC), is approved as PrEP in Canada and many other countries. It is also available in generic formulations. A majority of clinical trials have tested Truvada as PrEP when taken as one pill every day. However, some clinical trials have found that taking it less frequently, on a schedule called “on-demand,” can also significantly reduce the risk of HIV infection.
Some people dislike taking pills and/or may not remember to take them. Pharmaceutical companies are developing drugs for PrEP that need infrequent dosing.
Long-acting PrEP
The pharmaceutical company Viiv Healthcare is developing a form of long-acting PrEP with a drug called cabotegravir. The drug is injected into muscle every two months. Long-acting cabotegravir is slowly released from muscle into the blood.
Study HTPN 083
The U.S. National Institutes of Allergy and Infectious Diseases (NIAID) sponsored a study called HPTN 083. This study recruited 4,570 HIV-negative people—mostly gay and bisexual men; about 12% of participants were transgender women. The study took place in South America, South Africa, Southeast Asia and the United States.
For the first five weeks of the study, participants took orally a combination of cabotegravir tablets and placebo Truvada tablets. This lead-in period was to ensure that participants did not develop side effects from cabotegravir. At the end of this time, participants were randomly assigned to receive one of the following interventions:
- long-acting cabotegravir injection + daily placebo Truvada pills
- injections of placebo + daily Truvada pills
Neither the participants nor clinic personnel knew who received which drug. The study began in December 2016.
Interim results
According to NIAID, a recent review of the study’s results by an independent data and safety monitoring board (DSMB) found that “long-acting cabotegravir was highly effective at preventing HIV in the study population.”
Some people became HIV positive during the study. These infections were distributed as follows:
- long-acting cabotegravir – 12 people
- Truvada – 38 people
Statistically, this suggests that cabotegravir was as effective as Truvada. Although the study was originally designed to show the superiority of long-acting cabotegravir, when the COVID-19 pandemic occurred it became increasingly difficult for participants to keep clinic appointments and many trial sites had to close. As a result, the scientists operating the trial decided to change the primary aim: to show that long-acting cabotegravir was as effective as daily Truvada.
Scientists involved with the study are planning an investigation to understand why some people who took long-acting cabotegravir or daily Truvada became infected.
After its analysis, the DSMB recommended that all participants get the results and are offered injectable cabotegravir.
Side effects
According to NIAID, both long-acting cabotegravir and Truvada were “generally safe and well tolerated.” Most people (80%) who received long-acting cabotegravir reported temporary pain and tenderness at the injection site vs. 31% of people who received injections of placebo.
A trial in women
Another clinical trial called HTPN 084 has enrolled more than 3,000 HIV-negative heterosexual women. This trial began about a year after the previous study and will also investigate the safety and effectiveness of long-acting cabotegravir. Study HTPN 084 has recruited participants from East and Southern Africa. The DSMB has looked at the interim data and recommended that it continue.
For the future
Detailed results from study HTPN 083 will be released at a future scientific conference. Long-acting cabotegravir for the prevention of HIV infection will likely be approved in Canada and other high-income countries and regions sometime over the next two years.
Viiv is developing plans to facilitate access to long-acting cabotegravir in low- and middle-income countries. However, it will probably be several years before those plans are implemented.
The results from HTPN 083 mark a major milestone in the HIV pandemic. The eventual regulatory approval of long-acting cabotegravir will result in more options for HIV prevention. It will also spur pharmaceutical companies to develop even longer-acting formulations of PrEP.
–Sean R. Hosein
Resources
Oral pre-exposure prophylaxis (PrEP) – CATIE fact sheet
How does PrEP prevent HIV? – CATIE video
REFERENCES:
- NIAID. Long-acting injectable drug prevents HIV among men who have sex with men and transgender women. Press release. 18 May 2020.
- Cohen J. Long-acting drug acts like a short-term AIDS vaccine. Science. 22 May 2020.