- Human immunodeficiency virus (HIV) infection remains an ongoing problem and a key public health interest.
- Experts are interested in finding the best strategies for HIV prevention, including the best options for pre-exposure prophylaxis.
- One study revealed that injection of the medication lenacapavir every six months could greatly reduce the risk for HIV infection among at-risk individuals.
Human immunodeficiency virus (HIV) affects a person’s immune system. People with HIV can take medication to prevent it from progressing to acquired immunodeficiency syndrome (AIDS).
However, HIV currently has no cure. Thus, prevention strategies are essential to HIV-related research. Pre-exposure prophylaxis (PrEP) involves taking medication to prevent HIV.
A study recently published in the New England Journal of Medicine evaluated using lenacapavir, an antiretroviral drug typically used to treat HIV infections, as a PrEP strategy.
Researchers also found this option to be more effective than the PrEP option of taking emtricitabine–tenofovir disoproxil fumarate (Truvada) daily.
The use of lenacapavir could greatly improve the options for PrEP in at-risk populations.
This study was a phase 3, double-blind, randomized, multicenter, active-controlled trial. The researchers were testing the efficacy of subcutaneous injections of lenacapavir in preventing HIV infection.
The research involved a diverse sample that encompassed many groups that are often impacted by HIV infection. Researchers specifically sought to include participants who have not often been part of HIV clinical trials.
Participants were individuals who had “condomless receptive anal sex with partners assigned male at birth.” Researchers included cisgender men and participants who identified as transgender and gender nonbinary.
All potential participants initially had unknown HIV status but underwent HIV testing. Participants included in PrEP treatment were HIV-negative.
The trial included 3,265 participants that researchers randomized into two groups. One group received a daily oral medication called emtricitabine-tenofovir disoproxil fumarate (F/TDF), known under the trade name Truvada, and a placebo injection every 6 months.
The other group received the lenacapavir injection every 6 months and a daily oral placebo. The lenacapavir group also received 2 initial oral loading doses of lenacapavir. Participants underwent regular testing for HIV infection.
In addition to this medication comparison, researchers also looked at wider data from the initially screened population to look at the background incidence of HIV infection.
The study found that lenacapavir injections were the most effective option for HIV prevention. In the group of over 2,100 participants receiving lenacapavir, only two participants contracted HIV, compared to nine participants in the F/TDF group.
The outcome for the lenacapavir was also far better than the background incidence estimate.
Overall, adherence to lenacapavir was much higher than adherence to F/TDF. Researchers note that there was evidence that participants in the F/TDF group who acquired HIV had “low or no adherence or had discontinued F/TDF” over a week and a half before receiving their HIV diagnoses.
Study author Moupali Das, MD, MPH, Vice President of Clinical Development, HIV Prevention and Pediatrics at Gilead Sciences, highlighted the following components of the study’s findings to Medical News Today:
“There were only two incident cases of HIV infection among 2,179 trial participants who received injections of twice-yearly lenacapavir. This corresponds to 99.9% of participants receiving lenacapavir for pre-exposure prophylaxis (PrEP) in the trial not acquiring HIV – translating to a 96% risk reduction compared to the estimated background HIV incidence rate among the study population. Additionally, twice-yearly lenacapavir was 89% more effective than once-daily Truvada.”
This research does have some limiting components to consider. During the trial, the Food and Drug Administration (FDA) placed about a 5-month hold on lenacapavir injections. Thus, some participants could not receive their originally assigned regimen during this timeframe.
At first, participants due for their injections during this time instead received F/TDF or emtricitabine–tenofovir alafenamide fumarate (F/TAF). After a little more than a month of the hold, participants in the lenacapavir group were able to receive weekly oral lenacapavir until the FDA lifted the injection hold. This could have affected the study’s outcomes.
Second, researchers had certain inclusion criteria that affected the sample. There was also some incidence of ineligible participants still undergoing randomization screening and randomization, which could have affected the results.
Additionally, some participants who were eligible for randomization were not randomized. The adherence to injections was higher than adherence to daily oral medication, and this should also be taken into consideration.
When researchers estimated the background incidence of HIV infection, they only used a cross-sectional incidence cohort. Researchers did not do long-term follow-up regarding this data point. They also acknowledge that the approach they used could have led to an underestimation of the incidence of HIV infection.
Overall, the study did not identify any safety concerns with lenacapavir use. However, researchers acknowledge it is likely that the two participants in the lenacapavir group who contracted HIV developed a certain resistance from the sole use of lenacapavir. This may need to be addressed in future research.
Das noted that:
“There are additional, non-pivotal PURPOSE trials studying twice-yearly lenacapavir for PrEP in additional populations and geographies. These studies are underway. Additionally, participants in the PURPOSE 2 trial – as well as the PURPOSE 1 trial, studying twice-yearly lenacapavir for PrEP among cisgender women – are being or have been offered open-label lenacapavir, and we will continue to monitor individuals receiving lenacapavir injections.”
The current study was funded by Gilead Sciences, which produce lenacapavir.
This research presents an effective option for preventing HIV infection in at-risk individuals. Researchers note that current approval of lenacapavir use is limited to certain people who have multidrug-resistant HIV, so greater approval will be required for more widespread use.
There may also be additional barriers to its use. Charles Flexner, MD, professor of clinical pharmacology and infectious disease with John Hopkins School of Medicine and principal investigator of the Long-Acting and Extended-Release Antiretroviral Research Resource Program (LEAP), who was not involved in the current study but whose research has also received funding from Gilead, explained to MNT that “the biggest question surrounding long-acting injectable PrEP is access and affordability.”
“While these drugs are likely to be accessible in high-income countries, the latest estimates suggest it may take years for generic or low-cost versions to become available in low- and middle-income countries, where most of the world’s new HIV infections are occurring,” he noted.
However, Flexner added, “the effectiveness of twice-yearly lenacapavir is approaching that of a vaccine at preventing an infection that may never have an effective vaccine.”
James Cole, Senior Policy, Research and Influencing Manager at the National AIDS Trust in the United Kingdom emphasized the clinical implications of the trial’s results to MNT. He told us that:
“The results of the PURPOSE 2 study demonstrate that twice-yearly lenacapavir is a transformative option for HIV prevention among cisgender men and transgender communities. With a 96% reduction in HIV incidence compared to the background rate, Lenacapavir is not just effective, but also innovative and discreet, helping to address significant barriers for underserved communities who often face stigma and challenges adhering to daily oral regimens. This underscores the importance of integrating Lenacapavir into our HIV prevention strategies, particularly as the U.K. and the international community works towards UNAIDS’ 2030 targets.”
