Infection with the human immunodeficiency virus (HIV) is still a major public health concern. The best pre-exposure prophylactic options and other HIV prevention strategies are of interest to experts. According to one study, giving at-risk people an injection of lenacapavir every six months could significantly lower their risk of contracting HIV. The immune system is impacted by the human immunodeficiency virus, or HIV. To stop HIV from developing into acquired immunodeficiency syndrome (AIDS), people with the virus can take medication.

But there is currently no treatment for HIV. Prevention measures are therefore crucial to HIV-related research. To prevent HIV, pre-exposure prophylaxis, or PrEP, entails taking medication. Lenacapavir, an antiretroviral medication commonly used to treat HIV infections, was assessed as a PrEP strategy in a recent study that was published in the New England Journal of Medicine. Lenacapavir injections were more than 96% successful in preventing HIV infection. Additionally, researchers discovered that this option was more effective than the daily dose of emtricitabinetenofovir disoproxil fumarate (Truvada), which is the PrEP option. Lenacapavir use has the potential to significantly increase PrEP options for at-risk groups.

Lenacapavir for HIV prevention: Does it work?
This study was a multicenter, active-controlled, phase 3 double-blind randomized trial. The effectiveness of lenacapavir subcutaneous injections in preventing HIV infection was being investigated by the researchers. The study’s sample was broad and included a variety of groups that are frequently affected by HIV infection. Participants who have not frequently participated in HIV clinical trials were specifically targeted by the researchers. Participants were people who had receptive anal intercourse without condoms with partners who were assigned male at birth. Participants who identified as transgender and gender nonbinary were included in the study, along with cisgender men.

All possible participants were tested for HIV even though their status was initially unknown. HIV-negative individuals were included in PrEP treatment. Researchers randomly divided the 3,265 trial participants into two groups. One group was given emtricitabine-tenofovir disoproxil fumarate (F/TDF), marketed under the brand name Truvada, orally every day, along with a placebo injection every six months.

The other group was given a daily oral placebo and an injection of lenacapavir every six months. Two initial oral loading doses of lenacapavir were also given to the lenacapavir group. Regular HIV infection testing was performed on the participants. In addition to this comparison of medications, researchers examined the background incidence of HIV infection by examining broader data from the population that was first screened.

According to the study, lenacapavir injections were the best way to prevent HIV. Compared to nine participants in the F/TDF group, only two participants in the group of more than 2,100 receiving lenacapavir developed HIV. Lenacapavir’s results were also significantly better than the background incidence estimate. In general, lenacapavir adherence was significantly higher than F/TDF adherence. Researchers point out that there was proof that individuals in the F/TDF group who contracted HIV either stopped taking F/TDF more than a week and a half prior to being diagnosed with HIV, or had poor or no adherence.

Among the 2,179 trial participants who received twice-yearly injections of lenacapavir, there were only two incident cases of HIV infection. This translates to a 96 percent risk reduction in comparison to the estimated background HIV incidence rate among the study population, meaning that 99.9 percent of trial participants receiving lenacapavir for pre-exposure prophylaxis (PrEP) did not contract HIV. Furthermore, lenacapavir taken twice a year was 89% more effective than Truvada taken once daily.

Are there any concerns about the study findings?
There are certain limiting factors to take into account in this research. The Food and Drug Administration (FDA) halted lenacapavir injections for approximately five months during the trial. As a result, during this period, some participants were unable to receive their initially prescribed regimen. Initially, participants who were scheduled for injections during this period were given either emtricitabinetenofovir alafenamide fumarate (F/TAF) or F/TDF instead.

The FDA lifted the injection hold after a little over a month, allowing participants in the lenacapavir group to receive weekly oral lenacapavir. The results of the study might have been impacted by this. Second, the sample was impacted by the inclusion criteria that the researchers used. The results might have been impacted by the small number of ineligible participants who continued to go through randomization screening and randomization.

Furthermore, not all participants who qualified for randomization were randomized. It should also be noted that adherence to injections was higher than adherence to daily oral medication. Researchers only used a cross-sectional incidence cohort to estimate the background incidence of HIV infection. Regarding this data point, researchers did not conduct long-term follow-up. They also admit that their methodology might have resulted in an underestimation of the prevalence of HIV infection.

Overall, the study found no safety issues with the use of lenacapavir. Researchers do admit, though, that the two lenacapavir-using group members who got HIV most likely developed some sort of resistance as a result of using lenacapavir alone. Future studies may need to address this.

Two-yearly lenacapavir for PrEP is being studied in other populations and regions in non-pivotal PURPOSE trials. These investigations are in progress. Furthermore, open-label lenacapavir is being or has been offered to participants in the PURPOSE 1 and PURPOSE 2 trials, which are investigating twice-yearly lenacapavir for PrEP in cisgender women. We will also keep an eye on those who receive lenacapavir injections. Gilead Sciences, the company that makes lenacapavir, provided funding for the current study.

Twice-yearly lenacapavir could act like an HIV vaccine
This study offers a practical way to shield at-risk people from HIV infection. Because lenacapavir is currently only approved for use by specific individuals with multidrug-resistant HIV, researchers point out that more approval will be needed before it can be used more widely.

Its use might also be hampered by other factors. The main concern with long-acting injectable PrEP is access and affordability, according to Charles Flexner, MD, a professor of clinical pharmacology and infectious disease at John Hopkins School of Medicine and principal investigator of the Long-Acting and Extended-Release Antiretroviral Research Resource Program (LEAP). Although he was not involved in the current study, Gilead has funded his research.

According to recent estimates, it may take years for generic or affordable versions of these medications to become available in low- and middle-income countries, where the majority of new HIV infections worldwide are occurring, even though they are probably available in high-income countries, he said. But according to Flexner, lenacapavir, which is administered twice a year, is becoming as effective as a vaccine at preventing an infection for which there may never be a suitable vaccine.

Lenacapavir administered twice a year is a revolutionary option for HIV prevention among cisgender men and transgender communities, according to the findings of the PURPOSE 2 study. With a 96% decrease in HIV incidence when compared to the background rate, lenacapavir is not only efficient but also novel and covert, assisting in removing major obstacles for marginalized groups that frequently experience stigma and difficulties following daily oral regimens. This emphasizes how crucial it is to include lenacapavir in our HIV prevention plans, especially as the U.S. K. and the global community strives to meet the 2030 UNAIDS targets.

References:
https://www.medicalnewstoday.com/articles/lenacapavir-injection-lowers-hiv-risk-by-96#Twice-yearly-lenacapavir-could-act-like-an-HIV-vaccine
https://mygenericpharmacy.com/index.php/therapy,10