A drug used to treat HIV infections can also effectively prevent them, a new clinical trial demonstrates.
- 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.
Injections of
lenacapavir were over 96% effective at preventing HIV infection.
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.
Lenacapavir
for HIV prevention: Does it work?
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.”
Are
there any concerns about the study findings?
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.
Twice-yearly
lenacapavir could act like an HIV vaccine
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:
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