In this episode, Rachel Cole, PharmD, explores the evolving landscape of medications for HIV pre-exposure prophylaxis (PrEP), spotlighting lenacapavir (Yeztugo)—a newly approved long-acting injectable option given just twice yearly.
She walks through how it compares to oral therapies like Truvada and Descovy, plus other injectables such as cabotegravir. Rachel also offers practical guidance on identifying candidates for HIV PrEP, navigating lab requirements, and managing side effects.
You’ll also hear strategies to help patients overcome cost barriers, improve adherence, and understand the importance of regular follow-up.
Whether you’re supporting patients at the pharmacy counter or staying current on HIV prevention, this episode delivers timely insights for pharmacy teams and other healthcare professionals.
This is an excerpt from our September 2025 Pharmacy Essential Updates continuing education webinar series.
CE Information:
TRC Healthcare offers CE credit for this podcast for pharmacist subscribers at our platinum level or higher and pharmacy technician subscribers. Log in to your Pharmacist’s Letter or Pharmacy Technician’s Letter account and look for the title of this podcast in the list of available CE courses. None of the speakers have anything to disclose.
Clinical Resources from Pharmacist’s Letter, Pharmacy Technician’s Letter, and Prescriber Insights:
- Article: Add Lenacapavir to Your List of PrEP Recommendations
- Checklist: HIV Pre-Exposure Prophylaxis (PrEP)
- New Drug Graphic: Lenacapavir (Yeztugo)
- Chart: Drug Interactions: Cytochrome P450 (CYP), P-glycoprotein, and More
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Transcript:
This transcript is automatically generated.
00:00:04 Narrator
Welcome to Clinical Capsules from TRC Healthcare, your go-to podcast for fast, evidence-based insights.
00:00:11 Narrator
On this episode, Clinical Pharmacist Rachel Cole explores the latest developments in HIV pre-exposure prophylaxis (PrEP)…
00:00:19 Narrator
with a spotlight on a new long-acting injectable option, lenacapavir, in an excerpt from our popular Pharmacy Essential Updates webinar series.
00:00:28 Narrator
TRC has been a trusted resource for healthcare professionals for over 40 years—and now we’re bringing that expertise straight to your ears every 2nd and 4th Tuesday, in bite-sized, actionable episodes…right here on Clinical Capsules.
00:00:43 Narrator
This podcast offers Continuing Education credit for pharmacists and pharmacy technicians.
00:00:48 Narrator
Please log in to your Pharmacist’s Letter or Pharmacy Technician’s Letter account and look for the title of this podcast in the list of available CE courses.
00:00:55 Narrator
None of the speakers have anything to disclose. Let’s dive in…
00:01:05 Rachel Cole
Our article gives us a quick overview of lenacapavir or Yeztugo, the first twice yearly subcutaneous injectable option for HIV PrEP.
00:01:14 Rachel Cole
So, let’s brush up on our PrEP options and see how lenacapavir fits in.
00:01:21 Rachel Cole
Over 36,000 people are diagnosed with HIV in the US each year, and with PrEP, the goal is to prevent HIV in high-risk patients by using antiretroviral meds long term to reduce their risk of developing HIV prior to exposure.
00:01:38 Rachel Cole
We can emphasize how effective PrEP can be when patients are adherent. Oral and injectable PrEP reduces risk of HIV through sex by about 99% when taken as prescribed.
0:01:51 Rachel Cole
Over the last several years, there’s been an uptick in patients using PrEP.
0:01:55 Rachel Cole
For instance, in 2022, about 36% of people who could benefit from PrEP were prescribed, and that’s up from about 23% in 2019.
0:02:05 Rachel Cole
But we still have an estimate of over 1,000,000 people who could benefit from PrEP in the US.
00:02:11 Rachel Cole
And additional resources are needed to address unmet needs to get more people on PrEP.
00:02:18 Rachel Cole
So let’s take a closer look at who’s eligible for PrEP and how we can help identify potential candidates.
00:02:24 Rachel Cole
And really, we should keep PrEP in mind in our discussions with all sexually active patients to help raise awareness and reduce stigma.
00:02:32 Rachel Cole
HIV can affect anyone, regardless of sexual orientation, race, ethnicity, gender or age.
00:02:39 Rachel Cole
And some examples of how we can do this in the pharmacy are watching for patients who report risk factors… maybe getting prescriptions for sexually transmitted infections or patients who may be purchasing syringes or naloxone regularly
00:02:53 Rachel Cole
or generally promoting that your pharmacy provides PrEP, just like how we let all of our patients know, we offer immunizations or other patient care services.
00:03:03 Rachel Cole
Think of PrEP as another harm reduction service we can offer as pharmacists.
00:03:08 Rachel Cole
And getting into the habit of discussing PrEP is key, since some patients may feel worried or embarrassed to ask about it. So, this gives people an in to have further conversations.
00:03:21 Rachel Cole
Plus, people at risk of HIV are often under recognized or may not report that they’re participating in high-risk behaviors or know their behaviors are risky…
00:03:31 Rachel Cole
Such as having unprotected sex with multiple partners, people who inject drugs, especially if they share needles, or those who’ve had a recent sexually transmitted infection, such as gonorrhea or chlamydia, during the past six months.
00:03:45 Rachel Cole
Since this shows they’ve had recent sexual activity that could result in HIV exposure.
00:03:50 Rachel Cole
These are some groups who are particularly vulnerable to acquiring HIV and are likely to benefit from PrEP.
00:03:59 Rachel Cole
So be ready to recommend or provide PrEP for these patients at increased risk as well as any other patient who requests it, even if they don’t report at risk behavior.
00:04:09 Rachel Cole
Again, realizing that not all patients will openly share information about their behaviors.
00:04:16 Rachel Cole
But before starting PrEP, there are a few key things to verify, and one of the biggest ones is making sure that the patient is HIV negative.
00:04:25 Rachel Cole
Since using PrEP in an HIV positive patient is linked to developing drug resistant HIV, so document a negative HIV test before initiating therapy.
00:04:36 Rachel Cole
Ideally with an antigen and a body blood test, we want to stay away from rapid tests that only check for antibodies, including those that use oral fluid because they are less sensitive for the detection of acute or recent infection than blood tests.
00:04:52 Rachel Cole
Also ask about signs and symptoms of acute HIV infection such as fever or night sweats, since there is a window period, or a time between HIV exposure, and when a test can detect HIV in your body.
00:05:05 Rachel Cole
Patients will also need other labs, such as tests for hepatitis or kidney function.
00:05:12 Rachel Cole
So now let’s talk about the medications that can be used to prevent HIV in these patients, including another recently approved injectable option and some of the things to consider when determining which product may be most appropriate.
00:05:26 Rachel Cole
There are currently two oral and two injectable options for PrEP that are approved for adults and adolescents weighing at least 35 kg or 77 lbs.
00:05:37 Rachel Cole
So, let’s see how the oral meds stack up, both Truvada and Descovy each contain 200 milligrams of emtricitabine, but their tenofovir component is different.
00:05:48 Rachel Cole
Truvada contains 300 milligrams of tenofovir disoproxil fumarate, while Descovy contains 25 milligrams of tenofovir alafenamide.
00:05:59 Rachel Cole
Both of these are once daily meds, and both of these will need kidney function monitoring with different creatinine clearance, cut offs for use.
00:06:07 Rachel Cole
Both May also rarely decrease kidney function, but Descovy seems to have less of an impact than Truvada.
00:06:14 Rachel Cole
A few other differences, Truvada decreases bone density, but doesn’t seem to impact fractures where Descovy may cause weight gain and increased triglycerides.
00:06:25 Rachel Cole
And then we have injectable cabotegravir, which contains 600 milligrams of extended release cabotegravir.
00:06:32 Rachel Cole
It’s administered by a healthcare provider into the gluteus or buttock via an intramuscular injection once a month for two months and then every two months thereafter.
00:06:43 Rachel Cole
So, this is a long-acting option. Where the orals are daily options.
00:06:48 Rachel Cole
Also, with cabotegravir regular monitoring of kidney function is not needed like it is with the orals, so cabotegravir may be an option for patients with significant kidney disease.
00:06:59 Rachel Cole
And cabotegravir also does not seem to impact weight, cholesterol, or bone density.
00:07:06 Rachel Cole
And then we have the recently approved injectable lenacapavir, which contains 463.5 milligrams per 1.5 milliliter injection of extended release lenacapavir.
00:07:20 Rachel Cole
It’s administered by a healthcare provider into the abdomen or thigh via subcutaneous injections twice yearly or every six months or every 26 weeks.
00:07:31 Rachel Cole
So this is another long-acting option. Also like cabotegravir regular monitoring of kidney function is not needed, like it is with the orals.
00:07:41 Rachel Cole
So lenacapavir may be another option for patients with significant kidney disease.
00:07:47 Rachel Cole
Patients should get two subcutaneous or 927 milligrams total of lenacapavir on Day 1 + two 300 milligram lenacapavir oral tablets daily on days one and two.
00:08:02 Rachel Cole
Followed by 927 milligrams subcutaneously every six months.
00:08:08 Rachel Cole
The initial and subsequent injections must be administered by a healthcare professional, and we should ensure the scheduled injections occur within 26 weeks, ±14 days of the patient’s last injection.
00:08:22 Rachel Cole
We can bridge with 300 milligrams of oral lenacapavir once weekly if there is a delay of more than 14 days.
00:08:30 Rachel Cole
But keep in mind that reinitiation with the injection tablet combo is required if there’s a delay of more than 14 days without the oral bridge.
00:08:41 Rachel Cole
There are many factors to consider when evaluating PrEP options, we’ve touched on how they are all highly effective if taken as prescribed and then kidney function.
00:08:51 Rachel Cole
But we also want to consider the patient population we’re treating and if patients are pregnant or breastfeeding. Cost may also play a role.
00:09:00 Rachel Cole
As well as interactions may impact which option we recommend.
00:09:05 Rachel Cole
Then we use shared decision making with PrEP candidates to identify a regimen that will work best for them.
00:09:12 Rachel Cole
So let’s review some other med considerations. Truvada and Apretude are recommended PrEP options regardless of high-risk behaviors.
00:09:21 Rachel Cole
Descovy is only approved as PrEP for men and transgender women who have sex with men.
00:09:25 Rachel Cole
We can go ahead and suggest Truvada first for most patients, since it’s effective, can be used regardless of high-risk behavior, and it’s the least expensive option.
00:09:35 Rachel Cole
It also has the most evidence for use during pregnancy and breastfeeding, and for people who inject drugs.
00:09:42 Rachel Cole
We can think of Descovy instead of PrEP for patients with osteoporosis or moderate kidney impairment, since it’s less likely to decrease bone mineral density or kidney function compared to Truvada.
00:09:54 Rachel Cole
We can consider long acting injectable, cabotegravir or lenacapavir for patients who have severe kidney impairment, have difficulty adhering to oral PrEP, or prefer getting an injection every two or every six months over taking a daily pill.
00:10:12 Rachel Cole
And regardless of which med is used for PrEP, we, as pharmacists and techs play a key role in helping ensure therapy is safe.
00:10:20 Rachel Cole
One way we can do this is by making sure med profiles are updated and watching for drug interactions.
00:10:26 Rachel Cole
For example, tenofovir disoproxil fumarate in Truvada interacts with some hep C meds such as Epclusa and Harvoni, leading to increased tenofovir levels, and the potential for increased kidney injury and other side effects.
00:10:42 Rachel Cole
Cabotegravir or the tenofovir alafenamide in Descovy interact with certain meds such as phenytoin or rifampin.
00:10:52 Rachel Cole
These meds can significantly decrease cabotegravir concentrations. If patients need to stay on these medications, usually recommend Truvada instead. Also advise patients on cabotegravir or Descovy to avoid St. John’s Wort.
00:11:08 Rachel Cole
Now our newest PrEP option, lenacapavir, or Yeztugo, is a substrate of CYP3A and P glycoprotein or PGP and moderately inhibits CYP3A and PGP.
00:11:22 Rachel Cole
Consider another PrEP option for patients already on the strong inducer such as carbamazepine or phenobarbital, and be mindful that if a patient already on lenacapavir starts a strong or moderate inducer, supplemental, oral and or injectable PrEP doses may be needed.
00:11:41 Rachel Cole
Lenacapavir is administered subcutaneously into the abdomen or thigh, and since it takes 2 injections to administer, the full dose, make sure that second injection site is at least 4 inches from the 1st and at least two inches from the navel.
00:11:57 Rachel Cole
Lenacapavir for PrEP can be stored at room temperature and keep the vials in the original carton to protect from light.
00:12:05 Rachel Cole
To help manage any discomfort from the injections, cold packs can be applied to the sites before and after injection, or use an oral analgesic if clinically appropriate.
00:12:15 Rachel Cole
And keep in mind a drug depot collects under the skin at the sites, so it’s common for patients to feel a bump or a nodule just under the skin.
00:12:26 Rachel Cole
Overall, all four PrEP regimens are well tolerated, and we can emphasize this and help set patients up for success.
00:12:34 Rachel Cole
With the two oral meds, caution patients about a start-up syndrome, which includes a headache, nausea, diarrhea and improves with time. Usually it lasts less than a month.
00:12:45 Rachel Cole
Educate that GI upset usually lasts less than a month and to take it with food to limit initial nausea.
00:12:53 Rachel Cole
We don’t see this start up syndrome with cabotegravir or lenacapavir. The main concern with the injectable options is injection site reactions, which includes pain, tenderness, local swelling.
00:13:05 Rachel Cole
And these are usually manageable and temporary.
00:13:09 Rachel Cole
We can also help breakdown cost barriers so that price doesn’t get in the way of HIV prevention.
00:13:16 Rachel Cole
Point out that most patients can get PrEP with no co-pay under the Affordable Care Act, and manufacturers often have med assistant programs.
00:13:25 Rachel Cole
Also check for state programs. And there are multiple patient assistant programs found on HIV.gov.
00:13:33 Rachel Cole
In addition to counseling on what side effects to expect and how they’re usually temporary and helping patients afford their PrEP, there are other ways we can also encourage med adherence.
00:13:45 Rachel Cole
Recommend technology, such as using smartphone apps, or help set up refill reminders or offer prescription delivery.
00:13:53 Rachel Cole
We should also take the opportunity to emphasize other safe practices, including condoms, and remind patients PrEP only protects against HIV, not other sexually transmitted infections.
00:14:05 Rachel Cole
We can also remind patients to follow up at least every three months for oral PrEP and for cabotegravir advise follow up one month after the initial injection for the second injection, and then recommend follow up every two months for cabotegravir.
00:14:20 Rachel Cole
Patients on the lenacapavir injection for PrEP should follow-up every six months for their injections and HIV screening.
00:14:27 Rachel Cole
But follow-up can be more frequent and as needed. In addition to check-ins via text or calls in between in person visits.
00:14:35 Rachel Cole
Follow-up is important for many reasons, including repeat HIV testing, refilling prescriptions and screening for other STI’s.
00:14:45 Rachel Cole
Check out our online resources, our new drug graphic for lenacapavir or Yeztugo for PrEP and the updated HIV pre-exposure prophylaxis checklist for more details on all HIV PrEP options.
00:15:01 Narrator
We hope you enjoyed and gained practical insights from listening to this episode!
00:15:06 Narrator
Now that you’ve listened, pharmacists and pharmacy technicians can receive CE credit.
00:15:11 Narrator
Just log into your Pharmacist’s Letter or Pharmacy Technician’s Letter account and look for the title of this podcast in the list of available CE courses.
00:15:19 Narrator
We’ve linked the resources we mentioned—and more on today’s topic—right in the show notes.
00:15:24 Narrator
Those links will take you straight to our websites, where you’ll find even more concise, evidence-based charts, articles, and tools.
00:15:33 Narrator
If you’re not yet a subscriber, now’s the time—sign up today to stay ahead with trusted, unbiased insights, and continuing education.
00:15:41 Narrator
And as a listener, you can save 10% off on a new or upgraded subscription with code cc1025 at checkout.
00:15:51 Narrator
Also, be sure to explore our other TRC content—podcasts like Medication Talk and Rumor vs Truth, plus our full Pharmacy Essential Updates webinar series for deeper dives.
00:16:02 Narrator
Thanks for listening… stay sharp, stay current—and we’ll catch you next time on Clinical Capsules!
Clinical Capsules
