Joe’s Note: Here at tl;dr pharmacy, we’ve spent a lot of time covering human immunodeficiency virus (HIV) through the years. We have a 16 page, very inclusive cheat sheet that can be found here. We also have multiple posts regarding HIV which can be found here, here, here, and here. And in case that’s not enough, we also have posts discussing each specific HIV drug class which can be found here, here, here, here, and here.

See, I wasn’t lying. We really knocked HIV out of the park. However, there are two HIV topics that might have slipped through the cracks. Pre- and post-exposure prophylaxis (PEP). Today, we’re going to focus primarily on PEP. But fear not, a pre-exposure prophylaxis (PrEP) post is currently in the works.

Now we’re not going to dive super deep into pathophysiology and all that nerdy stuff regarding HIV. I will give you a pretty brief refresher, but if you want a more in-depth review, check out all of our previous posts that I have linked above. Alright let’s start.

Pathophysiology of HIV

As promised, I will only briefly review the pathophysiology of HIV. If you don’t already know, HIV is a retrovirus that targets and destroys CD4+ lymphocytes. Why is that a problem? Simply put, CD4+, also known as helper T cells, are like little tattletales. They don’t actually fight harmful substances (e.g., infections) in the body. Instead, they recognize harmful substances in the body and then communicate this message to real troops (e.g. B cells, CD8 T cells), who then go and fight these infections.

(Btw, if all of that seems like alphanumeric gibberish, it may also be helpful to check out this post on the basics of the immune system!)

So, if HIV is left untreated, it will destroy the CD4+ lymphocytes, causing severe immunosuppression, opportunistic infections, and death. Is there a cure for HIV? Unfortunately, there is not. Once you are diagnosed with HIV, you will forever have it. But thanks to rapidly developing science, HIV can be completely controlled, and patients can live very normal lives.

Treatment goals focus on suppressing the virus, thereby preventing further replication and spread throughout the body. This limits the degree of CD4+ cell destruction and avoids immunosuppression, opportunistic infections, and death.

So how can we suppress the HIV virus? That’s for the articles up top to teach you. But if you want a brief refresher, here are the seven steps of the HIV replication cycle. Inhibiting any of these steps will prevent virus replication and spread. And in case you are more of a visual learner, I added the HIV replication cycle picture that is engraved in all of our brains. Thanks, pharmacy school.

Binding: HIV attaches to a CD4 receptor on the surface of a host cell, typically a CD4 T lymphocyte
Fusion: The HIV virus merges with the host cell, releasing its genetic material (RNA) into the cell
Reverse Transcription: HIV’s reverse transcriptase enzyme converts the viral RNA into HIV DNA
Integration: The HIV DNA is inserted into the host cell’s genome using the integrase enzyme
Replication: The host cell’s machinery produces new HIV proteins and RNA molecule
Assembly: The viral proteins and RNA come together to form immature HIV virions
Budding: The immature virions are released from the host cell and mature into infectious HIV particles

Post-Exposure Prophylaxis (PEP) for HIV

You mean we can *prevent* HIV transmission? (Image)

Great. We reviewed HIV. But you know what’s even cooler than treating HIV? Preventing it in the first place in patients who were recently exposed. You might have a biased opinion and think that everyone who is exposed to HIV lives a high-risk life. That’s not always true.

You may be at risk of HIV exposure and not even know it. Sorry to be the bearer of bad news, but if you work in the healthcare setting, you most likely will be at a risk for an HIV exposure one way or another.

So now that I got you all nervous… How does HIV even spread from person to person? Generally through the exchange of bodily fluids that contain the virus, such as blood, sexual fluids, or breast milk. Let’s talk about the two types of HIV exposure: occupational and non-occupational. As the names clearly suggest:

Occupational HIV exposure: occurs in a healthcare setting, such as a hospital or clinic, where healthcare workers might be exposed to HIV-infected blood or body fluids during their duties
- Examples: needle-stick injuries, cuts from contaminated sharps, contact with mucous membranes or non-intact skin with potentially infectious body fluids
Non-Occupational HIV exposure: refers to exposure to HIV that occurs outside of a healthcare setting, such as during sexual contact, injection drug use, or other situations where there is a risk of exposure to HIV-infected blood or bodily fluids.
- Examples: unprotected sex with an HIV-positive partner, sharing needles for injecting drugs, or being sexually assaulted

God forbid, let’s say it’s the middle of influenza season and you picked up an extra shift at an immunization clinic to help make some extra money for Christmas shopping. We’re all human and are vulnerable to making mistakes. Let’s say you administer that vaccine to a patient. There is blood on that needle. Now, you go to cap the needle but accidentally poke your finger instead. And just like that, you are now at risk for occupational HIV exposure. So now what?

Criteria for Initiating HIV Post-Exposure Prophylaxis

As we’ve discussed, HIV is a life-altering condition and should not be taken lightly. So then, who should consider taking PEP?

Anyone who is HIV negative (or does not know their HIV status) and who in the last 72 hours:

May have been exposed to HIV during sex
Shared needles or other equipment to inject drugs
Were sexually assaulted
May have been exposed to HIV at work (occupation exposure)

As you can see we don’t have a lot of restrictions for starting PEP therapy. Really, there is just ONE restrictive criteria: PEP must be started within 72 hours (3 days) after a possible exposure. For all you visual learners, here is the treatment algorithm recommended by the CDC:

Okay let’s talk about it. I know how you may feel. If it’s me and it's been 75 hours since exposure, they BETTER give me some PEP because I don’t care about that 72 hour mark. Unfortunately, that 72 hour cutoff is backed up by literature. There are numerous studies that have shown that PEP will most likely not prevent HIV infection if started more than 72 hours after a person is exposed to HIV.

Dwight agrees…don’t wait to start PEP! (Image)

Much like other viruses, HIV generally establishes infection very quickly…often as fast as within 24 to 36 hours after exposure. That is why it’s very important that PEP be initiated as soon as possible. Every hour closer to the exposure reduces the risk of HIV transmission. The longer you wait, the less efficacious PEP will be.

Speaking of efficacy, how well does PEP actually work at preventing HIV transmission?

HIV PEP Efficacy

This is one of those common questions that you will receive as a pharmacist. “I am starting PEP, and I’m really scared. Please tell me that this will 100% prevent HIV transmission?” As much as we want to comfort that patient and tell them yes, we’d be lying.

Let’s review the literature. Surprisingly, there aren’t many studies on this topic. In fact, randomized studies of PEP have never been done. All the literature we have is observational.

The first evidence of PEP efficacy came from a case-control study in 1997, which showed an 81% reduction in the odds of HIV transmission among healthcare workers who were exposed to HIV. In 2016, the Centers for Disease and Prevention (CDC) reviewed six observational studies of PEP use by gay, bisexual, and other men who have sex with men. Of the 1535 men who took PEP, 1487 (96.9%) remained HIV negative, and 48 (3.1%) men acquired HIV.

A few years later, the CDC identified 15 new studies in other populations, including adults, adolescents, and children. These patients were exposed to HIV through consensual sex, sexual assault, injection drug use, or needlestick injuries. Of the 2209 people who took PEP, 2190 (99.1%) remained HIV negative, and 19 (0.9%) were diagnosed with HIV.

So as you can see, PEP is VERY effective in preventing HIV transmission when taken within 72 hours of exposure. That being said, it’s not 100% effective. There’s always a risk for treatment failure, and it’s important that we educate our patients (and ourselves) about this. A good counseling point could be:

“PEP can reduce the risk of getting HIV by more than 80%. The effectiveness is highly dependent on adherence. As long as PEP is used consistently and correctly as prescribed, efficacy is likely much higher than 80%.”

Before Initiating PEP Therapy

Alrighty, let’s say our patient meets the criteria, and the provider wants to initiate PEP therapy. What’s our next step? Per the CDC, a baseline assessment is required for individuals beginning PEP. This assessment should include the following:

HIV Rapid Test at Baseline:
- If positive: do NOT initiate PEP
- If negative: start PEP immediately
- If test is not available: start PEP immediately
Pregnancy Test:
- Perform on all patients who could become pregnant, are not using highly effective contraception, and have vaginal exposure to semen
- Purpose: some PEP medications may be harmful to a developing fetus, and it’s important to ensure that the patient is not pregnant prior to starting treatment
Serum Liver Enzyme Test:
- Purpose: Certain PEP therapy may be hepatotoxic, and adjustment is necessary in patients with altered liver function
Blood Urea Nitrogen (BUN)/Creatinine Test:
- Purpose: Certain PEP therapy may be nephrotoxic, and adjustment is necessary in patients with altered renal function
Sexually Transmitted Infection (STI) Screening:
- This is for patients being evaluated for PEP because of a sexual encounter. STI screening is generally NOT needed for occupational-exposures.
Hepatitis B, Hepatitis C Tests:
- Purpose: to allow for tailored treatment and preventing unnecessary or ineffective PEP

PEP Treatment Options

Screening looks great, and now it’s time to start PEP therapy. What are our options? Currently the CDC recommends two oral PEP regimens:

PEP therapy is only taken for a total of 28 days. As you can see, we have multiple different options. Which should we pick and when? Let’s talk about it.

What about Biktarvy?

Okay, so we went over the FDA-approved PEP regimens above. But there’s a new agent that’s making some noise in the PEP world: Biktarvy.

So at the time of this article (early 2025), Biktarvy is NOT FDA-approved for post-exposure prophylaxis. However, there are numerous studies that have proven its efficacy in preventing HIV transmission. Let’s review a few of them.

The first study was a prospective, single-arm, open-label, single-site trial that evaluated the safety, tolerability, and adherence to Biktarvy for prophylaxis following potential exposure to HIV. A total of 112 participants met the inclusion criteria for PEP and were included in this study. Primary results showed no HIV seroconversions through 24 weeks post exposure. In addition, most patients (96.4%) reported appropriate adherence to the 28-day PEP regimen. Lastly, adverse reactions attributed to Biktarvy were mild and included headache (n=2), diarrhea (n=2), and nausea (n=1). Overall, this study concluded that Biktarvy use for PEP was associated with strong efficacy, mild symptoms, and better adherence than the traditional PEP regimens.

If that’s not enough proof, here is another study that demonstrated the efficacy and safety for Biktarvy for PEP. This study was a non-randomized, single-site, open-label, single-arm trial that evaluated the safety, tolerability, and acceptability of Biktarvy for prophylaxis following potential non-occupational exposure to HIV-1. This study enrolled a total 52 HIV-negative participants. Most of the participants (90.4%) completed the 28-day Biktarvy course with no HIV seroconversions detected when tested at week 4 or at the 3-month interview. All adverse events were grade 1 and included nausea with or without vomiting (15.4%), fatigue (9.6%), and diarrhea (7.7%).

Sometimes it pays to think outside of the FDA-approved options box. (Image)

As you can tell, even though Biktarvy may not be FDA-approved for PEP use, it can still be a possible option. But why would we trial Biktarvy over the recommended options? Great question!

Our traditional PEP regimens consist of two separate medications that make up the traditional backbone: 2 NRTIs & 1 INSTI. Much like the recommended agents, Biktarvy is also made up of 2 NRTIs and one INSTI. Specifically it has Tenofovir alafenamide (NRTI), Emtricitabine (NRTI), and Bictegravir (INSTI).

However, unlike the traditional PEP regimens, Biktarvy has all 3 medications within ONE pill. Therefore, the main benefit of Biktarvy over the FDA-approved regimens is the reduced cost, pill burden, and increased adherence. Since studies have shown it to be just as efficacious with a similar side effect profile, why not use one pill and save some money? Exactly.

If Biktarvy is used for PEP therapy, the recommended dosing is as follows: one tablet (bictegravir 50 mg/emtricitabine 200mg/tenofovir alafenamide 25 mg) once daily for 28 days
- Altered Kidney Function:
  - CrCl ≥30 mL/min: no dosage adjustment necessary
  - CrCl <30 mL/min: use NOT recommended
- Altered Liver Function:
  - Mild to moderate impairment (Child-Pugh class A or B): no dosage adjustments necessary
  - Severe impairment (Child-Pugh class C): use is NOT recommended

The tl;dr of HIV PEP Therapy

If you’ve made it this far, congrats, you’re a rockstar! As a token of appreciation, here is a summary of everything we went over:

HIV is a life-alternating condition that destroys CD4+ lymphocytes causing severe immunosuppression, opportunistic infections, and death. The HIV replication cycle is composed of seven steps. Inhibition of any of these steps prevents HIV replication and spread throughout the body. These steps include:

Binding → Fusion → Reverse Transcription → Integration → Replication → Assembly → Budding

Post-exposure prophylaxis (PEP) can be classified as either:

Occupational HIV exposure: occurs in a healthcare setting, such as a hospital or clinic, where healthcare workers might be exposed to HIV-infected blood or body fluids during their duties
Non-Occupational HIV exposure: refers to exposure to HIV that occurs outside of a healthcare setting, such as during sexual contact, injection drug use, or other situations where there is a risk of exposure to HIV-infected blood or bodily fluids

HIV post-exposure prophylaxis (PEP) should be started in all patients who are HIV negative or unknown HIV status, and who in the last 72 hours:

May have been exposed to HIV during sex
Shared needles or other equipment to inject drugs
Were sexually assaulted
May have been exposed to HIV at work

PEP can reduce the risk of getting HIV by more than 80%. The effectiveness is highly dependent on rapid initiation of PEP from the incident and treatment adherence. As long as PEP is used as prescribed, efficacy is likely much higher than 80%.

The following baseline tests should be collected PRIOR to initiating PEP therapy:

HIV Rapid Test
Pregnancy Test
Serum Liver Enzyme Test
Blood Urea Nitrogen (BUN)/Creatinine Test
Sexually Transmitted Infection Screening
Hepatitis B Screening
Hepatitis C Screening

According to the CDC, the preferred PEP regimen includes:

Tenofovir disoproxil fumarate 300 mg/Emtricitabine 200 mg (Truvada) once daily PLUS Raltegravir (Isentress) 400 mg BID OR Dolutegravir (Tivicay) 50 mg once daily

An alternative PEP regimen includes:

Tenofovir disoproxil fumarate 300 mg/Emtricitabine 200 mg (Truvada) once daily PLUS Darunavir 800 mg PLUS Ritonavir 100 mg once daily

Dolutegravir is the preferred INSTI for pregnant patients. Dosing adjustment of Truvada is necessary for patients with a CrCl equal to 30-50 mL/min. Truvada use should be avoided in patients with a CrCl <30 mL/min.

Dolutegravir and darunavir use should be avoided in patients with severe hepatic impairment (Child-Pugh class C). Ritonavir must be given with darunavir and is primarily used for its CYP enzyme inhibition to allow for an increased serum concentration of darunavir.

PEP therapy MUST be taken as prescribed for a total of 28 days.

What Every Pharmacist Should Know about HIV Post-Exposure Prophylaxis (PEP)