What Is HIV Pre-Exposure Prophylaxis (PrEP)?

HIV pre-exposure prophylaxis (PrEP) is a preventive strategy in which the use of antiretroviral medication can reduce the risk of getting HIV by up to 99%. There are currently three approved prescription medications:

• Truvada (emtricitabine + tenofovir disoproxil fumarate) is a daily pill approved for those at risk for HIV through sex or injection drug use.
• Descovy (emtricitabine + tenofovir alafenamide) is a daily pill approved for sexually active men and transgender women at risk for HIV.
• Apretude (cabotegravir extended-release injectable suspension), which is approved for at-risk adults and teens, is an injectable given every two months.

PrEP is not intended for everyone but is rather used in people who are at high risk of HIV infection. This includes serodiscordant couples in which one partner is HIV-positive and the other is HIV-negative.

Taking PrEP does not mean you can stop using condoms or avoid traditional risk-reduction strategies. The drugs used for PrEP do not prevent other sexually transmitted or blood-borne infections, including hepatitis C.

Truvada was the first drug approved for PrEP in 2012. Descovy (which includes an "improved" version of tenofovir that may be less impactful on the kidneys) was approved in October 2019 for cisgender men and transgender women. The first injectable form of PrEP, Apretude, was approved in December 2021.

Uses

PrEP is used in people who are more likely to be diagnosed with HIV as well as anyone in whom the preventive therapy may be considered beneficial.

According to guidance from the U.S. Preventive Services Task Force (USPSTF), PrEP is recommended for the following groups:

Because the dosing for PrEP is fixed and cannot be modified, people weighing less than 77 pounds would need to use other traditional preventive strategies.

Although people at low risk of infection can benefit from PrEP, there are risks associated with treatment (see "Side Effects" below) as well as potential costs. For these individuals, condoms and other traditional preventive strategies may be a more practical solution.

Before Taking

Prior to starting PrEP, your healthcare provider will need to confirm that you do not have HIV. This requires a simple blood test, either in the form of a rapid HIV test (which can return results in around 20 minutes) or a standard point-of-care test (which usually returns results in a couple of days).

In addition, the healthcare provider will order blood tests to check your kidney function or liver function. Because Truvada and Descovy can impair kidney function in some people, testing provides a baseline reading by which to monitor for any adverse effects. Although rare, Apretude may cause damage to the liver, and its use should be monitored as well.

You may also be screened for sexually transmitted infections, including hepatitis B. A pregnancy test is also recommended if you are in your child-bearing years.

Precautions and Considerations

PrEP should be delayed in anyone who has signs of a recent HIV infection. This is because HIV tests are designed to detect antibodies, which can take up to a month to develop after exposure to the virus. During this so-called "window period," an HIV test can return a false-negative result, meaning that you have HIV even if the test says otherwise.

Symptoms of acute HIV infection (also known as acute retroviral syndrome) are often flu-like and include:

• Fever
• Headache
• Fatigue
• Swollen lymph nodes
• Rash
• Sore joints or muscles
• Sore throat

You should also delay PrEP if you've had a possible exposure to HIV within the past month, either through unprotected sex, sex with a partner of unknown status, or shared needles.

Dosage

When used for PrEP, the recommended dose of Truvada and Descovy is one tablet daily taken with or without meals. The tablet must be taken every day to achieve optimal protection.

It can take up to three weeks for the drug to reach the maximum protective concentration. According to the Centers for Disease Control and Prevention (CDC), this can vary by the mode of transmission:

• Anal sex: 7 days of uninterrupted use
• Vaginal sex: 21 days of uninterrupted use
• Injecting drug use: 21 days of uninterrupted use

Apretude is administered first as two initiation injections given one month apart, and then every other month thereafter. Each injection is 600 mg.

Modifications

In 2018, the International Antiviral Society USA further endorsed the use of PrEP "on demand" for MSM only. This is a strategy not endorsed by the CDC but one that has gained the approval of many public health authorities concerned about the continued high infection rate in gay and bisexual men.

PrEP on demand is supported by research published in the New England Journal of Medicine, which showed that high-risk MSM (defined as having unprotected anal sex with at least two partners during the past two months) were 84% less likely to get HIV if they took oral PrEP before and after sex.

Follow-Up Testing

If you decide to pursue oral PrEP as a preventive strategy, you will be given a three-month prescription of Truvada or Descovy. Every three to six months thereafter you will need to undergo follow-up testing and evaluations per CDC guidance:

• Every three months: Repeat HIV testing, pregnancy testing, and STD testing for people with symptoms of an STD
• Every six months: Repeat creatinine clearance testing
• Every 12 months: Evaluate whether oral PrEP should continue based on self-reported adherence, individual risk assessment, treatment tolerance, and other factors

If you choose to receive injectable PrEP, HIV testing should be repeated before each injection and whenever any other STIs are diagnosed. Apretude comes with a boxed warning to not use the medication unless a negative HIV test is confirmed. This is to reduce the risk of developing drug resistance.

How to Take and Store

Truvada and Descovy can be taken with or without food but should not be split, crushed, or chewed as this can affect the absorption of the drug.

Truvada and Descovy can be stored safely at room temperature, ideally around 77 degrees F (25 degrees C). Keep the pills in their original light-resistant container. Do not remove the moisture-retardant sachet, and never store the pills on a sunny windowsill or in your glove compartment. Discard any expired tablets.

If you miss a dose, take it as soon as you remember. If it is near the time of your next dose, skip the original dose and continue as normal. Do not double up doses.

Apretude is injected into the gluteal muscles (buttocks) every two months by a healthcare provider. It can be given up to seven days before or after the date of the next scheduled injection.

Side Effects

As with all drugs, Truvada, Descovy, and Apretude can cause side effects. For the most part, they will be mild and transient and usually resolve within a week or so as your body adapts to treatment. In rare cases, the drugs can cause severe side effects, often in people with pre-existing health conditions.

Common

Truvada and Descovy have slightly different mechanisms of action but many of the same side effects. Because Descovy delivers tenofovir at a significantly lower dose, the incidence of side effects is lower (between 2% and 5%) compared to Truvada (between 5% and 9%).

The most common side effects of oral PrEP by order of frequency include:

The most common side effects of Apretude include:

• Injection site reactions
• Diarrhea
• Fever
• Headache
• Insomnia
• Fatigue

Severe

Severe side effects are rare but can occur. When taking oral PrEP (Descovy or Truvada) the most concerning is the risk of kidney impairment. This typically affects people with pre-existing kidney disease but can also occur in those who take medications actively excreted by the kidneys (see "Drug Interactions" below).

On rare occasions, this can lead to acute kidney failure, the symptoms of which include:

• Fatigue
• Loss of appetite
• Nausea or vomiting
• Muscle weakness
• Irregular or rapid heartbeat
• Confusion

In most cases, kidney function will return to baseline levels once treatment is stopped.

Apretude carries warnings about serious or severe hypersensitivity reactions, hepatotoxicity (liver damage), and depressive disorders. That said, your healthcare provider may want to monitor your liver function. Those who experience depressive symptoms or a hypersensitivity reaction should seek prompt medical attention.

Symptoms of a hypersensitivity reaction include:

• Rash
• Fever
• Blisters
• Facial swelling
• Swelling of the eyes, lips, tongue, or mouth
• Difficulty breathing

Warnings and Interactions

Both Truvada and Descovy carry a black box warning advising consumers that a severe flare-up of liver symptoms can occur in people with hepatitis B following the discontinuation of treatment. Black box warnings are the highest level of advisement from the Food and Drug Administration (FDA).

Although not contraindicated for use, Truvada and Descovy should be used with extreme caution in anyone with hepatitis B. If used, liver function tests should be routinely repeated. Hepatitis B treatment should also be considered.

Truvada and Descovy are considered safe for use during pregnancy. Both animal studies and human surveillance data have shown no increase in the risk of fetal harm compared to the general population. Breastfeeding is also presumed to be safe.

However, due to a lack of studies, it is unclear if Apretude is safe to take while pregnant or breastfeeding.

With that said, due to a lack of long-term safety research, it is important to speak with your healthcare provider about the benefits and risks of PrEP if you are pregnant, planning to get pregnant, or breastfeeding.

Drug Interactions

There are few major drug interactions associated with PrEP medication. The biggest concern with taking Truvada or Descovy is the risk of kidney-related side effects when taken with other drugs that also rely on the kidneys for excretion.

These include the following classes of drugs:

• Aminoglycoside antibiotics like Gentak (gentamicin), Tobrex (tobramycin), and streptomycin
• Antiviral drugs like Cytovene (ganciclovir), Valcyte (valganciclovir), Valtrex (valacyclovir), Vistide (cidofovir), and Zovirax (acyclovir)
• High-dose nonsteroidal anti-inflammatory drugs (NSAIDs) like Advil (ibuprofen), Aleve (naproxen), Celebrex (celecoxib), and Voltaren (diclofenac)

A dose adjustment or change of treatment may be needed if there is evidence of kidney impairment.

When taking Apretude, it's best to avoid certain medications, as they can cause significantly decreased blood levels of Apretude. This can reduce the effectiveness PrEP.

These medications include:

• Anticonvulsants like Tegretol (carbamazepine), Trileptal (oxcarbazepine), phenobarbital, and Dilantin (phenytoin)
• Antimycobacterial drugs such as rifampin, rifapentine, and rifabutin