HIV pre-exposure prophylaxis (PrEP) is a preventive strategy in which the daily use of the antiretroviral drug Truvada (emtricitabine + tenofovir disoproxil fumarate) or Descovy (emtricitabine + tenofovir alafenamide) can reduce the risk of getting HIV by up to 99%.
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.
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. PrEP requires a commitment to daily pill-taking and routine blood tests for the strategy to work.
Truvada is approved use in PrEP in both cisgender men and women as well as transgender men and women. By contrast, Descovy is only approved for cisgender men and transgender women due to the lack of cisgender women and transgender men in clinical trials. Studies are currently underway to evaluate Descovy for PrEP in people who engage in receptive vaginal sex.
According to guidance from the U.S. Preventive Services Task Force (USPSTF), PrEP is recommended for the following groups:
|Risk Group||Risk Category|
|Men who have sex with men (MSM)||Who are in a serodiscordant relationship|
|Who do not use condoms consistently for receptive or insertive anal sex|
|Who have had gonorrhea or syphilis within the past six months|
|Heterosexual women and men||Who are in a serodiscordant relationship|
|Who do not use condoms consistently with partners of unknown status or at high risk of having HIV (such as an injecting drug user)|
|Who have had gonorrhea or syphilis within the past six months|
|Injecting drug users||Who have shared needles or other injecting drug paraphernalia (including spoons, cotton balls, or water)|
|Who are at risk of getting HIV from sex|
In addition, adolescents or adults considering PrEP must weigh at least 77 pounds (35 kilograms) to be candidates for treatment.
Because the dose of Truvada and Descovy 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.
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. Because Truvada and Descovy can impair kidney function in some people, the test provides a baseline reading by which to monitor for any adverse effects.
Truvada and Descovy should not be used in anyone with a creatinine clearance of less than 30 milliliters per minute (mL/min). Values under 30 mL/min are an indication of severe kidney impairment.
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:
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.
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
According to the CDC, PrEP reduces the risk of HIV from sexual contact by 99% if taken daily. Among injecting drug users, PrEP reduces the risk by at least 74%.
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 PrEP before and after sex.
How to Take PrEP On-Demand
The International Antiviral Society USA recommends PrEP on-demand on a “2-1-1” schedule, namely:
- Two tablets of Truvada are taken two to 24 hours before sex.
- One tablet is taken 24 hours after the first dose.
- A final tablet is taken 24 hours later.
If the partners engage in sex before the end of the 48-hour period, they should continue to take PrEP every 24 hours until 48 hours after their last sexual episode.
If you decide to pursue 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 PrEP should continue based on self-reported adherence, individual risk assessment, treatment tolerance, and other factors
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.
As with all drugs, Truvada and Descovy 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.
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 by order of frequency include:
Rash (usually mild)
Severe side effects are rare but can occur. 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:
- Loss of appetite
- Nausea or vomiting
- Muscle weakness
- Irregular or rapid heartbeat
In most cases, kidney function will return to baseline levels once treatment is stopped.
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.
A 2016 study in PLoS Medicine reported that mothers on PrEP only transmit miniscule amounts of tenofovir and emtricitabine through breastmilk and that nine out of 10 have no detectable traces at all.
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.
There are few major drug interactions associated with either Truvada or Descovy. The biggest concern 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.
To avoid interactions, always advise your healthcare provider about any drugs you take, whether they are prescription, over-the-counter, herbal, nutritional, or recreational.
Centers for Disease Control and Prevention. How effective is PrEP? Updated November 3, 2020.
U.S. Food and Drug Administration. FDA In brief: FDA continues to encourage ongoing education about the benefits and risks associated with PrEP, including additional steps to help reduce the risk of getting HIV. July 1, 2019.
U.S. Food and Drug Administration. FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic. October 3, 2019.
Gilead Sciences. Gilead statement on commitment to advancing Descovy for PrEP™ Study in cisgender women & adolescent females. December 3, 2019
Gilead Sciences. Package insert – Descovy. Updated October 2019.
Centers for Disease Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States – 2017 update. Updated March 2018.
Delaney KP, Hanson DL, Masciotra S, Ethridge SF, Wesolowski L, Owen SM. Time until emergence of HIV test reactivity following infection with HIV-1: Implications for interpreting test results and retesting after exposure. Clin Infect Dis. 2017;64(1):53-9. doi:10.1093/cid/ciw666
Yerly S, Hirschel B. Diagnosing acute HIV infection. Exp Rev Anti-Infective Ther. 2012;10(1):31-41. doi:10.1586/eri.11.154
Saag MS, Benson CA, Gandhi RT, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society-USA panel. JAMA. 2018 Jul 24;320(4):379-96. doi:10.1001/jama.2018.8431
Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. 2015;373:2237-46. doi:10.1056/NEJMoa1506273
Gilead Sciences. Package insert – Truvada. Updated July 2012.
National Kidney Foundation. Acute kidney injury (AKI). Updated February 3, 2017.
Mugwanya KK, Hendrix CW, Mugo NR, et al. Pre-exposure prophylaxis use by breastfeeding HIV-uninfected women: A prospective short-term study of antiretroviral excretion in breast milk and infant absorption. PLoS Med. 2016 Sep 27;13(9):e1002132. doi:10.1371/journal.pmed.1002132
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