Pre-exposure prophylaxis, commonly known as PrEP, represents one of the most significant advances in HIV prevention in recent decades. When taken as prescribed, PrEP reduces the risk of getting HIV from sex by approximately 99% and from injection drug use by more than 74%. Despite its remarkable effectiveness, many people who could benefit from PrEP are not taking it. This comprehensive guide covers everything you need to know about PrEP — how it works, who should take it, the different formulations available, and how to access it.
What Is PrEP?
PrEP stands for pre-exposure prophylaxis. "Pre-exposure" means taking the medication before potential exposure to HIV, and "prophylaxis" means prevention. PrEP is a prescription medication taken by HIV-negative people to prevent HIV infection. It works by maintaining sufficient levels of antiretroviral drugs in the body so that if HIV enters the bloodstream, the drugs can prevent the virus from establishing a permanent infection.
The concept of PrEP was validated in the landmark iPrEx trial, published in the New England Journal of Medicine in 2010, which demonstrated that daily oral tenofovir/emtricitabine (TDF/FTC) reduced HIV acquisition by 44% overall and by 92% among participants with detectable drug levels. Subsequent studies confirmed even higher effectiveness with consistent adherence.
How Does PrEP Work?
PrEP works by using antiretroviral drugs — the same class of drugs used to treat HIV — to create a protective barrier in the body before HIV exposure occurs. The drugs in PrEP work by blocking the enzymes that HIV needs to replicate and establish infection in the body.
Specifically, the most commonly used PrEP medications contain drugs that inhibit reverse transcriptase (the enzyme HIV uses to convert its RNA into DNA) and integrase (the enzyme HIV uses to insert its DNA into the host cell's genome). By blocking these enzymes, PrEP prevents HIV from replicating and spreading throughout the body even if the virus enters the bloodstream.
For PrEP to be maximally effective, it is important to take it consistently as prescribed. Drug levels in rectal tissue reach protective levels within about 7 days of daily dosing, while drug levels in vaginal tissue may take up to 21 days to reach protective levels.
Who Should Consider PrEP?
PrEP is recommended for HIV-negative people who are at substantial risk of HIV infection. According to the CDC's PrEP guidelines, you should consider PrEP if you are HIV-negative and any of the following apply:
- You have had anal or vaginal sex in the past 6 months AND have a sexual partner with HIV (especially if the partner has an unknown or detectable viral load), have not consistently used condoms, or have been diagnosed with a sexually transmitted infection (STI) in the past 6 months
- You inject drugs AND have shared needles, syringes, or other drug injection equipment, or have been in a drug treatment program
- You have been prescribed PEP (post-exposure prophylaxis) and continue to engage in behaviors that put you at risk, or have used multiple courses of PEP
PrEP is appropriate for people of all genders, sexual orientations, and backgrounds. It is particularly important for gay and bisexual men, transgender women, Black and Hispanic/Latino individuals, and people who inject drugs — communities that are disproportionately affected by HIV in the United States.
Available PrEP Formulations
Several PrEP options are currently approved by the U.S. Food and Drug Administration (FDA):
1. Truvada (TDF/FTC) — Daily Oral PrEP
Truvada, a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), was the first PrEP medication approved by the FDA in 2012. It is taken as one pill daily and is approved for adults and adolescents weighing at least 35 kg. Generic versions are now available, significantly reducing the cost.
2. Descovy (TAF/FTC) — Daily Oral PrEP
Descovy, a combination of tenofovir alafenamide (TAF) and emtricitabine (FTC), was approved by the FDA in 2019. It has a similar efficacy profile to Truvada but may have a better safety profile for bone and kidney health. However, it is not currently approved for people at risk through receptive vaginal sex.
3. Apretude (Cabotegravir) — Long-Acting Injectable PrEP
Apretude (cabotegravir long-acting injectable) was approved by the FDA in December 2021 and represents a major advance in PrEP. Instead of a daily pill, Apretude is given as an injection every two months after two initial monthly injections. The HPTN 083 trial demonstrated that cabotegravir was 66% more effective than daily oral TDF/FTC in preventing HIV among cisgender men and transgender women who have sex with men.
How to Get PrEP
PrEP requires a prescription from a healthcare provider. Before starting PrEP, you will need:
- An HIV test to confirm you are HIV-negative
- Tests for kidney function (particularly important for Truvada/Descovy)
- Tests for hepatitis B and C
- STI screening
Follow-up appointments are typically scheduled every 3 months and include HIV testing, STI screening, and kidney function monitoring.
To find a PrEP provider near you, use the PrEP Locator or the HIV.gov PrEP resources page. Many health departments, community health centers, and Planned Parenthood locations offer PrEP services.
PrEP Cost and Insurance Coverage
The cost of PrEP can be a barrier for some people. However, several programs can help:
- Gilead's Advancing Access program — Provides Truvada and Descovy at no cost to uninsured patients who qualify
- ViiV Healthcare's Compass Initiative — Provides Apretude at no cost to eligible patients
- Ready, Set, PrEP — A federal program that provides free PrEP medications to uninsured Americans
- Medicaid and ACA marketplace plans — Required to cover PrEP with no cost-sharing under the Affordable Care Act
The HHS Ready, Set, PrEP program is a particularly valuable resource for those without insurance coverage.
PrEP Side Effects
PrEP is generally well-tolerated. The most common side effects of oral PrEP (Truvada/Descovy) are mild and typically resolve within the first few weeks of treatment. They may include nausea, headache, fatigue, and stomach pain. More serious but rare side effects include kidney problems (more common with Truvada) and bone density changes.
Cabotegravir injectable PrEP (Apretude) may cause injection site reactions, which are usually mild and temporary. It can also cause a hypersensitivity reaction in rare cases.
PrEP and STI Prevention
It is important to note that PrEP only prevents HIV — it does not protect against other sexually transmitted infections such as gonorrhea, chlamydia, syphilis, or herpes. Using condoms in addition to PrEP provides comprehensive protection against both HIV and other STIs.
Conclusion
PrEP is a powerful, evidence-based tool in the fight against HIV. With multiple formulations now available — including a long-acting injectable option — PrEP can fit into many different lifestyles and preferences. If you think PrEP might be right for you, talk to a healthcare provider or visit a PrEP clinic. Ending the HIV epidemic requires making prevention tools like PrEP accessible to everyone who needs them.