PrEP (HIV Pre-Exposure Prophylaxis)
Daily TDF/FTC & TAF/FTC, On-Demand 2-1-1, and Long-Acting Injectable Cabotegravir
Evidence grade 5 of 5, Settled. Read how the Atlas grades evidence.
The written rationale for this grade is still being prepared.
- FDA
- FDA Approved (oral PrEP 2012; injectable cabotegravir 2021)
Reference only. Not medical advice.
What can go wrong
PrEP does not protect against other STIs, and rising chlamydia, gonorrhea, and syphilis among some PrEP users reflects this gap rather than a drug effect. TDF/FTC can modestly reduce renal function and bone mineral density; TAF/FTC has a more favorable renal/bone profile but small weight and lipid differences. Acquiring HIV while on PrEP with incomplete adherence risks drug-resistant virus, which is why on-treatment HIV testing is mandatory. Injectable cabotegravir requires reliable follow-up because of its long tail. PrEP must be prescribed with baseline and periodic HIV testing to avoid inadvertently treating undiagnosed HIV with two drugs (which would risk resistance).
This is something to take to a clinician. The Atlas can tell you what is known about prep (hiv pre-exposure prophylaxis) in general. It cannot tell you what is happening in your body, and the difference matters most for exactly the symptoms that bring people to this page.
Pre-exposure prophylaxis (PrEP) is the use of antiretroviral medication by HIV-negative people to prevent acquisition. Oral PrEP with tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC, branded Truvada) was FDA-approved in 2012; tenofovir alafenamide plus emtricitabine (TAF/FTC, Descovy) followed. For men who have sex with men, on-demand dosing (the 2-1-1 schedule from the IPERGAY trial) is an evidence-based option. The major advance is long-acting injectable cabotegravir (Apretude), FDA-approved in 2021 after the HPTN 083 and HPTN 084 trials, given as an intramuscular injection every two months. Adherence is the key determinant of efficacy: when taken as prescribed, oral PrEP reduces sexual HIV acquisition by about 99 percent. Men's-health telehealth platforms have become a significant access channel for PrEP.
Taking HIV medication before exposure to prevent infection, now available as a pill or an every-two-months injection.
What people take it for
What it is taken for. Approval, where it exists, covers only some of these.
How it works
PrEP drugs are antiretrovirals that block HIV at the earliest steps of infection. Tenofovir and emtricitabine are nucleoside/nucleotide reverse transcriptase inhibitors that prevent the virus from establishing infection in exposed cells if drug is present at adequate mucosal concentrations. Cabotegravir is an integrase strand transfer inhibitor formulated as a long-acting injectable nanosuspension that maintains protective concentrations for roughly two months per dose. Because PrEP prevents establishment of infection, it must be present before and around the time of exposure; on-demand dosing front-loads two pills 2-24 hours before sex, then one pill at 24 and 48 hours after.
On-demand and injectable: who they are and are not for
The 2-1-1 on-demand regimen is validated for cisgender men who have sex with men; it is not recommended for vaginal exposure because tissue drug kinetics differ. Long-acting injectable cabotegravir removes daily-adherence dependence and was superior to daily oral TDF/FTC in HPTN 083 (MSM and transgender women) and HPTN 084 (cisgender women), but it carries its own caveats: a long pharmacologic tail means that if someone stops injections and acquires HIV, sub-therapeutic cabotegravir can select for integrase resistance, so rigorous HIV testing around each injection is essential.
What people get wrong
Often saidPrEP protects against all STIs
ActuallyPrEP only prevents HIV. It offers no protection against chlamydia, gonorrhea, syphilis, herpes, or HPV; combined prevention still requires condoms and STI screening.
Often saidYou can start and stop oral PrEP freely with no consequence
ActuallyProtection depends on adequate drug levels. Inconsistent dosing reduces efficacy, and acquiring HIV during partial adherence risks drug resistance, so testing and clinical oversight are required.
Who profits, and who pushes back
Nobody is named here yet, because we have not done that work on this entry. Read that as unfinished. Somebody almost certainly sells this, and somebody almost certainly disputes it. Assume both until we have checked.
At a glance
- Oral PrEP efficacy (adherent)
- ~99% reduction in sexual acquisition
- On-demand 2-1-1 source
- IPERGAY trial (MSM)
- Injectable
- Cabotegravir LA (Apretude), every 2 months
- Injectable evidence
- HPTN 083 (superior to oral in MSM/TGW)
- Monitoring
- HIV test before and during; renal/STI screening
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about PrEP (HIV Pre-Exposure Prophylaxis). A short entry is not a safe entry.
- Cost and market. We have not documented what it sells for or who sells it.
- Supply chain. We have not mapped where it is made.
- Who uses it. We have not documented the user groups.
- What could change. No forward-looking summary yet.
- How it compares. We have not set it against the alternatives.
- Children and teenagers. We have not checked what is known about younger people.
- Where we land. We have not taken a position on this yet.
Sources
The studies below are named and described, but not linked. You cannot open them from here and check our reading against them, which means this page is our summary of the literature rather than a document you can verify. Weigh it accordingly until the links exist.
The studies that matter
Grant et al. (iPrEx), NEJM2010
First major RCT showing oral TDF/FTC PrEP reduced HIV acquisition in MSM, strongly adherence-dependent
Molina et al. (IPERGAY), NEJM2015
On-demand 2-1-1 TDF/FTC reduced HIV incidence by ~86% in high-risk MSM
Landovitz et al. (HPTN 083), NEJM2021
Long-acting injectable cabotegravir superior to daily oral TDF/FTC for HIV prevention in MSM and transgender women
Delany-Moretlwe et al. (HPTN 084), Lancet2022
Injectable cabotegravir superior to oral TDF/FTC in cisgender women