References UK clinical guidance from the NHS, the British HIV Association (BHIVA), and the British Association for Sexual Health and HIV (BASHH). Last updated: April 2026.
PrEP (pre-exposure prophylaxis) is extremely effective at preventing HIV, but there’s a small theoretical risk of drug resistance if someone takes PrEP while they already have undiagnosed HIV. This is why HIV testing before starting PrEP, and regular testing every three months, is essential.
Understanding this risk helps explain the testing protocols and reassures why PrEP is safe when taken correctly.
Need an HIV test before starting PrEP? Order a home kit
How Could PrEP Cause Resistance?
PrEP contains two drugs: tenofovir and emtricitabine. These drugs alone cannot suppress an active HIV infection. A complete HIV treatment regimen needs at least three drugs from two different classes.
If someone has undiagnosed HIV and starts PrEP (just the two-drug combination), the virus is exposed to these drugs at levels that aren’t high enough to fully suppress it. Over time, HIV can develop mutations that make it resistant to tenofovir and/or emtricitabine.
This matters because if the person is later diagnosed with HIV, they may have resistance to drugs that would otherwise be first-line treatment.
How Common Is It?
Very rare. Studies of large PrEP programmes show resistance develops in fewer than 1 in 1,000 PrEP users. Almost all documented cases involved people who were in the acute window period (just infected, HIV undetectable by standard tests) when starting PrEP, or who didn’t test regularly.
How to Prevent Resistance
- Get an HIV test before starting PrEP — this confirms you’re HIV-negative before beginning
- Test every 3 months while on PrEP — catches any new infection early
- Use the acute HIV test (4th generation) — detects infection earlier than antibody-only tests
- Take PrEP consistently — inconsistent dosing creates drug levels that can promote resistance
- If you experience flu-like symptoms after possible exposure while on PrEP, tell your clinic immediately
Read more: What is PrEP? | HIV drug resistance | What is HIV?
Frequently Asked Questions
Should I worry about resistance if I’m on PrEP?
No. The risk is very low when PrEP is taken correctly with regular testing. The benefits of PrEP (99% HIV prevention when taken consistently) far outweigh this small risk.
What happens if I test positive while on PrEP?
Your clinic will do additional tests (including resistance testing) and switch you to full HIV treatment. Most people with PrEP breakthrough infections can be treated successfully, though treatment options may be slightly limited if resistance is present.
Related reading
- Are HIV Tests Accurate If You're on PrEP, PEP or ART?
- Choosing the Right PrEP Drug: Truvada vs Descovy
- Post-Exposure Prophylaxis (PEP) for HIV
- Pre-Exposure Prophylaxis (PrEP) for HIV
- PrEP and Sexually Transmitted Infections
Sources
- NHS — Sexual health conditions
- BASHH — UK clinical guidelines for STI management
- British HIV Association (BHIVA) — HIV treatment guidelines
- Terrence Higgins Trust — sexual health information
- UK Health Security Agency — STI surveillance data
Steve Page is a recognised expert on Sexually Transmitted Diseases (STDs) and STD treatments, having published numerous articles in peer-reviewed journals and presented his research at conferences around the world. He has an in-depth understanding of the latest medical research on STDs, and is an advocate for the development of new treatments and protocols to improve the health of those affected. In addition to his research, he has dedicated his career to understanding the causes and symptoms of STDs, as well as how to best treat those impacted.
