Several effective strategies can lower your risk of sexually transmitted infections without relying on condoms. Some are medications, some are vaccines, and some involve how you and your partners approach testing and communication. No single method protects against everything, so the strongest approach combines multiple layers of protection tailored to your situation.
PrEP for HIV Prevention
Pre-exposure prophylaxis, or PrEP, is a prescription medication that reduces the risk of getting HIV from sex by about 99% when taken as prescribed. It’s available as a daily pill or as a long-acting injection given every two months. For people who inject drugs, PrEP reduces HIV risk by at least 74%.
PrEP only protects against HIV, not other STIs. But it’s one of the most effective tools available for people who are sexually active and want peace of mind about HIV specifically. Your provider can prescribe it whether you’re in a relationship with someone who is HIV-positive or simply want an extra layer of protection.
Undetectable Viral Load Eliminates HIV Transmission
If your partner is living with HIV and takes antiretroviral therapy consistently enough to maintain an undetectable viral load, the risk of transmitting HIV to you through sex is zero. This is the principle behind “Undetectable = Untransmittable,” or U=U, which the CDC has confirmed. This means that effective HIV treatment doubles as complete prevention for sexual partners.
Doxy-PEP for Bacterial STIs
A newer prevention tool called doxy-PEP uses the antibiotic doxycycline taken after sex to reduce the risk of bacterial infections like syphilis, chlamydia, and in some studies, gonorrhea. The CDC released clinical guidelines for this strategy in 2024, recommending it for gay, bisexual, and other men who have sex with men, as well as transgender women at increased risk for STIs.
The dose is 200 mg taken as soon as possible after oral, vaginal, or anal sex, but no later than 72 hours afterward. You should not take more than 200 mg in any 24-hour period. Doxy-PEP requires a prescription, so you’ll need to discuss it with a provider who can assess whether it’s appropriate for your risk profile.
Vaccines That Prevent STIs
Two vaccines directly prevent sexually transmitted infections, and both are widely available.
The HPV vaccine protects against the strains of human papillomavirus most likely to cause genital warts and cancers of the cervix, throat, anus, and penis. More than 15 years of data show it provides safe, effective, and long-lasting protection. If you’re between 15 and 26, the standard schedule is three doses spread over six months. Adults between 27 and 45 who weren’t vaccinated earlier can still get it after discussing the benefits with a provider, though protection is somewhat lower in this age range because more people have already been exposed to HPV.
The hepatitis B vaccine prevents a virus that spreads through sexual contact, shared needles, and childbirth. It requires completing the full series of shots to give you long-term protection, and the CDC considers it the single best way to prevent hepatitis B infection.
Regular Testing as a Prevention Strategy
Routine STI screening doesn’t stop infections from happening, but it catches them early enough to treat before you unknowingly pass them to someone else. Many STIs, particularly chlamydia, gonorrhea, and syphilis, cause no symptoms for weeks or months. Testing turns invisible infections into treatable ones.
How often you should test depends on your situation. Sexually active women under 25 should be screened for chlamydia and gonorrhea annually, as should women 25 and older who have new or multiple partners. Men who have sex with men should test for chlamydia, gonorrhea, syphilis, and HIV at least once a year, and every three to six months if they’re on PrEP, living with HIV, or have multiple partners. All adults should be screened for hepatitis C at least once, and everyone between 13 and 64 should have at least one HIV test.
Testing at the right intervals means that even if you do pick up an infection, it gets treated quickly. This is especially important for syphilis, which progresses through stages and becomes harder to treat over time.
Making Sure Partners Get Treated Too
One of the most common ways people get reinfected with an STI is by resuming sex with a partner who was never treated. Expedited partner therapy, or EPT, allows your provider to prescribe treatment for your sexual partner without requiring them to come in for a separate appointment. Studies show EPT reduces chlamydia reinfection rates and increases the likelihood that partners actually complete treatment compared to simply asking someone to go get tested on their own.
If you test positive for chlamydia or gonorrhea, ask your provider whether EPT is available in your state. Notifying partners is uncomfortable, but reinfection is preventable if both people get treated at the same time.
Why Mutual Monogamy Is Complicated
Staying in a mutually monogamous relationship with a partner who has tested negative for STIs is often listed as a prevention strategy, and in theory it works. In practice, research tells a more nuanced story. A review of the evidence found that people’s compliance with monogamy tends to be low, similar to compliance rates with other medical advice. People who identify as monogamous are also less likely to use other safer sex practices than people in openly non-monogamous arrangements, which can create a false sense of security.
This doesn’t mean monogamy is useless as a strategy. It means that both partners need to have been recently tested, need to share the same definition of what monogamy means, and need to be honest if the agreement changes. Monogamy works best as a layer of protection alongside testing rather than as the only thing you rely on.
What to Avoid: Spermicides Don’t Help
Products containing the spermicide nonoxynol-9 are sometimes assumed to offer STI protection because they kill sperm. They don’t protect against infections, and frequent use actually increases risk. A Cochrane review found that nonoxynol-9 significantly increased the likelihood of genital lesions, which are open sores on vaginal tissue. Those lesions, in turn, were associated with roughly double the risk of acquiring HIV. The damage appears to come from disruption of normal vaginal bacteria, leading to yeast infections and direct tissue irritation. Spermicides should not be considered part of any STI prevention plan.
Layering Your Protection
The most effective approach combines several of these strategies based on which infections concern you most. PrEP handles HIV. Vaccines handle HPV and hepatitis B. Doxy-PEP can reduce bacterial STIs for those who qualify. Regular testing catches what slips through. None of these methods requires a condom, and each one addresses a different gap in protection.
Talk to a provider about which combination makes sense for your sexual activity, your partners, and your risk factors. The goal isn’t to find a single replacement for condoms. It’s to build a set of tools that, together, give you strong and realistic protection.