What is the role of doxycycline (DOXY) post-exposure prophylaxis (PEP) in preventing sexually transmitted infections (STIs)?

Doxycycline Post-Exposure Prophylaxis for STI Prevention

The CDC recommends doxycycline post-exposure prophylaxis (doxy PEP) at 200 mg taken within 72 hours after condomless sex for gay, bisexual, and other men who have sex with men (MSM) and transgender women who have had at least one bacterial STI in the past 12 months. 1, 2

Who Should Receive Doxy PEP

Strongly Recommended

• MSM and transgender women with at least one bacterial STI (syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months should be offered doxy PEP through shared decision-making 1, 2, 3
• This represents the primary target population with the strongest evidence base 4

May Be Considered

• MSM and transgender women without a recent bacterial STI but who will participate in sexual activities with increased STI exposure risk could be discussed for doxy PEP using shared decision-making 2

Not Currently Recommended

• Insufficient evidence exists to recommend doxy PEP for cisgender heterosexual men, cisgender women, transgender men, and other queer/nonbinary persons 2, 4
• The evidence base is limited to MSM and transgender women populations 1

Efficacy Data

Doxy PEP demonstrates substantial protective effects against bacterial STIs:

• Reduces syphilis and chlamydia infections by more than 70% 2, 3
• Reduces gonococcal infections by approximately 50% 2, 3
• The DoxyPEP trial showed STIs were present in only 12% of quarters in the doxy-PEP group versus 30.5% in the standard-care group (relative risk 0.39, p<0.0001) 5

Dosing and Administration Protocol

Core Dosing Instructions

• 200 mg doxycycline (any formulation) taken as a single dose within 72 hours after oral, vaginal, or anal sex 1, 2, 4
• Take as soon as possible after sexual exposure, ideally sooner rather than waiting the full 72 hours 1
• Maximum dose: 200 mg per 24-hour period 1, 2, 4

Administration Technique to Minimize Side Effects

• Take on a full stomach with a full glass of liquid (at least 200 mL of water) 2, 4
• Remain upright for at least 1 hour after taking to prevent esophagitis 2, 4
• Separate doxycycline dose by at least 2 hours from dairy products, antacids, and supplements containing calcium, iron, magnesium, or sodium bicarbonate 1, 4

Prescription Strategy

• Provide enough doses based on the person's anticipated sexual activity until their next visit 1, 2
• This requires individualized behavioral assessment through shared decision-making 1

Initial Visit Protocol

When initiating doxy PEP, clinicians should:

Baseline Testing

• Screen for gonorrhea and chlamydia at all anatomic sites of exposure (oral, rectal, urogenital) 1, 4
• Perform serologic testing for syphilis 1, 4
• HIV screening for HIV-negative individuals per CDC HIV PrEP guidelines 1, 4

Patient Counseling

• Discuss potential side effects including photosensitivity, esophagitis, and gastrointestinal intolerance (nausea, vomiting, diarrhea) 2, 4
• Counsel on drug interactions, particularly with dairy products and supplements 1
• No clinically relevant interactions exist between doxycycline and gender-affirming hormonal therapy 1
• Review the patient's complete medication list, including over-the-counter medications, to assess for drug interactions 1

Comprehensive Prevention Approach

• Provide risk reduction counseling and condoms 1, 4
• Encourage HIV PrEP for HIV-negative individuals when indicated 1, 4
• Assess need for HIV PEP if recent high-risk exposure 1
• Confirm or encourage linkage to HIV care for persons living with HIV 1

Follow-Up and Monitoring

Screening Schedule

• Screen for gonorrhea and chlamydia at anatomic sites of exposure and syphilis every 3-6 months 1, 2, 3
• For HIV-negative individuals on HIV PrEP, follow CDC HIV PrEP screening guidelines 1, 4
• For HIV-negative individuals not on HIV PrEP, consider HIV screening every 3-6 months 1, 2

Ongoing Assessment

• Assess for side effects from doxycycline at each visit 1, 2
• Re-assess continued need for doxy PEP every 3-6 months 2, 4
• Provide risk reduction counseling and condoms at each visit 1, 4
• Prescribe enough doses until the next follow-up visit based on behavioral assessment 1

Important Caveats and Limitations

Spectrum of Coverage

• Doxy PEP does not prevent Mycoplasma genitalium infections 3
• Patients must understand that doxy PEP provides protection only against syphilis, chlamydia, and gonorrhea, not all STIs 3
• Regular comprehensive STI screening remains essential even with doxy PEP use 3

Antimicrobial Resistance Concerns

• The DoxyPEP trial found similar rates of tetracycline resistance in gonorrhea isolates between doxy-PEP users (27%) and non-users (24%) 5
• Ongoing studies continue to evaluate antimicrobial resistance patterns and population-level impact 1, 4
• Some experts recommend doxy PEP be used more selectively rather than as a broad population-level intervention 6

Prescribing Efficiency

• Research suggests that prescribing doxy PEP for 12 months after STI diagnosis would reduce the proportion using doxy PEP to 38% while still averting 39% of STI diagnoses 7
• The most efficient prescribing strategies are based on STI history rather than HIV status or PrEP use alone 7

Safety Profile

• Doxy PEP was well tolerated in clinical trials with only one grade 2 laboratory abnormality and five grade 3 adverse events possibly or probably related to doxy-PEP 5
• No serious adverse events were attributed to doxycycline in the DoxyPEP trial 5
• Chronic alcohol consumption may reduce serum levels of doxycycline, potentially decreasing efficacy 4

Clinical Implementation Algorithm

1. Identify eligible patients: MSM or transgender women with ≥1 bacterial STI in past 12 months 1, 2
2. Perform baseline testing: Gonorrhea/chlamydia at all exposure sites, syphilis serology, HIV screening 1, 4
3. Prescribe 200 mg doxycycline with clear instructions on timing (within 72 hours after sex) and administration technique 1, 2
4. Provide comprehensive counseling on side effects, drug interactions, and continued need for condoms and other prevention strategies 1, 2
5. Schedule follow-up every 3-6 months for STI screening, side effect assessment, and re-evaluation of ongoing need 1, 2