DoxyPEP is post-exposure prophylaxis with doxycycline against chlamydia (including the subtype lymphogranuloma venereum or LGV) and against syphilis with an antibiotic called doxycycline. Doxycycline remains a specific treatment for chlamydia and an alternative for syphilis treatment. This antibiotic can now be used off-label (without official recommendation in Canada) as prevention for these two infections. DoxyPPE, to be effective, must ideally be taken within the first 24 hours after a sexual encounter but not exceeding 72 hours after, taken as a single dose of 200mg of doxycycline orally once.
DoxyPrEP is pre-exposure prophylaxis with doxycycline against chlamydia (including the subtype lymphogranuloma venereum or LGV) and against syphilis with an antibiotic called doxycycline. Doxycycline remains a specific treatment for chlamydia and an alternative for syphilis treatment. This antibiotic can now be used off-label (without official recommendation in Canada) as prevention for these two infections. DoxyPrPE, to be effective, must be taken before anticipated exposure and subsequently every day during periods of repeated anticipated exposures; The suggested dosage is 100mg of doxycycline orally once daily during periods of high-risk exposure to chlamydia or syphilis.
The effectiveness of doxyPPE and doxyPrPE is over 50% and is related to its adherence. For doxyPPE to be effective, it must be taken ideally within the first 24 hours following exposure without exceeding the 72-hour limit. DoxyPrPE, to be effective, must be taken daily. According to different studies, the effectiveness of doxyPPE and doxyPrPE varies but is always greater than 50%.
ANRS IPERGAY (doxyPPE), between July 20, 2015, and January 21, 2016, in France, randomized study with radio 1:1, open, 232 male participants at birth, 116 under doxyPPE and 116 control group, effectiveness against all STIs was 47%, against chlamydia relative reduction of 70%, against syphilis relative reduction of 73%, no significant difference in prevention against gonorrhea, no resistance against chlamydia or syphilis to doxycycline.
DoxyPEP study (doxyPEP), between November 26, 2019, and May 13, 2023 (estimated end) in San Francisco, California, stopped early on May 13, 2022, due to significant effectiveness of both cohorts, randomized study with ratio 2 doxyPPE: 1 non-doxyPPE, open, 390 anticipated participants but 637 recruited, 501 under doxyPEP including 174 living with HIV and 327 under PrEP, male at birth, effectiveness against all STIs was 62% in people living with HIV (PLHIV) and 66% in those under PrEP, against chlamydia relative reduction of 74% in PLHIV and 88% in those under PrEP, against syphilis relative reduction of 77% in PLHIV and 87% in those under PrEP. This study was the only one to demonstrate effectiveness in preventing gonorrhea with a relative reduction of 55% in PLHIV and 57% in those under PrEP. No resistance was observed against chlamydia or syphilis to doxycycline. The use of doxyPPE or doxyPrEP may increase or does increase the risk of gonorrhea resistance to tetracyclines.
dPEP Kenya - between February 5, 2020, and October 30, 2022, in Kenya, randomized study with ratio 1:1, open, 443 anticipated participants and 449 recruited, all women between 18-30 years old. The end of the study is estimated for June 30, 2024. Preliminary results demonstrate preventive efficacy against chlamydia and syphilis.
ANRS 174 DoxyVAC - January 19, 2021, and June 2022, in France, recruitment of study participants from ANRS Prévenir, randomized study, blind with radio 2:1 for doxyPEP and 1:1 for meningococcal B vaccine (Boxsero), 720 participants, HARSAH under PrEP non-HIV, divided into 2 intervention groups: Intervention 1: PPE with doxycycline or without PPE, randomization with ratio 2 with dPPE: 1 without dPPE; Intervention 2: Meningococcal B vaccine (Bexsero®) versus no vaccine with randomization ratio 1:1. The Bexsero® vaccine administered in two doses with 2-month intervals (0-2 months) versus no vaccine. Randomization was planned in 4 arms: Arm 1: doxycycline and Bexsero® vaccine (240 participants; Arm 2: doxycycline without Bexsero® vaccine (240 participants); Arm 3: Bexsero® vaccine without doxycycline (120 participants); Arm 4: no doxycycline or Bexsero® vaccine (120 participants). The study was stopped early due to its significant effectiveness and with recommendation of doxyPPE and Bexsero® vaccine to all participants.
The DuDHS Study - continuous doxycycline (doxyPrEP) in Vancouver and Toronto, Canada, between May 2018 and June 2019, HARSAH, trans women under PrEP and non-HIV, 52 participants with radio 1:1, study duration 48 weeks, one arm starting immediately and the other deferred by 24 weeks. In the immediate arm no cases of chlamydia or syphilis were reported. In the deferred arm, 10 cases of chlamydia, 1 of syphilis were reported in the first 24 weeks of the study and none thereafter. 4 cases of gonorrhea were reported in the immediate arm versus 8 in the deferred arm in the first 24 weeks of the study and 1 case in the immediate group after 24 weeks.
DaDHS - continuous doxycycline (doxyPrEP), between August 15, 2019, and June 30, 2021, in Vancouver and Toronto, Canada, men living with HIV, 52 participants with radio 1:1, study duration 48 weeks, final results pending.
Syphilaxis - continuous doxycycline (doxyPrEP), in Australia, 350 participants, single arm, male at birth. Results pending.
It is important to know that data on the long-term use of doxycycline is limited.
The most common side effects are photosensitivity (risk of burns, erythema, skin rashes with sun exposure), heartburn (acidity / gastric reflux), nausea, vomiting, diarrhea, and headaches secondary to increased benign intracranial pressure. If these side effects occur, the medication should be stopped and the doctor or IPS consulted. To prevent gastrointestinal side effects, doxycycline should be taken with a large glass of water and not lying down for 1 to 2 hours after taking the antibiotic. To avoid photosensitivity, it is recommended to use adequate sunscreen, avoid sun exposure and if impossible or ineffective, to stop the medication during the potential sun exposure period.
Serious side effects, although rare, include tooth discoloration, gastric/esophageal ulcers, exacerbation of autoimmune diseases including systemic lupus erythematosus, dermatitis including a severe dermatitis called Steven-Johnson or toxic epidermal necrolysis, hemolytic anemia, neutropenia (decreased neutrophils, a type of white blood cells), hepatotoxicity (toxic effect of the medication on the liver) and pancreatitis (inflammation of the pancreas). The medication could also cause a severe allergic reaction (anaphylaxis) in people allergic to tetracyclines.
Doxycycline is contraindicated with the intake of acitretin, filbanserin, isotretinoin (acne medication), lomitapide (medication for familial hypercholesterolemia), lonafarnib, strontium ranelate, tretinoin (medication used in the cream called Retin-A or Stieva) and live vaccines for typhoid fever and tuberculosis (BCG). Before starting doxycycline, it is necessary to consult the pharmacist with the up-to-date list of medications to check for possible drug interactions.
Doxycycline should be taken with a large glass of water. It can be taken with food. However, it should not be taken with iron supplements, multivitamins, calcium or magnesium supplements including antacid medications like Rolaid or Tums, or with laxatives. These supplements bind to doxycycline, reducing its absorption and effectiveness.
It should be noted that neither doxyPPE nor doxyPrPE are officially recommended in Canada. Its use is currently off-label.
It is also important to know that data on the long-term use of doxycycline is still limited although we have more and more studies on its use in doxyPPE and doxyPrPE.
In doxyPPE, doxycycline was studied with a dose of 200mg taken once within 72 hours following potential exposure to chlamydia or syphilis. Ideally, it should be taken within the first 24 hours without exceeding the 72-hour limit.
In doxyPrPE, doxycycline was studied with a single tablet of 100mg taken once daily at the same time. It should be taken before anticipated exposure to chlamydia or syphilis and then daily during anticipated exposure periods, and stopped after the risk of exposure to these two STIs is eliminated.
At La Licorne, we have a study project on the use of doxycycline in doxyPPE with two tablets taken once daily, at the same time, for 2 to 3 days.