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Post-exposure doxycycline helps reduce the risk for some sexually transmitted infections

Over the past decade there has been a resurgence of common sexually transmitted infections (STIs), including bacterial STIs such as syphilis, gonorrhea and chlamydia.

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These STIs can cause serious complications, as follows:

  • syphilis – the germs that cause this STI can attack nerves in the eyes (causing blindness) and ears (causing loss of hearing). Syphilis can also injure the heart, brain, kidneys and liver.
  • gonorrhea – this STI can cause pain and discomfort. It can also cause infertility. Over the past 50 years, gonorrhea-causing germs have acquired the ability to resist different antibiotics and there are fewer treatment options today.
  • chlamydia – this STI can cause pelvic inflammatory disease and infertility in women. Complications from chlamydia are less common in men, though it can cause inflammation in the testicles and prostate.

Researchers in San Francisco and Seattle conducted a study with the antibiotic doxycycline to assess if it could reduce the risk of syphilis, gonorrhea and chlamydia when taken after sexual exposure. Participants were mostly gay, bisexual and other men who have sex with men (gbMSM); a small proportion of participants (less than 5%) were transgender women.

At the start of the study, 501 participants were screened for STIs and provided treatment if needed. Once in the study, participants were randomly assigned to either take 200 mg doxycycline (doxy-PEP) within 72 hours of condomless sex or no doxycycline. Participants visited study clinics every three months for STI screening and to answer surveys about sexual behaviour, adherence and reports of side effects. Researchers monitored participants for at least one year.

Overall, doxy-PEP reduced the risk of syphilis, gonorrhea and chlamydia by two-thirds. This was statistically significant. Doxy-PEP was highly effective at reducing the risk of STIs whether or not participants had HIV.

Adherence to doxy-PEP was high (around 86%), suggesting a highly motivated group of participants.

Study details

Researchers reported results on 501 participants who were randomized in a 2:1 ratio to one of two groups:

  • Doxy-PEP group – these people were given bottles of delayed-release tablets of 200 mg doxycycline and told to take one within 72 hours of condomless sex. 
  • Standard care group – these people were not given doxy-PEP

As mentioned previously, all participants visited study clinics every three months. If they needed to, they could visit the study clinics more frequently.

Researchers recruited 174 HIV-positive people and 327 HIV-negative people. The HIV-negative people were taking pre-exposure prophylaxis (PrEP) to reduce their risk for acquiring HIV.

The average profile of participants upon study entry was as follows:

  • age – 38 years
  • 96% cisgender men; 4% transgender women or gender-diverse people
  • major ethno-racial groups: White – 67%; multiple races – 15%; Asian – 11%; Black – 7%
  • STIs in the past six months: gonorrhea – 30%; chlamydia – 12%; syphilis – 4%
  • number of sexual partners in the past three months – nine
  • engaged in transactional sex at any time in the past – 29%
  • commonly used drugs in the past three months: marijuana – 48%; poppers – 45%; ecstasy, GHB or ketamine – 32%; opioids – 3%; stimulants (meth, cocaine or crack) – 30%

HIV-related characteristics

Among participants with HIV at the start of the study, more than 99% were taking HIV treatment (ART) and 95% of ART users had a suppressed viral load (less than 50 copies/mL). Their average CD4+ count was 700 cells/mm3.

In nine HIV-positive people, their viral load at the start of the study was detectable (an average of 1,354 copies/mL).

The study was done from August 2020 through May 2022.

Results – overall STI diagnoses

Overall, the use of doxy-PEP reduced the risk of developing bacterial STIs (syphilis, gonorrhea or chlamydia) by 66%.

People taking HIV PrEP

Among HIV-negative people taking PrEP, an STI was diagnosed in 11% of clinic visits in people who were also taking doxy-PEP vs. 32% who did not receive doxy-PEP.

People with HIV

Among HIV-positive people, an STI was diagnosed in 12% of clinic visits in people who were taking doxy-PEP vs. 31% who did not receive doxy-PEP.

Results – specific STIs

Gonorrhea

Among HIV-negative people taking PrEP, gonorrhea was diagnosed in 9% of people who took doxy-PEP vs. 20% of people who did not receive doxy-PEP.

Among people with HIV, gonorrhea was diagnosed in 9% of people who took doxy-PEP vs. 20% of people who did not receive doxy-PEP.

Chlamydia

Among HIV-negative people taking PrEP, chlamydia was diagnosed in 1% of people who took doxy-PEP vs. 12% of people who did not receive doxy-PEP.

Among people with HIV, chlamydia was diagnosed in 4% of people who took doxy-PEP vs. 15% of people who did not receive doxy-PEP.

Syphilis

Among HIV-negative people taking PrEP, syphilis was diagnosed in 0.4% of people who took doxy-PEP vs. 3% of people who did not receive it.

Among people with HIV, syphilis was diagnosed in 1% of people who were taking doxy-PEP vs. 2% of people who did not receive it.

Safety

In general, doxy-PEP was well tolerated. Only 2% of people who were given doxycycline-PEP stopped taking it because of side effects or other reasons. This is not surprising, as doxycycline has been in use as a treatment for different bacterial infections for decades and has a good track record.

According to the researchers, the following adverse events were probably caused by use of doxycycline:

  • 2 people had temporarily increased levels of liver enzymes in their blood
  • 3 people had temporary severe diarrhea
  • 2 people had temporary severe headaches

There was a modest degree of weight loss in people who took doxy-PEP (0.8 kg) and there was a very modest degree of weight loss among people not taking the antibiotic (0.2 kg).

When surveyed, nearly 90% of participants agreed that doxy-PEP was acceptable or very acceptable for them.

Resistance

As with the use of any antibiotic, there are concerns that bacteria, particularly STIs, may develop the ability to resist the effects of antibiotics. Researchers performed analyses of swabs taken from participants at different times in the study. However, antibiotic resistance was not common and the researchers did not think that it was a significant issue.

Gonorrhea resistance

For many reasons, researchers were only able to get a limited number of gonorrhea-causing bacteria for analysis (from 17% of participants). At the start of the study, doxycycline resistance was found in four out of 15 samples (27%). During the study, the distribution of gonorrhea that was resistant to doxycycline was as follows:

  • people taking doxy-PEP – 38% (5 out of 13 samples)
  • people not taking doxy-PEP – 12% (2 out of 16 samples)

Staph aureus

Another bacterium of interest is Staphylococcus aureus (S. aureus). It lives on the skin and some mucosal surfaces (such as inside the nose). The skin and lining of the nose act as barriers preventing the bacteria from getting inside the body. As this bacterium rarely gets inside the body, the immune system does not have experience dealing with it and can become overwhelmed when S. aureus gets inside because of cuts or breaks in the skin. Once inside the body, S. aureus can spread to tissues and, via the blood, to vital organs such as the heart and lungs, where it can cause serious and sometimes deadly infection.

At the start of the study, S. aureus was found in swabs of the nasal cavity in 45% of all participants and it was resistant to doxycycline in 12% of participants.

After 12 months of the study, 28% of participants taking doxy-PEP had S. aureus in their nasal samples vs. 47% in participants not taking doxy-PEP.

The researchers stated that, overall, resistant S. aureus was found in 5% of people taking doxy-PEP and in 4% of people not taking the antibiotic.

Bear in mind

The use of doxy-PEP in this study, which consisted of highly motivated gbMSM and transgender women participants, was very effective at minimizing the onset of chlamydia, gonorrhea and syphilis. As a result, doctors will be interested in prescribing this antibiotic for some, perhaps many, of their sexually active gbMSM patients who can adhere to doxy-PEP.

Some public health departments in California have recommended the use of doxy-PEP for gbMSM. However, at the time we went to publication, Public Health England and the British Association for Sexual Health and HIV do not recommend its use for fear of creating more and widespread strains of bacteria resistant to doxycycline (and related antibiotics).

As mentioned earlier, there are fewer treatment options for gonorrhea due to the development of resistance. Long-term monitoring for the possibility of gonorrhea (and other bacteria) becoming resistant to doxycycline needs to be done, particularly in populations of gbMSM. This is important, as some laboratory experiments suggest that bacteria that become resistant to doxycycline may also somehow acquire the ability to resist unrelated antibiotics such as ceftriaxone.

The long-term effect of doxycycline on bacteria that naturally live in the gut and are necessary for human health also needs to be studied.

The present study was focused on highly motivated gbMSM and 19 transgender women (or gender diverse people). Studies of doxy-PEP need to be designed for other populations at high risk of STIs.

—Sean R. Hosein

REFERENCES:

  1. Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure doxycycline to prevent bacterial sexually transmitted infections. New England Journal of Medicine. 2023 Apr 6;388(14):1296-1306.
  2. Vanbaelen T, Manoharan-Basil SS, Kenyon C. Doxycycline post-exposure prophylaxis could induce cross-resistance to other classes of antimicrobials in Neisseria gonorrhoeae: an in-silico analysis. Sexually Transmitted Diseases. 2023; in press.
  3. Mortimer TD, Grad YH. A genomic perspective on the near-term impact of doxycycline post-exposure prophylaxis on Neisseria gonorrhoeae antimicrobial resistance. Clinical Infectious Diseases. 2023; in press.
  4. Whiley DM, Tickner JA, Kundu RL, et al. Selection of Neisseria gonorrhoeae ceftriaxone resistance using doxycycline post-exposure prophylaxis. Lancet Infectious Diseases. 2023; in press.
  5. Kong FYS, Kenyon C, Unemo M. Important considerations regarding the widespread use of doxycycline chemoprophylaxis against sexually transmitted infections. Journal of Antimicrobial Chemotherapy. 2023 Jul 5;78(7):1561-1568.