Reducing STI Risk With Doxycycline: Is It a Good Idea?

A phase 4 clinical trial shows early data that taking doxycycline within 72 hours of unprotected sex lessens sexually transmitted infection (STI) risk. But is this a safe practice? Is this recommended by medical professionals?

With antimicrobial resistance (AMR) on the rise, preventing STIs remains key. Ideally, people should practice safe sex rather than reaching for a curative after the fact.

Doxycycline pre-exposure prophylaxis (PEP), yes or no?

Suppose someone had unprotected sex and, within three days, discovers that their partner may have had an STI. Should they take a single doxycycline dose (antibiotic) to prevent possible disease? Though initial studies suggest this may decrease the risk of syphilis and chlamydia, is this practice recommended?

Sexually transmitted infections (STIs) in the U.S.

So, why care about STIs? While many people never become exposed, others are more likely to develop an infection based on lifestyle choices, healthcare inaccessibility, and other factors.

According to the most recent Centers for Disease Control and Prevention (CDC) data, about one out of five people developed an STI in 2018. Furthermore, in addition to causing pain and suffering, STIs cost the U.S. healthcare system almost $16 billion annually. Because STIs often remain untreated or undetected, these figures greatly underestimate the numbers affected. Sadly, fifty percent of these newly acquired infections occur in Americans aged 15 to 24. Something needs to be done to curtail increasing infection rates.

Doxycycline PEP phase 4 clinical trial

Research question

Two studies to date report that using doxycycline as PEP decreases STIs in the men having sex with men (MSM) population subset. One study, led by Dr. Anne Luetkemeyer of the University of C.A., San Francisco, is a phase 4 clinical trial.

The CDC favors Dr. Leutkemeyer and colleagues' research that may support doxycycline PEPn as a method for decreasing STIs in MSM at-risk communities. However, while weighing public health and individual health risks and benefits, the CDC fails to mention concerns about the dangers of increasing AMR. While research suggests that doxycycline PEP may be effective to decrease the rate of STIs, the focus in at-risk populations should center on prevention and safe sex practices rather than emphasizing doxycycline PEPt.

Study limitations

In the clinical trial by Leutkemeyer et al., patients were randomized to receive doxycycline (treatment group) or not (controls). However, the patients and researchers knew if they were treatments or controls. This increases the risk of bias and complicates result interpretation.

Additionally, how a participant used the antibiotic was left up to the individual (how often taken). The participants were a very narrow subset of the population. They included only males born male at birth with HIV or who were on HIV pre-exposure prophylaxis (PrEP). Further criteria included a history of bacterial STIs and condomless sex with another male in the past 365 days. Participants were permitted to stop or start PrEP throughout the trial, which complicates data interpretation.

The study’s main outcome measure was the development of one or more bacterial STIs occurring each quarter of the year. According to Luetkemeyer et al. study, sufficient data demonstrated a reduced incidence of STIs in those receiving the antibiotics. Upon a CDC review of the results, they agreed that improvement was shown in patients suffering from chlamydia and syphilis. However, no improvements were seen in the rate of gonorrhea infections.

Further concerns and study limitations include:

Small sample size (637 individuals).

Participants could choose how often they took antibiotics with 50% taking less than 10 monthly doses but many took over 10 doses per month. This complicates interpreting the effectiveness of a single dose of doxycycline within 72 hours of condomless sex. 20% of patients with gonorrhea had tetracycline-resistant infections (AMR). The presence of tetracycline resistance in the same drug class as doxycycline is concerning. Resistance could have already existed, however, the use of the doxycycline PEP could have created drug resistance, and studies are lacking to better explain this g factor.

What we don’t yet know

The CDC, while encouraged by data suggesting that in a very narrow subset of the population with a high risk of STIs and other underlying health issues, doxycycline PEP may reduce the risk of some STIs. However, they are not making a blanket statement to use doxycycline-like candy in place of protected sex.

The CDC has stated that “doxy-PEP as a targeted intervention for bacterial STIs has the potential to reduce STI acquisition and transmission.” But they emphasize that additional research is needed.

Factors need to be weighed, and additional research specifically defining:

For what subset of the population should this type of PEP be used?

What are the individual health benefits and risks?

What frequency of administration is needed to statistically decrease the infection rate and improve protection?

What are the global public health risks (such as AMR) vs. benefits (lowering the currently increasing STI rates)?

Should this PEP be available on demand?

Doxycycline on-demand?

Is doxy PEP use justified? It may be reasonable to use in special cases where an STI risk is high and accidental exposure occurred (a condom breaks or the partner wasn’t upfront about infection). But it shouldn’t be available on-demand.

The concept of on-demand doxycycline causes concern as it allows too much access to an antibiotic that, at this point, has minimal AMR associated with it. In both human and animal medicine, this antibiotic performs a crucial role. It treats countless respiratory, skin, infectious tick-borne diseases, and many STIs.

Providing easy access to an antibiotic, like doxycycline, for patients to use at will, is inappropriate antibiotic use. It could lead to organisms developing further resistance to the drug, making it ineffective for many diseases across many species. If that occurs, we could be back in the dark ages, trying to treat conditions for which doxycycline remains our top or only choice.

Still, we must keep in mind that while doxycycline PEP isn’t appropriate for the general population, multiple factors increase the risk of STIs in certain groups. These include health inequities, lack of healthcare access, and many other disparities. Therefore considering doxycycline PEP for a small subset of the population may aid in decreasing the U.S.’s overall STI health burden.

STI prevention

While studies suggest that using doxycycline PEP may prove effective, in reducing STI rates, prevention remains key, and knowingly having unprotected sex increases infection risks. If you do not know your sexual partners well, are part of a community where STIs may be more commonly transmitted, are HIV positive, or are on PrEP, you could be at higher risk. Why take the risk?

AMR, a global health concern

If you become exposed after unprotected sexual contact, would doxycycline help prevent infection? Is there any harm in taking an antibiotic on and off regularly to prevent infection, easily avoided by safe sex practices?

Antibiotics can cause damage to one’s G.I. tract altering the healthy bacteria and negatively affecting digestion and immune system health. Additionally, using antibiotics on and off can cause AMR. What is AMR? Simply put, AMR creates costly, complex global health problems. AMR is the ability of a microorganism, such as a bacteria, virus, parasite, or fungus, to develop defenses against medications and other products. Resistant infections contribute to over 35,000 deaths annually, according to the U.S. Food and Drug Administration (FDA). Our duty as a population is to minimize the further development of AMR by using antibiotics and other related drugs in a smart, safe, and appropriate fashion.

Doxycycline side effects and drug interactions

While we worry about the big picture and the development of AMR using doxycycline, there are other considerations for antibiotic use. Medications recommended for treatment or PEP to prevent STIs can have side effects.

Common side effects of doxycycline include:

G.I. Upset (vomiting, diarrhea, upset stomach).

Increased skin sensitivity to light (potential for actual damage from the sun).

Vaginal yeast infection.

Dysbiosis (gut bacteria may get out of whack) – Consider taking it with a probiotic.

Less common though more serious side effects we can see include bleeding or bruising, liver disease, esophagus irritation, or allergic reactions, including life-threatening reactions.

Furthermore, doxycycline may interact with other medications, supplements, or vitamins you may be taking. Ensure you inform any physician prescribing this type of drug of all medications and supplements you take. Finally, like most antibiotics, birth control becomes much less effective and cannot be relied upon while on this medication. Thus, additional forms of birth control should be used while taking the drug.

Is doxycycline PEP the answer?

Could doxycycline PEP be an answer to lessen STI risk for select at-risk populations (MSM)? Yes, it may be a tool in our wheelhouse in the future, but cannot take the place of safe sex practices, the first line of defense against STIs. We can’t hope to extend a similar approach to the general public and not develop negative consequences such as AMR and an inability to treat other illnesses for entire populations, not just a subset of a community.

Right now, the public health recommendations for abstinence and additional preventive measures to prevent the transmission of STIs still stand. Counseling, abstinence practices, and other measures should be the first line regardless of subsequent findings in future and ongoing studies.

We must minimize the risk of AMR developing doxycycline and related drugs to ensure that we can treat a variety of infectious diseases globally and across species. We must pursue education across all populations, so individuals minimize harmful behaviors leading to STI risk. Still, research should continue to help identify ways in which doxycycline PEP could be useful in the future.