The rate of sexually transmitted infections (STIs) is high among gay and bisexual men starting pre-exposure prophylaxis (PrEP), offering opportunities for stepped-up testing and treatment, according to an Australian study published in the Journal of the American Medical Association.

In this study of nearly 3,000 sexually active men who have sex with men, just under half were diagnosed with a bacterial STI—chlamydia, gonorrhea or syphilis—during the first year on PrEP. However, a quarter of the participants accounted for three quarters of new STIs, pointing to a subgroup of men who could potentially benefit from more intensive prevention efforts.

“Findings suggested that STI prevention campaigns should not focus solely on condom use but also on reducing the time to STI diagnosis and treatment by promoting easy access to frequent testing,” lead researcher Michael Traeger, MSc, of the Burnet Institute in Melbourne, and colleagues wrote.

Taking Truvada (tenofovir disoproxil fumarate/emtricitabine) daily or on a fixed schedule before and after sex dramatically reduces the risk of acquiring HIV. But these antiretrovirals do not prevent other STIs. Some experts have expressed concern that if people reduce their condom use after starting PrEP, this could lead to a rise in STIs. On the other hand, the frequent STI testing recommended while on PrEP could lead to earlier detection and treatment, which would interrupt STI transmission. Prior studies of the link between PrEP and changes in behavior, including condom use, have yielded mixed results.

Traeger’s team conducted the Pre-exposure Prophylaxis Expanded (PrEPX) implementation study to learn more about STI incidence and behavioral risk among gay and bi men who use PrEP and to look at changes in STI rates after starting PrEP.

This analysis included 2,981 participants who enrolled at four primary care or sexual health clinics and one community-based HIV testing site in Victoria, Australia, between July 2016 and March 2018.

The median age was 34 years and almost all identified as gay or bisexual men; less than 2% identified as transgender or nonbinary. Eligible participants were predicted to have ongoing HIV risk over the next three months based on their self-reported behavior. Just under half reported recent condomless receptive anal sex with an HIV-positive or unknown-status partner, a quarter were diagnosed with an STI at or shortly before enrollment, 12% reported a history of injection drug use, one in four had ever used post-exposure prophylaxis (PEP) and 29% had previously used PrEP.

At enrollment, participants started taking daily Truvada for PrEP. HIV and STI testing, clinical monitoring and a behavioral survey were done every three months. Follow-up continued through the end of April 2018. Study findings were first presented at the International AIDS Conference last summer in Amsterdam.

During an average follow-up period of about a year, 48% of participants were diagnosed with an STI: 1,434 with chlamydia, 1,242 with gonorrhea and 252 with syphilis. Rectal infections were most common (57%), followed by throat infections (24%) and urethral infections (19%). A quarter of participants were diagnosed with two or more STIs, 13% had three or more and 3% had five or more. The overall STI incidence rate was high, at 91.9 per 100 person-years of follow-up.

But STIs did not occur uniformly across the entire study population. Just over half of participants had no STIs. The researchers found that 25% of participants accounted for 76% of all diagnosed STIs. More than half of all diagnoses were in people who had three or more STIs during follow-up, and 19% were in those with five or more STIs.

Among the 2,058 participants with complete data available, younger age, having more sex partners and engaging in group sex were associated with greater STI risk in a multivariate analysis that took multiple factors into account. Of note, condom use was not independently associated with a lower STI risk.

Looking at 1,378 people with pre-enrollment testing data, the rate of STI diagnosis rose after entering the study, from 69.5 to 98.4 per 100 person-years of follow-up. After adjusting for the substantially higher frequency of testing during the study, STI incidence still rose by 12%—a statistically significant increase that probably was not driven by chance alone. Zeroing in on those who started PrEP for the first time during the study, STI incidence rose from 55.1 to 94.2 per 100 person-years, an adjusted increase of 21%.

“Among gay and bisexual men using PrEP, STIs were highly concentrated among a subset, and receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with pre-enrollment,” the study authors concluded. “These findings highlight the importance of frequent STI testing among gay and bisexual men using PrEP.”

Because the study did not include a control group that did not receive PrEP, the results “could not directly imply that PrEP initiation per se caused the observed increase in STI risk,” the researchers cautioned. “The lack of association with condoms and clustering of STIs in a small group of participants suggested that commencing PrEP may be associated with unknown or unmeasured factors that drive STI risk, such as changes in the size and constituents of sexual networks or other unmeasured sexual behaviors.”

Monica Gandhi, MD, MPH, of the University of California San Francisco, and Matthew Spinelli, MD, and Kenneth Mayer, MD, of the Fenway Institute in Boston, offered further caveats in an accompanying editorial.


Acknowledging that the HIV and STI epidemics, “have always been and will always be intertwined,” the authors state that “[c]oncerns about behavioral change after starting PrEP should not decrease the willingness of clinicians to offer PrEP.”

Because most STIs are asymptomatic at early stages, regular testing can catch these infections before people are aware they have them. Although behavior change after starting PrEP may lead to a short-term rise in STIs, Ghandi and coauthors note that a mathematical modeling study suggests that more frequent testing while on PrEP could lead to increased detection and early treatment of STIs, which could eventually decrease the overall STI burden even if people using PrEP have more condomless sex.

“Offering PrEP to patients and preventing STIs should not be viewed as a trade-off. The HIV and STI epidemics comprise a syndemic that is now addressable,” Ghandi and colleagues wrote. “The onus is now on health care systems and clinicians to promote and implement the comprehensive sexual health services that are needed to achieve the elimination of HIV transmissions and the end of the current STI epidemic.”

The current Centers for Disease Control and Prevention PrEP guidelines recommend that gay men at risk should be screened for STIs, along with HIV testing, every three months while taking PrEP. The PrEPX findings suggest that frequent screening is most urgent for a subgroup of men with specific risk factors, while other men at less risk may do well with less frequent STI testing.