Ever since the HIV drug emtricitabine/tenofovir disoproxil fumarate (Truvada) was approved as pre-exposure prophylaxis (PrEP), it has been celebrated by those who see it as a powerful HIV prevention tool and condemned by those who argue it encourages condomless sex and fuels sexually transmitted infections (STIs).
Now, a new study in JAMA: Journal of the American Medical Association finds that PrEP use in gay and bisexual men is indeed associated with an uptick in STIs. The study, which was led by researchers at the Burnet Institute in Melbourne, Australia, found that while chlamydia, gonorrhea, and syphilis rates increased among gay and bisexual men taking PrEP, a small group of men accounted for the vast majority of STIs.
On the surface, the new data seem to be bad news for PrEP, which had previously been correlated with higher rates of STIs, but never definitively so. However, an accompanying JAMA editorial argues that the results should not deter clinicians from prescribing PrEP for patients who are most at risk for HIV.
"This does not shed negative light on PrEP at all," said the editorial's lead author, Monica Gandhi, M.D., M.P.H., with the University of California, San Francisco. Instead, Gandhi argues that providers should use PrEP as an opportunity to bolster STI screenings and tackle multiple epidemics simultaneously.
"I don't think this is bad news -- I think it's challenging news," said Jeanne M. Marrazzo, M.D., M.P.H., with University of Alabama at Birmingham. PrEP is part of the "spectrum of health," Marrazzo said. "Unfortunately, the STDs just happen to be along for the ride."
The Australian PrEPX study was an open-label intervention study that tapped into the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) clinic network, enrolling 4,275 participants over two years. Of those, 2,981 had at least one follow-up visit and were monitored until April 2018 across five ACCESS clinics.
Participants received PrEP upon enrollment, accompanied by quarterly HIV and STI testing and clinical monitoring, in accordance with generally accepted PrEP practice guidelines. The men who participated overwhelmingly identified as gay or bisexual (98.5%) and were all relatively young, with a median age of 34 years old. Of the 2,981 who had initially participated at the five ACCESS clinics, 89 withdrew from the study.
After an average follow-up period of just over one year, 48% of study participants were diagnosed with at least one STI (1,434 chlamydia, 1,242 gonorrhea, 252 syphilis). Some participants were diagnosed with more than one STI, for a total of 2,928 STIs detected over the course of the study.
However, a relatively small group of 736 participants -- or about 25% of the overall sample -- accounted for 76% of all the STIs identified during the study.
To Gandhi, this finding makes intuitive sense. "In any epidemic," she said, "there are sometimes groups [that] contribute more to the spread of sexually transmitted infections. That group can be targeted for interventions."
The researchers at the Burnet Institute further crunched the data to understand more about the STI patterns in their cohort. They were able to include just over 2,000 participants in a multivariable analysis to identify risk factors that could have predicted greater STI risk. Ultimately, factors that predicted greater STI risk were younger age, greater number of sexual partners, and group sex. Notably, condom use was not associated with lower STI risk.
The researchers further analyzed a subgroup of 1,378 participants who had records of STI testing data prior to starting PrEP. With these data, they were able to compare the rate of STIs in men before and after initiating PrEP and adjusted their calculations to account for STI testing frequency -- a feature that sets this study apart from prior PrEP/STI studies, according to Marrazzo.
The Melbourne research team found that STI incidence increased from just under 70 cases per 100 person-years to just over 98 cases per 100 person-years (incidence rate ratio [IRR], 1.41 [95%CI, 1.29-1.56]). When the study authors adjusted their calculation to account for STI testing frequency, they still found that the increased incidence of STIs after starting PrEP was significant (adjusted IRR, 1.12 [95%CI, 1.02-1.23]).
The implications of this research are likely to be hotly debated in the HIV prevention community, part of which has long sought to encourage condom use as one of the most reliable ways to prevent HIV and other STIs, despite PrEP.
One of the most challenging implications of the research, according to Marrazzo, is that it shows we still don't have an effective way to prevent STIs other than barrier protection.
"Clearly, [barrier protection] is not acceptable to some people. We really need other methods to prevent STDs, and that probably means vaccines," Marrazzo said.
"PrEP, in my opinion, is a wonderful biomedical prevention tool," Gandhi said. "In the context of curbing that epidemic, [it means] people will likely have more condomless sex, and that is absolutely OK."
Gandhi pointed out that although there are no vaccines to prevent STIs like syphilis and chlamydia, effective screening tools and treatments do exist. As it stands, the Centers for Disease Control and Prevention (CDC) recommends that people taking PrEP get screened for STIs once every three to six months even if they don't have symptoms.
Instead of curtailing PrEP prescriptions, Gandhi argues that the new JAMA study shows that the health care system should be doing a better job of offering STI screening in addition to effective HIV prevention tools.
"We need to screen more frequently for STIs," Gandhi said. "The STI and HIV epidemics -- they can inform each other."
Still, Gandhi worries that some care providers may be dissuaded from prescribing PrEP because of its now well-established link to STIs. There is already evidence that some clinicians are reluctant to prescribe it to the patients who need it the most -- namely, black men who have sex with men (MSM).
"Offering PrEP to patients and preventing STIs should not be viewed as a trade-off," Gandhi and her co-authors write.