In the United States, gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV, with 66% of all HIV diagnoses occurring among MSM in 2017.1 HIV pre-exposure prophylaxis (PrEP) is an effective strategy for preventing new HIV infections and is supported in the US Ending the HIV Epidemic plan.2–4 Accordingly, there have been increasing efforts to improve PrEP uptake among MSM. Yet, as other sexually transmitted infections (STIs) continue to increase in the United States, public health researchers debate whether increasing use of PrEP for HIV may further contribute to increasing bacterial STIs.5,6
Previous research on PrEP and STIs has suggested that MSM on PrEP may engage in greater sexual risk behaviors after starting PrEP (ie, risk compensation).5,7 Thus, although PrEP would lower the probability of acquiring HIV, risk compensation could increase the probability of acquiring another STI. An early meta-analysis in 2016 examined STI incidence rates in 18 cohort studies and found that MSM using PrEP were 25 times more likely to acquire gonorrhea, 11 times more likely to acquire chlamydia, and 45 times more likely to acquire syphilis than MSM not using PrEP.8 A 2018 meta-analysis of 8 observational studies and clinical trials found that PrEP was associated with a 24% increase in any STI, and a 2019 study of longitudinal STI clinic data of US MSM found higher incidence rates of STIs and shorter time to first symptomatic STI among PrEP users, both suggesting a temporal relationship between PrEP use and STI incidence.7,9 Yet, more frequent STI screening for individuals at high risk and on PrEP could increase STI detection as a result of testing practices rather than risk compensation. Modeling research examining the “counteracting phenomena” of changes in risk behavior and STI screening in the context of PrEP demonstrated that at 40% PrEP coverage, 40% risk compensation, and STI screening and treatment every 6 months after initiating PrEP, incidence of gonorrhea and chlamydia could decrease by 42% and 40%, respectively, over a 10-year period.10 This research suggested that PrEP could reduce STI incidence through more frequent STI testing and treatment.10
The described studies were important for examining a temporal relationship between PrEP use and STIs. Still, many were conducted in the context of routine, anticipated follow-up visits that included STI testing and may have been comprised of MSM who were more likely to seek care in clinical settings or be prescribed PrEP because of a higher STI risk at the baseline. National-level, population-based studies of this question could supplement existing literature and help to inform on possible associations and their magnitude for MSM. We sought to evaluate associations between PrEP use and STI prevalence among a multisite sample of non-HIV-positive MSM who participated in National HIV Behavioral Surveillance (NHBS) and completed extragenital STI testing in nonclinical settings as a part of NHBS.
NHBS collects cross-sectional data on HIV prevalence, risk behaviors, and use of prevention services among the following 3 key populations: MSM, persons who inject drugs, and heterosexually active persons at increased risk for HIV infection.11 NHBS sampling procedures have been previously summarized.12 In 2017, venue-based, time-space sampling was used to recruit MSM, and eligible participants were offered a behavioral survey and HIV testing. NHBS eligibility criteria included being male sex at birth, self-identifying as male, ever having sex with another man, being 18 years of age or older, currently residing in a participating metropolitan statistical area, not having previously participated in NHBS during that year's survey, and being able to complete the survey in English or Spanish. NHBS activities were approved by local institutional review boards in participating cities.
In 2017 NHBS, 5 US cities (San Francisco, CA; Houston, TX; Miami, FL; New York City, NY; and Washington, DC) also offered MSM participants STI testing using pharyngeal and rectal self-collected swabs for testing to detect gonorrhea and chlamydia. Nucleic acid amplification tests were performed on specimens using the Aptima Combo 2 assay for Neisseria gonorrhoeae/Chlamydia trachomatis (GC/CT) with the Panther system (Hologic, San Diego, CA) by the Centers for Disease Control and Prevention's (CDC) Laboratory Reference and Research Branch in the Division of STD Prevention (4 cities) and the San Francisco Department of Public Health Laboratory (San Francisco). Additional details on NHBS STI testing in 2017 have been previously published.13
Our analysis examined the associations between PrEP use in the previous 12 months and biologically detected STI at the time of interview, including any STI [ie, either STI (gonorrhea and/or chlamydia) at either anatomic site (pharyngeal and/or rectal)], rectal chlamydia, rectal gonorrhea, pharyngeal chlamydia, and pharyngeal gonorrhea. To provide context and interpretation of these results, we also evaluated associations between PrEP use and (1) self-reported STI diagnoses by a health care provider in the previous 12 months (any, chlamydia, gonorrhea, and syphilis), (2) self-reported STI testing in the previous 12 months, (3) self-reported condomless anal sex with a male partner at last sex, and (4) self-report of 10 or more male sex partners in the previous 12 months. NHBS participants in the 5 cities were eligible for this analysis if they reported having at least one male sex partner in the previous 12 months, reported being non‐HIV-positive (ie, HIV-negative, never tested for HIV, or tested for HIV but never obtained or did not know the test result), consented to STI testing, and had valid STI test results for pharyngeal and rectal gonorrhea and chlamydia. Log-linked Poisson regression models with robust standard errors were used to obtain prevalence ratios (PR) and 95% confidence intervals (CI), and P values were calculated using score tests. All models included city as a covariate and accounted for clustering by venue recruitment event. Our fully adjusted models used to obtain adjusted prevalence ratios (aPR) further controlled for age, race/ethnicity, income, and health insurance, in addition to city. All analyses were conducted in SAS 9.4 (SAS Institute Inc., Cary, NC).
In the 5 cities, there were 1922 eligible, sexually active MSM participants who consented to the NHBS survey, provided complete, valid survey responses, reported being non-HIV-positive, and provided information on PrEP use in the past 12 months. Of these, 1627 (84.7%) consented to STI testing, had valid pharyngeal and rectal gonorrhea and chlamydia test results, and were included in this analysis. Key characteristics of the sample overall and by PrEP use are described in Table 1. A third of MSM were aged 18–29 years (39.2%), and most MSM were White or Hispanic (35.3% and 36.0%, respectively). One-third (32.5%) had an income greater than $75,000 per year, and three-fourths (77.8%) had some form of health insurance. Our sample was evenly distributed across the 5 cities. Overall, 29.6% (481/1627) of participants used PrEP in the past 12 months, and PrEP use ranged from 11.3% (31/273) in Miami to 49.4% (154/312) in San Francisco. Thus, in our sample a third of PrEP users were from San Francisco (32.0%), followed by Washington DC (24.1%) and New York City (23.3%).
TABLE 1. -
Selected Sample Characteristics by PrEP Use in the Past 12 Months Among MSM—NHBS, 5 US Cities, 2017
||Used PrEP in Past Year
||Did Not Use PrEP in Past Year
|n (col %)
||n (col %)
||N (col %)
| Black/African American
| Other/Multiple races
| $75,000 or more
| Houston, TX
| Miami, FL
| New York City, NY
| San Francisco, CA
| Washington, DC
*Hispanics/Latinos can be of any race. Black/African American, White, and Other/Multiple races are all non-Hispanic.
†Numbers may not sum to total due to missing values.
PrEP, HIV pre-exposure prophylaxis; MSM, men who have sex with men; NHBS, National HIV Behavioral Surveillance.
In our main analysis, we found that PrEP use in the past 12 months was significantly associated with having any biologically detected STI at the time of interview (14.6% vs. 12.0%, PR = 1.4, 95% CI: 1.04 to 1.9); this finding was largely driven by differences in prevalence of rectal chlamydia (8.7% vs. 6.0%, PR = 1.6, 95% CI: 1.1 to 2.3) (Table 2). PrEP use was not associated with having biologically detected pharyngeal chlamydia (1.2% vs. 1.4%, PR = 1.2, 95% CI: 0.4 to 3.2), pharyngeal gonorrhea (4.8% vs. 4.5%, PR = 1.2, 95% CI: 0.7 to 2.0), or rectal gonorrhea (2.9% vs. 3.9%, PR = 0.9, 95% CI: 0.5 to 1.8). However, PrEP use was significantly associated with having self-reported any STI diagnosis in the 12 months year (PR = 3.2, 95% CI: 2.6 to 4.0), such as chlamydia (PR = 4.0, 95% CI: 2.9 to 5.5), gonorrhea (PR = 4.1, 95% CI: 3.1 to 5.4), or syphilis (PR = 2.9, 95% CI: 1.9 to 4.4) (Table 2). PrEP use was also significantly associated with receiving STI testing in the past 12 months (PR = 1.7, 95% CI: 1.6 to 1.8), having condomless anal sex with a male partner at last sex (PR = 1.5, 95% CI: 1.4 to 1.7), and reporting 10 or more male sex partners in the past 12 months (PR = 2.0, 95% CI: 1.7 to 2.2).
TABLE 2. -
Detected STI and STI-related Outcomes by PrEP Use Among MSM—NHBS, 5 US Cities, 2017
||Used PrEP in Past yr
||Did Not Use PrEP in Past yr
||PR* (95% CI)
||aPR† (95% CI)
|n (col %)
||n (col %)
|Biologically detected outcomes‡
| Detected any STI
||1.4 (1.04, 1.9)
||1.5 (1.1, 2.0)
| Detected rectal chlamydia
||1.6 (1.1, 2.3)
||1.6 (1.1, 2.4)
| Detected rectal gonorrhea
||0.9 (0.5, 1.8)
||0.9 (0.4, 1.7)
| Detected pharyngeal chlamydia
||1.2 (0.4, 3.2)
||1.1 (0.4, 3.1)
| Detected pharyngeal gonorrhea
||1.2 (0.7, 2.0)
||1.3 (0.7, 2.2)
| Self-reported any STI, past 12 mo§
||3.2 (2.6, 4.0)
||3.2 (2.6, 4.0)
| Self-reported chlamydia, past 12 mo§
||4.0 (2.9, 5.5)
||3.8 (2.7, 5.4)
| Self-reported gonorrhea, past 12 mo
||4.1 (3.1, 5.4)
||4.0 (3.0, 5.3)
| Self-reported syphilis, past 12 mo§
||2.9 (1.9, 4.4)
||3.6 (2.3, 5.5)
| Self-reported STI testing, past 12 mo§
||1.7 (1.6, 1.8)
||1.6 (1.5, 1.7)
| Self-reported CAS with male partner, at last sex‖
||1.5 (1.4, 1.7)
||1.4 (1.3, 1.6)
| Self-reported ≥10 male sex partners, past 12 mo
||2.0 (1.7, 2.2)
||2.0 (1.7, 2.3)
*Models accounted for clustering by venue recruitment event and adjusted for city.
†Models accounted for clustering by venue recruitment event and adjusted for city, age, race, income, and health insurance.
‡Based on biological STI testing at the time of NHBS interview.
§A few participants had missing values for self-reported outcomes (self-reported any STI: 1 missing; self-reported chlamydia: 2 missing; self-reported syphilis: 2 missing; and STI testing: 6 missing). Therefore, these were not included in calculation of percentage.
‖Among those whose last sex partner was male.
CAS, condomless anal sex; STI, sexually transmitted infections; PrEP, HIV pre-exposure prophylaxis; MSM, men who have sex with men; NHBS, National HIV Behavioral Surveillance; yr, year; mo, months.
In the fully adjusted models, the significant association between PrEP use and any biologically detected STI persisted (aPR = 1.5, 95% CI: 1.1 to 2.0). The association specifically with rectal chlamydia was the highest in magnitude (aPR = 1.6, 95% CI: 1.1 to 2.4). Associations between PrEP and pharyngeal chlamydia (aPR = 1.1, 95% CI: 0.4 to 3.1), pharyngeal gonorrhea (aPR = 1.3, 95% CI: 0.7 to 2.2), and rectal gonorrhea (aPR = 0.9, 95% CI: 0.4 to 1.7) remained nonsignificant.
Overall, our study found a high prevalence of extragenital gonorrhea and chlamydia for both MSM on PrEP and those not on PrEP in the past year. MSM on PrEP were more likely to have any of the tested STIs overall, largely driven by differences in rectal chlamydia. Self-reported STI diagnoses in the past year, STI testing in the past year, having condomless anal sex with a male partner at last sex, and having 10 or more male sex partners in the past year were also significantly higher among MSM using PrEP compared to nonusers.
The association we found between PrEP use and having any of the tested STIs suggests that MSM on PrEP may have a higher STI prevalence at the population level when tested in nonclinical settings. Yet, we also found heterogeneity by pathogen and anatomic site. PrEP users were 60% more likely to have rectal chlamydia than nonusers, whereas there were no differences in pharyngeal chlamydia, pharyngeal gonorrhea, or rectal gonorrhea. Although our study is based on cross-sectional data, which limits conclusions about causality, our results do generate a few hypotheses regarding possible explanatory factors.
First, our findings could suggest that being on PrEP may lead to a greater risk for rectal STI but not pharyngeal STI. This may be particularly plausible because PrEP reduces the probability of HIV transmission, and the risk of HIV transmission through oral sex is low.14 Thus, condomless oral sex that could result in pharyngeal STIs would unlikely be modified by using PrEP. Under this hypothesis, we would expect condomless anal sex to be modified by PrEP use, given per-act HIV transmission risk is higher through anal sex and PrEP prevents HIV transmission by up to 99% among MSM.14,15 Although we could not report on changes in condomless anal sex before and after PrEP initiation, we did find that condomless anal sex with a male partner at last sex was higher among PrEP users (62.2% vs. 43.4%). It is possible that this difference was driven by increases in condomless anal sex after PrEP initiation, yet it is also possible that those who generally engaged in condomless anal sex were more likely to take PrEP and continued to engage in condomless anal sex near the time of interview. Still, PrEP users did report a greater recent sexual risk behavior and had a higher prevalence of rectal chlamydia. We did not, however, see differences in rectal gonorrhea by PrEP status. One explanation could be that our sample size and the prevalence of rectal gonorrhea were too small to detect differences. Similarly, because we only conducted testing in 5 US cities, it is possible that these cities did not cover geographic regions with substantial PrEP use or a large burden of rectal gonorrhea cases that would allow for sufficient power to detect differences in rectal gonorrhea by PrEP status. We examined post hoc whether the null magnitude of the rectal gonorrhea measure of association could alternatively be explained by city-specific differences; we tested for interaction by city, but it was not significant, and there was large variance around the city-specific associations. Increasing statistical power and including additional cities in geographic regions with a higher rectal gonorrhea burden could be useful to better elucidate the association between PrEP and rectal gonorrhea specifically. Nevertheless, a recent cohort study of Australian MSM who had never taken PrEP demonstrated a 21% increase in any STI and a 38% increase in chlamydia incidence after initiating PrEP.16 Furthermore, a meta-analysis examining PrEP and STI incidence found a 59% increase in rectal chlamydia incidence among MSM PrEP users, an association very close in magnitude to our results.7 Although distinct study designs and populations, our results of higher prevalence of rectal chlamydia among PrEP users support similar conclusions as earlier evidence and warrant continued investigation of rectal STI incidence among MSM using PrEP.
A second hypothesis is that STI incidence may be higher among PrEP users, yet, the duration of infection may be shorter for those on PrEP due to more frequent STI testing and treatment as recommended for PrEP users.17,18 The dynamics between possible higher incidence and shorter duration of infection could result in equal prevalences of STI between PrEP users and nonusers as we observed for pharyngeal gonorrhea and chlamydia and rectal gonorrhea. Rectal chlamydia could have been higher in PrEP users in our study simply due to a higher background prevalence and transmissibility. This potential explanation for our results would support previous modeling research, suggesting that more frequent STI screening and treatment for MSM on PrEP could outweigh increases in risk compensation and could decrease STI incidence in the long-term.10 In our study, we did see greater STI testing in the past year among PrEP users (91.5% vs. 51.8%), although testing may have occurred before or as part of PrEP initiation. Measuring well-defined, time-specific constructs including recent condomless anal sex, number of partners, and frequency of STI testing in studies and surveillance of MSM will continue to be important for understanding factors driving STI incidence trends in an era of increasing PrEP use. Future studies that seek to evaluate the association of PrEP and STIs should consider assessing differences by bacteria and anatomic site, powering the study for rectal gonorrhea outcomes, and further examining the association between PrEP use and rectal chlamydia to better identify mechanisms that could explain the higher prevalence we and others have observed among PrEP users.
Our findings of higher self-reported STI diagnoses, STI testing, and number of partners among PrEP users were consistent with expected associations because many of these factors contribute to CDC-based indications for PrEP and use past-12-month time frames.18 Nevertheless, a high proportion of MSM using PrEP reported having 10 or more male sex partners in the past year and having condomless anal sex with a male partner at last sex, indicating that this group of MSM are still at high risk for other STIs and should continue to be encouraged to use condoms consistently and correctly and offered STI testing on a regular basis.1,18 Nearly all PrEP users had at least one STI test in the past year compared to half of MSM not on PrEP; however, we did not have data on STI testing at more frequent intervals or before and after PrEP initiation to determine whether MSM currently on PrEP are being adequately screened for STIs. The CDC guidelines currently recommend at least annual STI testing for all MSM regardless of PrEP use and every 3 months for those using PrEP.17,18 It will be important to continue to reduce existing gaps in STI testing among MSM including reaching the approximately one in 12 MSM on PrEP and one in 2 MSM not on PrEP that have not received any STI testing in the past year. Furthermore, ensuring regular, frequent STI testing for MSM may provide a valuable avenue for MSM and their health care providers to continually engage in conversations about their sexual health and PrEP.
There are several limitations to our study. First, our data are cross-sectional; therefore, we cannot make conclusions about the timing of PrEP use in the past 12 months and how that may correspond with STI diagnoses in the past 12 months or time of initial biological STI infection. We made a reasonable assumption that PrEP use in the past 12 months preceded the biologic STI testing at the time of interview, yet we recognize that PrEP use in the past 12 months may not accurately capture current PrEP use. Furthermore, our past-12-month outcomes for STI testing and risk behaviors could not distinguish between pre-PrEP and post-PrEP behaviors, and thus, we were not able to control for a baseline risk or testing behaviors before PrEP use. We aimed to use more time-specific measures for risk behaviors when possible, such as condomless anal sex with a male partner at last sex, when examining potential risk compensation. Nevertheless, cross-sectional studies are not designed to capture temporal relationships, and thus, we only discuss prevalence of PrEP and STIs at a given point in time in this population. Second, we only conducted extragenital testing for gonorrhea and chlamydia in this study; our STI prevalence outcomes do not include genital infections that contribute to overall STI prevalence in the population. However, some research has suggested that pharyngeal and rectal testing may miss only a small proportion of urogenital-only infections in MSM.19 Third, MSM were recruited using venue-based sampling; therefore, results may not be generalizable to non-venue-attending MSM. Finally, our self-reported measures are subject to potential social desirability or recall biases that may have underestimated behavioral risks and overestimated testing outcomes.
PrEP use in the past year was associated with having any of the tested STIs overall, and specifically rectal chlamydia. Prevalences of pharyngeal gonorrhea and chlamydia and rectal gonorrhea were similar between MSM on PrEP and those not on PrEP. Future studies should examine hypotheses for a possible increased risk of rectal chlamydia or other rectal STIs for MSM on PrEP. Because STI prevalences were high for both PrEP users and nonusers, our findings support consistent and correct condom use to prevent STI and frequent STI testing for MSM to identify infections early and initiate treatment. This includes STI testing every 3 months for MSM on PrEP and at least annually for sexually active MSM regardless of PrEP use. Furthermore, testing at all anatomical sites of potential STI exposure is important to detect and treat STI, including those at extragenital sites.
NHBS STI Study Group: Houston: Zaida Lopez and Paige Padgett; Miami: David Forrest and Willie Nixon; New York City: Sidney Carrillo and Alexis Rivera; San Francisco: Theresa Ick; and Washington, DC: Irene Kuo and Anya Agopian
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