Increased Risk of Sexually Transmitted Infections in Men Who Have Sex With Men Taking Preexposure Prophylaxis: A Meta-analysis : Sexually Transmitted Diseases

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Increased Risk of Sexually Transmitted Infections in Men Who Have Sex With Men Taking Preexposure Prophylaxis: A Meta-analysis

Zhou, Qian PhD∗,†; Liu, Jingwei PhD∗,†; Li, Hao PhD∗,†; Han, Yan PhD∗,†; Yin, Yueping PhD∗,†

Author Information
Sexually Transmitted Diseases 49(11):p 733-739, November 2022. | DOI: 10.1097/OLQ.0000000000001698
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Up to 2 million new HIV infections occur yearly worldwide. Because there is no effective vaccine to prevent HIV transmission, behavioral and biomedical HIV prevention strategies are needed to reduce HIV acquisition.1 Preexposure prophylaxis (PrEP) is an evidence-based way to prevent HIV infections for HIV-uninfected patients using antiretroviral medications. As a priority population for HIV prevention, there have been several large trials demonstrating the safety and efficacy of PrEP in reducing HIV transmission among men who have sex with men (MSM) who are at high risk for HIV transmission.2 According to the results of a meta-analysis, the rate of HIV acquisition was reduced by 86% in MSM taking PrEP with high adherence.3

Although PrEP shows high efficacy in decreasing HIV incidence among these population, concerns remain that widespread PrEP uptake may result in behavioral change that leads to increases in sexually transmitted infections (STIs); one of the main reasons for this population taking PrEP is that it can effectively reduce their risk for acquiring an HIV infection without using condoms.3 Currently, increased incidence of chlamydia infection, gonorrhea, and syphilis in MSM has been reported in many countries.4 Also, the decreasing antibiotic susceptibility of Neisseria gonorrhoeae and the rise of more severe syphilis complications complicated the treatment and prognosis of STIs in high-risk populations for HIV/AIDS.5,6

In this study, we performed a meta-analysis of the incidence density of STIs during the period of taking PrEP versus before taking PrEP in MSM, with the aim of investigating the possible increased risk of STIs among MSM taking PrEP, to provide data support for the STI prevention in PrEP participants.

METHODS

This meta-analysis was registered through PROSPERO (registration number CRD42022335974).

Search Strategy and Study Selection

The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.7 Two researchers (Q.Z. and J.L.) independently searched PubMed, EMBASE, Web of Science databases, China National Knowledge Infrastructure, and Wanfang Database from January 2012 (the year in which PrEP became available) to April 2022 using the terms ((chlamydia OR sexually) AND (prophy*) AND (HIV)) to identify relevant studies. Endnote X20 (Thomson Reuters, Toronto, Ontario, Canada) was used to manage the retrieved records, and RevMan 5.2 (RevMan 2014) was used to generate pictures of the flow diagram.

Two independent reviewers removed duplicates and screened literature based on the title and abstract, and then assessed the full texts of the remaining records. The studies for the meta-analysis were included if they fulfilled the following eligibility criteria: (1) published in English and Chinese, (2) focused on MSM, (3) used the PrEP intervention, and (4) reported the incidence density of STIs during PrEP period or before taking PrEP.

Data Extraction

We used a standardized form to summarize the data collected in the literature included. The data extracted included the following information: (1) title, first author, publication year, and research type; (2) study population, study location, and median age of the study population; (3) incidence data of syphilis, gonorrhea, and chlamydia infection; and (4) the population–time of observation after the intervention was conducted. Some of the data were in the supplementary files or discussion section, and we extracted this part of the data as well.

Assessment of the Quality

The quality was assessed according to the type of studies included. The quality of the nonrandomized studies was assessed by using the Methodological Index for Non-Randomized Studies (MINORS) scale.8 The MINORS scale for single-arm studies consisted of 8 items, including (1) a clearly stated aim, (2) inclusion of consecutive patients, (3) prospective collection of data, (4) end points appropriate to the aim of the study, (5) unbiased assessment of the study end point, (6) follow-up period appropriate to the aim of the study, (7) loss of follow-up less than 5%, and (8) prospective calculation of the study size. The items are scored 0 (not reported), 1 (reported but inadequate), or 2 (reported and adequate). The total score was 16, and trails with MINORS scores >12 were included in the study.9 For case-control studies or cohort studies, the Newcastle-Ottawa Scale (NOS) was used for quality assessment. The NOS tool assessed cohort studies in 3 areas: selection of study groups, comparability of the groups, and ascertainment of the outcome. The total score of NOS was 9 points.10

Meta-analysis

The heterogeneity was evaluated by the Higgins I2 test statistic. If the value of I2 was more than 50%, a random-effects model was applied; otherwise, a fixed-effects model was used. The incidence density was calculated by the number of incidences per 100 person-years (PY) for syphilis, gonorrhea, and chlamydia infection. The 95% confidence intervals (CIs) were determined from the incidences and PY assuming a Poisson distribution. To investigate the source of heterogeneity, subgroup analyses based on the type of research (prospective or retrospective study) and study location (North American or others) were conducted. Furthermore, the publication bias was detected by Egger's publication bias plot, and a P value less than 0.05 indicated a statistically significant publication bias.

RESULT

Literature Collection

A total of 714 records were identified from 3 databases published up to April 2022, of which 562 remained after duplicates had been removed. Of these, 511 were excluded because the title and abstract revealed them to be not related, non-English literature, reviews, books, case reports, and comments. The remaining 51 full-text articles were assessed for eligibility. Twenty-three of these studies did not provide data, and 8 provided only the combined incidence of STIs (Fig. 1). Finally, 20 studies met the inclusion criteria for the final analysis.11–30 From these studies, we extracted 19 groups of incidence data of syphilis, 19 of gonorrhea, and 18 of chlamydia infection during the PrEP period. Five of these studies investigated the incidence data before taking PrEP.22,23,27–29

F1
Figure 1:
Flow diagram for selecting published studies for meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, generated by Review Manager Software (RevMan version 5.3).

Study Characteristics

Data extraction was performed on the 20 included articles, of which 6 were single-arm clinical trials, 9 were cohort studies, 2 were case-control studies, and 3 were retrospective descriptive studies. There were 9 studies from North America and 11 from other locations. A total of 8820 participants were enrolled in these studies, yielding a cumulative 10,563.75 PY of follow-up. The median age of the included population was 30 to 40 years. The characteristics and incidence data of these studies are summarized in Tables 1 and 2.

TABLE 1 - Characteristics of 20 Studies Included in the Meta-analysis
No. First Author Year Type of Study Study Location Participants Mid-Age, y
1 Zeggagh 11 2022 Single-arm clinical Trial France and Canada 429 35
2 Tabatabavakili 12 2022 Retrospective longitudinal cohort study Canada 344 35
3 Saxton 13 2022 Single-arm clinical Trial New Zealand 142 30
4 Mehta 14 2021 Prospective cohort study Kenya 158 33
5 Jongen 15 2021 Prospective cohort study Netherlands 571 39
6 De Baetselier 16 2021 Single-arm clinical Trial Belgium 179 39
7 Chemtob 17 2021 Retrospective cohort study Israeli 757 35
8 Azarnoosh 18 2021 Case-control study Denmark 46 39
9 Ayerdi Aguirrebengoa 19 2021 Retrospective descriptive study Spain 110 34.7
10 Van Praet 20 2020 Single-arm clinical Trial Belgium 131 40
11 Gravett 21 2020 Retrospective descriptive study United States 81 32
12 Traeger 22 2019 Single-arm clinical Trial Australia 2981 34
13 Montaño 23 2019 Retrospective cohort study United States 365 30.6
14 John 24 2019 Retrospective descriptive study United States 104 32
15 Hoornenborg 25 2019 Prospective cohort study Netherlands 367 40
16 Tan 26 2018 Single-arm clinical Trial Canada 52 33
17 Nguyen 27 2018 Prospective cohort study Canada 109 36
18 Beymer 28 2018 Case-control study United States 275 35
19 Mayer 29 2017 Prospective cohort study United States 647 30
20 Marcus 30 2016 Prospective cohort study Canada 972 37.5

TABLE 2 - Incidence Data of 20 Studies Included in the Meta-analysis
Name of the Study Syphilis Chlamydia Infection Gonorrhea
Incidences Population-Time Incidences Population-Time Incidences Population-Time
Zeggagh et al. 11 112 864 275 864 261 864
Tabatabavakili et al. 12 15 282 102 282 139 282
Saxton et al. 13 14 133.25 71 133.25 98 133.25
Mehta et al. 14 39 145
Jongen et al. 15 116 994 519 1058 447 1058
De Baetselier et al. 16 22 268.5 101 268.5 93 268.5
Chemtob et al. 17 51 658.75
Azarnoosh et al. 18 5 23 14 23 14 23
Ayerdi Aguirrebengoa et al. 19 32 208 219 208 155 208
Van Praet et al. 20 19 128.5 38 128.5 45 128.5
Gravett et al. 21 4 78.5 15 78.5 13 78.5
Traeger et al. 22 252 3185 1242 3185 1434 3185
Montaño et al. 23 25 365 135 365 165 365
John et al. 24 3 58.25 13 58.25 10 58.25
Hoornenborg et al. 25 75 681.75 186 681.75 180 681.75
Tan et al. 26 4 48.75 16 48.75 16 48.75
Nguyen et al. 27 16 109 31 109 44 109
Beymer et al. 28 29 164.5 120 167.5 89 167.5
Mayer et al. 29 62 1318 185 1318 241 1318
Marcus et al. 30 56 850 177 850 203 850

Quality Assessment

The results of the quality assessment using the MINORS scale and NOS tool are presented in Tables 3 and 4. The methodological quality for 9 nonrandomized studies scored 12 to 16 using the MINORS scale. For 11 cohort studies and case-control studies, the NOS scores ranged from 7 to 9, which indicated a reliable quality.

TABLE 3 - The Score of 9 Nonrandomized Studies Using the MINORS Scale
No. First Author I II III IV V VI VII VIII Total
1 Zeggagh 11 2 2 2 2 1 2 2 2 15
3 Saxton 13 2 2 2 2 1 2 1 2 14
6 De Baetselier 16 2 2 2 2 2 2 2 2 16
9 Ayerdi Aguirrebengoa 19 2 2 0 2 2 2 2 0 12
10 Van Praet 20 2 2 2 1 2 2 2 2 15
11 Gravett 21 2 2 0 2 2 2 2 0 12
12 Traeger 22 2 2 2 2 2 2 2 2 16
14 John 24 2 2 0 2 2 2 2 0 12
Numbers I to VIII in the heading signified the following: I, a clearly stated aim; II, inclusion of consecutive patients; III, prospective collection of data; IV, end points appropriate to the aim of the study; V, unbiased assessment of the study end point; VI, follow-up period appropriate to the aim of the study; VII, loss of follow-up less than 5%; VIII, prospective calculation of the study size. The items are scored 0 (not reported), 1 (reported but inadequate) or 2 (reported and adequate).

TABLE 4 - The Score of 11 Cohort Studies and Case-Control Studies Using the NOS Tool
No. First Author I II III IV V VI VII VIII Total
2 Tabatabavakili 12 1 1 1 0 2 1 1 1 8
4 Mehta 14 1 1 1 1 2 1 1 1 9
5 Jongen 15 1 1 1 1 2 1 1 1 9
7 Chemtob 17 1 1 1 1 2 0 1 1 8
8 Azarnoosh 18 1 1 1 0 2 1 0 1 7
13 Montaño 23 1 1 1 0 2 1 1 1 8
15 Hoornenborg 25 1 1 1 1 2 1 1 1 9
16 Tan 26 1 1 1 1 2 1 1 0 8
17 Nguyen 27 1 1 1 1 2 0 1 0 7
18 Beymer 28 1 1 0 1 2 1 1 1 8
19 Mayer 29 1 1 1 1 2 1 1 1 9
20 Marcus 30 1 1 1 1 2 0 1 1 8
Numbers I to VIII in the heading signified the following: I, representativeness of the exposed cohort; II, selection of the nonexposed cohort; III, ascertainment of exposure; IV, demonstration that outcome of interest was not present at start of study; V, compare ability of cohorts on the basis of the design or analysis; VI, assessment of outcome; VII, was follow-up long enough for outcomes to occur; VIII, adequacy of follow-up of cohorts (1 point for each item, 2 points for compare ability, 9 points in total).

Meta-analysis

After pooling the incidence density for the 3 pathogens during the PrEP period, the pooled estimate of incidence density of syphilis was 9.53 per 100 PY (95% CI, 8.21–11.06), whereas it was 36.48 per 100 PY (95% CI, 31.47–42.28) for chlamydial infection and 34.79 per 100 PY (95% CI, 29.50–41.02) for gonorrhea (Fig. 2). The pooled estimate of incidence density of syphilis before taking PrEP was 5.95 per 100 PY (95% CI, 4.59–7.71), whereas it was 20.66 per 100 PY (95% CI, 17.44–24.49) for chlamydial infection and 19.52 per 100 PY (95% CI, 16.91–22.53) for gonorrhea. After performing the Wilcoxon rank sum test, the incidence density of 3 STIs during the PrEP period was significantly lower than the value during PrEP (P < 0.05).

F2
Figure 2:
A, Pooled incidence density of syphilis. B, Pooled incidence density of chlamydial infection. C, Pooled incidence density of gonorrhea.

Subgroup Analysis

Subgroup analysis was performed according to prospective or retrospective studies. For prospective studies, syphilis, chlamydial infection, and gonorrhea incidence densities were 9.61, 34.34, and 30.77 per 100 PY, respectively, compared with 9.25, 40.46, and 42.87 per 100 PY for retrospective studies (Fig. 3). Syphilis, chlamydial infection, and gonorrhea incidence densities were 7.50, 30.08, and 28.18 per 100 PY for studies in North America, respectively, and these data were 11.33, 43.82, and 41.91 per 100 PY for studies in other regions (Fig. 4).

F3
Figure 3:
A, Syphilis incidence density by study type subgroup analysis. B, Chlamydial infection incidence density by study type subgroup analysis. C, Gonorrhea incidence density by study type subgroup analysis.
F4
Figure 4:
A, Syphilis incidence density by study location subgroup analysis. B, Chlamydial infection incidence density by study location subgroup analysis. C, Gonorrhea incidence density by study location subgroup analysis.

Publishing Bias

Publication bias testing of the included studies was conducted using Egger's method. Egger's test results (Psyphilis = 0.536 > 0.05; Pchlamydial = 0.235 > 0.05; Pgonorrhea = 0.714 > 0.05) showed no publication bias for any of the 3 pathogens (Fig. 5).

F5
Figure 5:
A, Egger's publication bias plot of syphilis. B, Egger's publication bias plot of chlamydial infection. C, Egger's publication bias plot of gonorrhea.

DISCUSSION

As an effective method to prevent HIV infection in high-risk populations, PrEP is gradually being studied more and more in MSM.31 Meanwhile, for those studies using PrEP, STI testing is required every 3 months for syphilis, chlamydia, and gonorrhea, which provides us with the feasibility to investigate the incidence density of the 3 pathogens.32 Because incidence density measures the occurrence of disease onsets in a population per unit of time of follow-up, it could be a better indicator of the occurrence of STIs in MSM during the PrEP period than prevalence, which referred to all cases in the population at a given time. This meta-analysis aimed to generate estimates for incidence density for 3 STIs among MSM taking PrEP. Pooled data from 20 studies showed that the incidence density of syphilis was 9.53 per 100 PY, whereas it was 36.48 per 100 PY for chlamydial infection and 34.79 per 100 PY for gonorrhea. The combined incidence density of these 3 STIs was 81.07 per 100 PY.

After performing a comparison of the incidence density during the PrEP period with that before taking PrEP, we found that the former was significantly higher than the latter. Comparing the pooled data from MSM using PrEP with other MSM not using PrEP on the incidence of STI in MSM after 2016, for syphilis incidence density, in a Thai study, the incidence density of syphilis in MSM was 4.5 per 100 PY,33 whereas in another Chinese study, the incidence density of syphilis was 5.6 per 100 PY34; the syphilis incidence density in MSM using PrEP in this study was higher than the results in MSM not using PrEP. As for the incidence density of gonorrhea and chlamydia infection, the study showed that the incidence of gonorrhea in MSM was 15.6 to 21.1 per 100 PY, and chlamydia infection was 19.3 to 19.5 per 100 PY.27,35 Some studies provided the combined incidence density of gonorrhea and chlamydia infection of 18.0 to 33.1 per 100 PY,36,37 which was lower than the results of our study. Men who have sex with men taking PrEP have high incidence of STIs, which may be due to these factors: that PrEP helps to reduce the acquisition of HIV may increase more high-risk sexual behaviors in MSM such as multiple sexual partners, the decrease in condom use, and more frequent and more vigorous sexual activity.22,38 Loss to follow-up bias could not be negligible. Moreover, all the studies included in this meta-analysis had a loss of follow-up rate of less than 10%. Those who were knowingly exposed to STIs or symptomatic were more likely to finish follow-up, which would also increase the statistical incidence density of STIs.

The results of subgroups analysis indicated the differences by study type and study location. In the study type subgroup analysis, it was found that the incidence density tended to be lower in prospective studies than in retrospective studies, possibly because of limitations in using data from trials or cohort studies to estimate STI incidence and because some studies were not specifically designed to assess STI incidence.39 In the study location subgroup analysis, incidence density was lower in North America than in other regions, and there may be multiple influences, including changes in sexual behavior among MSM and mobility of the MSM population.40–42

Considering the progressive increase in antibiotic resistance of sexually transmitted disease pathogens and more complex treatment of STIs in recent years, the high incidence of STIs in MSM population taking PrEP is a cause for alarm. As can be surmised from the higher STI incidence results in this study, sustained efforts to control the transmission of STIs among PrEP users and their sexual partners would be meaningful. Examples include education of this population and emphasis on condom use during sexual behavior. Also, as part of the PrEP program, routine testing and comprehensive treatment of STIs (including syphilis, chlamydia infection, and gonorrhea) are highly prevalent among MSM. Further research to evaluate new biomedical strategies also needs to be conducted for the prevention of bacterial STIs, such as antibiotic PrEP and antibiotic use in postexposure prophylaxis.43

Through this meta-analysis and systematic review, we estimated the incidence density of 3 STIs in an MSM population taking PrEP. The high incidence of STIs in the MSM taking PrEP needs to be increasingly appreciated, and the prevention of STIs is valuable among MSM alongside HIV prevention uptake.

REFERENCES

1. Maartens G, Celum C, Lewin SR. HIV infection: Epidemiology, pathogenesis, treatment, and prevention. Lancet 2014; 384:258–271.
2. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363:2587–2599.
3. Murchu EO, Marshall L, Teljeur C, et al. Oral pre-exposure prophylaxis (PrEP) to prevent HIV: A systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations. BMJ Open 2022; 12:e048478.
4. Yeung H, Luk KM, Chen SC, et al. Dermatologic care for lesbian, gay, bisexual, and transgender persons: Epidemiology, screening, and disease prevention. J Am Acad Dermatol 2019; 80:591–602.
5. Costa-Lourenço APRD, Barros dos Santos KT, Moreira BM, et al. Antimicrobial resistance in Neisseria gonorrhoeae: History, molecular mechanisms and epidemiological aspects of an emerging global threat. Braz J Microbiol 2017; 48:617–628.
6. Scott HM, Klausner JD. Sexually transmitted infections and pre-exposure prophylaxis: Challenges and opportunities among men who have sex with men in the US. AIDS Res Ther 2016; 13:5.
7. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Syst Rev 2021; 10:89.
8. Zeng X, Zhang Y, Kwong JS, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: A systematic review. J Evid Based Med 2015; 8:2–10.
9. Slim K, Nini E, Forestier D, et al. Methodological Index for Non-Randomized Studies (MINORS): Development and validation of a new instrument. ANZ J Surg 2003; 73:712–716.
10. Stang A. Critical evaluation of the Newcastle-Ottawa Scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25:603–605.
11. Zeggagh J, Bauer R, Delaugerre C, et al. Incidence and risk factors for recurrent sexually transmitted infections among MSM on HIV pre-exposure prophylaxis. AIDS 2022; 36:1129–1134.
12. Tabatabavakili S, Aleyadeh W, Cerrocchi O, et al. Incidence of hepatitis C virus infections among users of human immunodeficiency virus pre-exposure prophylaxis. Clin Gastroenterol Hepatol 2022; 20:674–681.
13. Saxton PJW, Azariah S, Cavadino A, et al. Adherence, sexual behavior and sexually transmitted infections in a New Zealand prospective PrEP cohort: 12 Months follow-up and ethnic disparities. AIDS Behav 2022; 26:2723–2737.
14. Mehta SD, Okall D, Graham SM, et al. Behavior change and sexually transmitted incidence in relation to PREP use among men who have sex with men in Kenya. AIDS Behav 2021; 25:2219–2229.
15. Jongen VW, Reyniers T, Ypma ZM, et al. Choosing event-driven and daily HIV pre-exposure prophylaxis—Data from two European PrEP demonstration projects among men who have sex with men. J Int AIDS Soc 2021; 24:e25768.
16. De Baetselier I, Reyniers T, Platteau T, et al. Recurrent sexually transmitted infections among a cohort of men who have sex with men using preexposure prophylaxis in Belgium are highly associated with sexualized drug use. Sex Transm Dis 2021; 48:726–732.
17. Chemtob D, Weil C, Hannink Attal J, et al. HIV pre-exposure prophylaxis (PrEP) purchase patterns and STI occurrence among Israeli men: A cohort analysis. PLoS One 2021; 16:e0259168.
18. Azarnoosh M, Johansen IS, Martin-Iguacel R. Incidence of sexually transmitted infections after initiating HIV pre-exposure prophylaxis among MSM in southern Denmark. Am J Mens Health 2021; 15:15579883211018917.
19. Ayerdi Aguirrebengoa O, Vera García M, Arias Ramírez D, et al. Low use of condom and high STI incidence among men who have sex with men in PrEP programs. PLoS One 2021; 16:e0245925.
20. Van Praet JT, Steyaert S, Vandecasteele S, et al. Mycoplasma genitalium acquisition and macrolide resistance after initiation of HIV pre-exposure prophylaxis in men who have sex with men. Sex Transm Infect 2020; 96:396–398.
21. Gravett RM, Westfall AO, Overton ET, et al. Sexually transmitted infections and sexual behaviors of men who have sex with men in an American Deep South PrEP clinic. Int J STD AIDS 2020; 31:127–135.
22. Traeger MW, Cornelisse VJ, Asselin J, et al. Association of HIV preexposure prophylaxis with incidence of sexually transmitted infections among individuals at high risk of HIV infection. JAMA 2019; 321:1380–1390.
23. Montaño MA, Dombrowski JC, Dasgupta S, et al. Differences in sexually transmitted infection risk comparing preexposure prophylaxis users and propensity score matched historical controls in a clinic setting. AIDS 2019; 33:1773–1780.
24. John SA, Parsons JT, Rendina HJ, et al. Club drug users had higher odds of reporting a bacterial STI compared with non-club drug users: Results from a cross-sectional analysis of gay and bisexual men on HIV pre-exposure prophylaxis. Sex Transm Infect 2019; 95:626–628.
25. Hoornenborg E, Coyer L, Achterbergh RCA, et al. Sexual behaviour and incidence of HIV and sexually transmitted infections among men who have sex with men using daily and event-driven pre-exposure prophylaxis in AMPrEP: 2 Year results from a demonstration study. Lancet HIV 2019; 6:e447–e455.
26. Tan DHS, Schnubb A, Lawless J, et al. Acceptability and tolerability of and adherence to HIV preexposure prophylaxis among Toronto gay and bisexual men: A pilot study. CMAJ Open 2018; 6:E611–E617.
27. Nguyen VK, Greenwald ZR, Trottier H, et al. Incidence of sexually transmitted infections before and after preexposure prophylaxis for HIV. AIDS 2018; 32:523–530.
28. Beymer MR, DeVost MA, Weiss RE, et al. Does HIV pre-exposure prophylaxis use lead to a higher incidence of sexually transmitted infections? A case-crossover study of men who have sex with men in Los Angeles, California. Sex Transm Infect 2018; 94:457–462.
29. Mayer KH, Maloney KM, Levine K, et al. Sociodemographic and clinical factors associated with increasing bacterial sexually transmitted infection diagnoses in men who have sex with men accessing care at a boston community health center (2005–2015). Open Forum Infect Dis 2017; 4:ofx214.
30. Marcus JL, Hurley LB, Hare CB, et al. Preexposure prophylaxis for HIV prevention in a large integrated health care system: Adherence, renal safety, and discontinuation. J Acquir Immune Defic Syndr 2016; 73:540–546.
31. Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med 2015; 373:2237–2246.
32. Owens DK, Davidson KW, Krist AH, et al. Preexposure prophylaxis for the prevention of HIV infection: US Preventive Services Task Force Recommendation Statement. JAMA 2019; 321:2203–2213.
33. Thienkrua W, Todd CS, Chonwattana W, et al. Incidence of and temporal relationships between HIV, herpes simplex II virus, and syphilis among men who have sex with men in Bangkok, Thailand: An observational cohort. BMC Infect Dis 2016; 16:340.
34. Wang Y, Huang Y, Chen H, et al. Incidence and correlates of HIV and syphilis in a prospective cohort of men who have sex with men in Mianyang, China, over a 36-month period. Sex Health 2015; 12:546–555.
35. Sentís A, Martin-Sanchez M, Arando M, et al. Sexually transmitted infections in young people and factors associated with HIV coinfection: An observational study in a large city. BMJ Open 2019; 9:e027245.
36. Otieno F, Ng'ety G, Okall D, et al. Incident gonorrhoea and chlamydia among a prospective cohort of men who have sex with men in Kisumu, Kenya. Sex Transm Infect 2020; 96:521–527.
37. van Bilsen WPH, Boyd A, van der Loeff MFS, et al. Diverging trends in incidence of HIV versus other sexually transmitted infections in HIV-negative MSM in Amsterdam. AIDS 2020; 34:301–309.
38. Montaño MA, Dombrowski JC, Dasgupta S, et al. Changes in sexual behavior and STI diagnoses among MSM initiating PrEP in a clinic setting. AIDS Behav 2019; 23:548–555.
39. Werner RN, Gaskins M, Nast A, et al. Incidence of sexually transmitted infections in men who have sex with men and who are at substantial risk of HIV infection—A meta-analysis of data from trials and observational studies of HIV pre-exposure prophylaxis. PLoS One 2018; 13:e0208107.
40. Chan PA, Glynn TR, Oldenburg CE, et al. Implementation of preexposure prophylaxis for human immunodeficiency virus prevention among men who have sex with men at a New England sexually transmitted diseases clinic. Sex Transm Dis 2016; 43:717–723.
41. Cohen SE, Vittinghoff E, Bacon O, et al. High interest in preexposure prophylaxis among men who have sex with men at risk for HIV infection: Baseline data from the US PrEP demonstration project. J Acquir Immune Defic Syndr 2015; 68:439–448.
42. Traeger MW, Schroeder SE, Wright EJ, et al. Effects of pre-exposure prophylaxis for the prevention of human immunodeficiency virus infection on sexual risk behavior in men who have sex with men: A systematic review and meta-analysis. Clin Infect Dis 2018; 67:676–686.
43. Grant JS, Stafylis C, Celum C, et al. Doxycycline prophylaxis for bacterial sexually transmitted infections. Clin Infect Dis 2020; 70:1247–1253.
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