Men who have sex with men (MSM) in the United States are disproportionately affected by human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs). Men who have sex with men accounted for half of prevalent HIV cases in the US by the end of 20081; of the estimated 48,100 incident HIV cases in 2009, most (61%) occurred in gay and bisexual men.2 The median prevalence of Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) among US MSM attending STD Surveillance Network clinics in 2010 (including rectal, urethral, and oropharyngeal infections with these pathogens) was 15.5% and 13.0%, respectively.3 Focusing just on rectal GC and CT, prevalence estimates in MSM as high as 38% for rectal GC4 and 24% for rectal CT5 have been documented. By contrast, in nationally representative National Health and Nutrition Examination Survey data, 14- to 39-year-old men and women had a urethral GC and CT prevalence of 0.24% and 2.2%, respectively.6
Nearly 2 decades of epidemiologic data confirm a dangerous synergy between HIV and other STDs.7,8 It is plausible that rectal STDs increase the risk of HIV transmission and acquisition through anal intercourse. Only one study has evaluated the differences in rectal HIV shedding among MSM with rectal GC/CT compared with MSM without rectal GC/CT 9; those authors reported no differences in HIV shedding among MSM with rectal GC/CT compared with MSM without GC/CT. However, correlations exist between HIV, rectal GC, and rectal CT among MSM using STD Surveillance Network data: rectal GC and CT prevalences in 2010 were 8.1% and 11.7% in HIV-uninfected MSM and 14.4% and 19.6% in HIV-infected MSM.3
Given existing data suggesting that rectal GC and CT may differ by HIV status among MSM, we undertook a project in an urban, public STD clinic in a midwestern US city. Our study had 2 aims: (1) to assess the prevalence of rectal GC and rectal CT among MSM reporting receptive anal intercourse (RAI) in the last 12 months and (2) to examine the associations between HIV status and prevalence of rectal GC/CT in the same population of MSM.
Study Design and Setting
This retrospective, cross-sectional study was conducted in a public STD clinic housed within a city health department. Per clinic protocol, any clinic attendee who reports RAI in the past year undergoes screening for rectal CT and GC testing by culture. The present analysis is an examination of all rectal CT and GC screening performed in male clinic attendees in the 14-month period from November 2010 to December 2011. No exclusion criteria were applied.
From May through December 2011, MSM undergoing screening for rectal GC and CT via culture were also screened using nucleic acid amplification testing (NAAT) as part of an in-house laboratory validation study.
Rectal GC cultures were performed in-house on Thayer-Martin media using standard culture methods. Rectal CT cultures were performed by the Laboratory Corporation of America (LabCorp, Dublin, OH), the clinic reference laboratory, per standard procedures. Nucleic acid amplification testing was performed using Aptima Combo 2 Assay with Tigris (Gen-Probe, San Diego, CA). All indeterminate NAAT results for rectal GC/CT were repeated. If the repeat test was conclusive, those results were reported; if it remained indeterminate, the result was reported as indeterminate. All clinic attendees are also screened for urethral GC and CT via NAAT on urine specimens; syphilis either via rapid plasma reagin (RPR) titers with reactive rapid plasma reagins confirmed by fluorescent treponemal antibody absorption assay or Treponema pallidum passive particle agglutination assay from serum, or dark-field microscopy from any suspected syphilitic chancre; and HIV via OraQuick (OraSure Technologies, Inc, Bethlehem, PA) or Uni-Gold (Trinity Biotech, Bray, Ireland) rapid tests using plasma. Preliminary HIV-positive results are confirmed via Western blot analysis by the Ohio Department of Health.
Data Collection and Extraction
A complete list of men undergoing rectal GC and CT testing during the study period was obtained from clinic billing records. We then extracted relevant behavioral, demographic, and clinical data from electronic medical records. All patients complete a self-administered, 1-page Sexual Health Self-Assessment Form at each visit that captures data about previous STD diagnoses and treatment, HIV status, sexual behavior in the last year, intravenous drug use, and the number and sex of partners. Relevant behavioral variables for this analysis from the Sexual Health Self-Assessment Form were also extracted.
Data analysis was performed using SAS version 9.2 (SAS Institute, Cary, NC). We calculated the prevalence of rectal GC and CT (primary outcomes) separately and as a combined GC/CT outcome. We computed prevalences separately for testing done via culture and during the NAAT validation study. We computed simple frequency statistics of demographic and behavioral data. Finally, we conducted multivariable logistic regression analyses with generalized estimating equations and robust variance estimation10 to account for repeat visits by some patients. After adjustment for relevant confounders, we assessed the association between (a) HIV status and rectal GC via culture, (b) HIV and rectal CT via culture, and (c) HIV and rectal GC/CT via culture (combined outcome). We began with fully adjusted models that were reduced using manual backward-elimination procedures.11 Variables were retained in the final models if their removal from any individual model led to a change in the HIV-rectal GC/CT association of 10% or greater. Statistical significance was defined as P < 0.05.
We conducted 2 sensitivity analyses to evaluate the robustness of our observed measures of effect. First, we restricted the analysis to include only men’s first visits to the clinic within the study window; successive visits by repeat attendees were excluded to determine whether our primary findings were skewed by the presence of men who returned for multiple visits. Second, we repeated all primary analyses using rectal GC and CT results via NAAT, for the subset of participants in the NAAT validation sample.
The study was approved by the Ohio State University institutional review board. All study procedures were undertaken in accordance with the Helsinki Declaration of 1975, as revised in 2000.
A total of 326 men were screened for rectal CT and GC via culture during the study period. Twenty-four men (7%) returned 2 times within the study window, and 4 men (1%) returned 3 times; the analysis data set thus includes 354 study visits. During the NAAT validation study, 125 men from the larger sample were screened for rectal GC and CT using both NAAT and culture methods.
Demographic, Behavioral, and Clinical Characteristics
Participants were predominantly black (37%) or white (57%), with a median age of 27 years. Most men (86%) had at least a high school education. Almost all (92%) were unmarried. Ten percent reported sex with women in the last year, and 88% reported ever having sex without condoms in the last year. One in 10 men reported sex in the last year with a partner known to be HIV positive. More than a quarter (27%) reported sex in the last year with a partner of unknown HIV status, and a similar proportion reported sex with an anonymous partner. A third of men reported sex in the last year while under the influence of drugs or alcohol. Characteristics and reported behaviors of men in the subset undergoing rectal GC/CT screening via NAAT were not meaningfully different from the full sample (Table 1).
STD and HIV Prevalence
By culture methods, the prevalence of rectal GC, CT, and either infection in the full study sample was 9%, 9%, and 15%, respectively. In the sample undergoing screening via NAAT, the prevalence of rectal GC, CT, and either infection was 24%, 23%, and 38%, respectively. Among individuals tested by both culture and NAAT, no one had a positive culture and a negative NAAT result.
In the overall sample, 7% of men had urethral GC, 5% had urethral CT, and 12% had either urethral infection. Twenty-five (78%) of 32 men who had rectal GC via culture were tested negative for urethral GC, and 19 (63%) of 30 men who had rectal GC via NAAT were tested negative for urethral GC. Thirty (97%) of 31 men who had rectal CT via culture were tested negative for urethral CT, and 28 (97%) of 29 men who had rectal CT via NAAT were tested negative for urethral CT.
Almost a quarter (24%) of men in the full cohort had tested positive for HIV before their clinic visit; another 7% tested newly HIV positive on the day of their visit. Thus, total HIV prevalence was 31%. Syphilis prevalence was 17%. Of syphilis-positive men, 5% had primary syphilis, 53% had secondary syphilis, 13% had early latent syphilis, 13% had late latent syphilis, and 15% had latent syphilis of unknown duration.
Rectal STD prevalence differed by HIV status (Fig. 1A, B). With one exception (rectal GC detected by culture), the prevalence of rectal infections was lower among HIV-negative men than among HIV-positive men. We observed no significant differences in rectal GC or CT between men newly diagnosed as having HIV and those diagnosed as having HIV before the current visit. Similar patterns were seen in the subset undergoing NAAT, with wider confidence intervals (CIs) given the smaller sample size.
Symptoms of Rectal Infection
Most patients undergoing testing (85%) reported no symptoms (Table 2). Sixty-nine percent of MSM who tested positive for rectal GC (via culture) and 58% of men who tested positive for rectal CT (via culture) reported no symptoms. Similarly, in 88% of men overall the clinician observed no signs of infection, including 58% of men with rectal CT and 78% of men with rectal GC. The most common clinician-observed sign of infection was proctitis, seen in 23% of men with rectal CT and 13% of men with rectal GC (Table 2).
Unadjusted and Adjusted Associations Between HIV and Rectal GC/CT Via Culture
We assessed age, race, sex without a condom in the last year; syphilis status at the present visit, and the number of sex partners in the last year as potential confounders of the associations between HIV and rectal GC, rectal CT, and rectal GC/CT. According to our a priori criteria for confounding, all final multivariable models were adjusted for age, race, and any sex without a condom in the last year.
HIV status (positive vs. negative, without stratification by timing of HIV diagnosis) was not associated with rectal GC prevalence in unadjusted or adjusted analyses (Table 3). However, HIV-positive status was associated with increased prevalence of rectal CT in unadjusted analyses (odds ratio [OR], 2.18; 95% CI, 1.04–4.60); after adjustment, this significant association was strengthened (OR, 3.14; 95% CI, 1.37–7.19) (Table 3).
Sensitivity Analysis 1: Restriction of the Analysis Sample to First Visits Only
When the analysis was restricted to men’s first visits only (n = 326), the unadjusted and adjusted associations between HIV and rectal STDs were remarkably similar to the primary findings. For example, the adjusted OR for the association between HIV and rectal CT was 3.12 (95% CI, 1.33–7.33) in this sensitivity analysis compared with an OR of 3.14 (95% CI, 1.37–7.19) in the primary findings. All other associations in the restricted sample were also similar to the primary findings; no measure changed from statistically significant to nonsignificant or vice versa (data not shown).
Sensitivity Analysis 2: Unadjusted and Adjusted Associations Between HIV and Rectal GC/CT Via NAAT
We also assessed the associations between HIV status and rectal GC, rectal CT, and rectal GC/CT in the subset of men undergoing NAAT (Table 4). The results were very similar to those obtained using rectal GC and CT status via culture. HIV status was not significantly associated with rectal GC in unadjusted or adjusted analyses. HIV-positive status was significantly associated with increased rectal CT prevalence in unadjusted (OR, 2.58; 95% CI, 1.09–6.09) and adjusted analyses (OR, 3.02; 95% CI, 1.18–7.71) (Table 4).
In this cross-sectional study of MSM reporting RAI in the last year, the prevalence of both rectal GC and rectal CT was generally higher than the prevalence of these rectal infections in other MSM populations in the United States.9,12–18 In our sample, nearly 1 in 7 MSM in whom rectal STD screening was recommended tested positive for rectal GC or CT via culture, and more than 1 in 3 had rectal GC or CT via NAAT. A sizable proportion of our study population were HIV positive, including several individuals newly diagnosed as having HIV on the date of the clinic visit. We observed a significantly increased prevalence of rectal CT among HIV-positive MSM, but the prevalence of rectal GC was not significantly different by HIV status.
Nearly 2 decades of epidemiologic research worldwide confirms synergy between STDs and HIV across a range of populations. Both ulcerative (e.g., herpes simplex virus type 2 and syphilis) and inflammatory STDs (e.g., GC and CT) potentiate HIV acquisition and transmission.8 Among HIV-negative individuals, the odds of HIV acquisition are increased in the presence of CT, GC, trichomoniasis, and genital ulcers.19–21 In HIV-infected individuals, detection of HIV in genital secretions is significantly increased in the presence of urethritis, cervicitis, GC, CT, vulvovaginal candidiasis, and genital ulcer disease.22 Appropriate treatment of STDs or STD-associated inflammation (e.g., cervicitis and urethritis) significantly reduces HIV shedding in vaginal/cervical and seminal secretions.23,24
Despite the documented high rates of both HIV and other STDs among MSM, and existing evidence of HIV-STD synergy in non-MSM populations, HIV-STD synergy for rectal STDs and HIV has not been well studied. One retrospective cohort study in San Francisco reported that MSM with 2 prior rectal GC or CT infections had an 8-fold increased risk of HIV acquisition.25 Another study of HIV-positive MSM reported no difference in rectal HIV shedding among MSM with rectal GC/CT compared with MSM without rectal GC or CT9; however, that study was underpowered to evaluate the confounding effects of antiretroviral therapy or other STDs.9 A large, well-designed, prospective study of the associations between rectal GC and CT, rectal inflammation, and rectal HIV shedding is essential to understand the role of each of these factors in HIV transmission dynamics in MSM.
As expected, most men in our sample reported no symptoms. However, among men with diagnosed infections, symptoms were reported more frequently among men with rectal CT than among men with rectal GC. This counterintuitive finding raises the possibility that some CT-positive men may have been infected with a lymphogranuloma venereum serovar, which can present with proctitis and proctocolitis.26 Unfortunately, we did not perform CT serological testing or polymerase chain reaction–based lymphogranuloma venereum genotyping on patients with positive CT cultures, and our validated NAAT does not distinguish between CT serovars.
We, like others,15 found that screening MSM who report RAI for GC and CT only using urine/urethral specimens would lead to a large proportion of positive rectal infections not being treated. Depending on which infection and which diagnostic approach, between 63% and 97% of rectal GC or CT infections in our study population would not have been diagnosed—because those individuals did not also have a concurrent urethral infection with the same pathogen—if only urine screening for GC and CT had been implemented. Current Centers for Disease Control and Prevention (CDC) guidelines recommend that all MSM who report RAI within the past year undergo annual screening for rectal GC and CT and, more frequently, if high-risk behavioral factors are present.27 Rectal specimens are not approved by the US Food and Drug Administration for GC/CT detection via NAAT, but CDC considers NAAT the optimal modality for rectal GC and CT diagnosis.27 Many large reference laboratories have performed NAAT validation studies for oral and rectal GC/CT detection, and CDC offers guidance to laboratories that seek to perform their own validation studies. However, considerable data suggest that guidelines for the type and frequency of rectal STD testing are not routinely followed, even among HIV-infected men.28,29 Our findings provide further confirmation that screening and treatment of these rectal infections are very much needed.
This retrospective, cross-sectional study has important limitations. First, given the simultaneous measurement of HIV and rectal STD, the temporality of the observed association between HIV and rectal CT cannot be definitively established. Second, several of the sexual behavior variables we assessed are self-reported and may suffer from recall and social desirability biases often present with measurement of sensitive behaviors. Third, the behavioral data used in these analyses were extracted from the self-administered Sexual Health Self-Assessment Form. Patients with limited literacy may not have correctly completed that form. We have no way to assess whether patients fully comprehended the questions on that form. Fourth, some selection bias may be present in our assessed sample. For example, we do not know if all clinicians followed CDC’s screening guidelines for rectal STD for all patients reporting RAI in the past year with the same fidelity. Some clinicians may have only ordered rectal STD screening for patients they perceived to be at particularly increased risk for rectal infection, despite clear recommendations that all patients reporting RAI in the last year should undergo screening. Our analysis also has important strengths. We assessed the association between HIV and rectal GC and CT using both the standard diagnostic method (culture) and the newer, recommended NAAT method. We performed sensitivity analysis to assess the robustness of the observed associations, and although (as expected) the prevalence of rectal infections was higher using NAAT than culture methods for diagnosis, the magnitude of the associations with HIV was similar.
In summary, rectal GC and CT are highly prevalent among MSM reporting RAI in the last year and presenting for screening at an STD clinic in a midwestern US city. Rectal GC and CT are curable, and available diagnostic methodologies (especially NAAT) are sensitive and specific for their accurate detection. Because NAAT is standard for urethral and cervical GC/CT screening, the required equipment and personnel to implement more widespread screening for rectal GC/CT already exist. However, the lack of Food and Drug Administration approval of GC/CT screening via NAAT for extragenital sites is likely a barrier to more widespread availability of this superior screening modality. Assisting STD clinics in provision of rectal NAAT screening is thus an important public health priority. Men who have sex with men in the United States have critical unmet sexual health needs, reflected in their disproportionate and exceedingly high HIV and STD rates. Future interventions focused on better rectal STD screening and treatment in MSM may significantly impact HIV transmission dynamics in this most affected group.
1. CDC. HIV surveillance—United States, 1981–2008. MMWR Morb Mortal Wkly Rep 2011; 60: 689–693.
2. Prejean J, Song R, Hernandez A, et al. Estimated HIV incidence in the United States, 2006–2009. PLoS One 2011; 6: e17502.
3. CDC. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2010. Atlanta: U.S. Department of Health and Human Services, 2011.
4. Manavi K, Zafar F, Shahid H. Oropharyngeal gonorrhoea: rate of co-infection with sexually transmitted infection, antibiotic susceptibility and treatment outcome. Int J STD AIDS 2010; 21: 138–140.
5. McMillan A, Manavi K, Young H. Concurrent gonococcal and chlamydial infections among men attending a sexually transmitted diseases clinic. Int J STD AIDS 2005; 16: 357–361.
6. Datta SD, Sternberg M, Johnson RE, et al. Gonorrhea and chlamydia in the United States among persons 14 to 39 years of age, 1999 to 2002. Ann Intern Med 2007; 147: 89–96.
7. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: The contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect. 1999; 75: 3–17. [Review]
8. Wasserheit JN. Epidemiological synergy. Interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases. Sex Transm Dis. 1992; 19: 61–77. [Review]
9. Kelley CF, Haaland RE, Patel P, et al. HIV-1 RNA rectal shedding is reduced in men with low plasma HIV-1 RNA viral loads and is not enhanced by sexually transmitted bacterial infections of the rectum. J Infect Dis 2011; 204: 761–767.
10. Zeger SL, Liang KY, Albert PS. Models for longitudinal data: A generalized estimating equation approach. Biometrics 1988; 44: 1049–1060.
11. Selvin S. Statistical Analysis of Epidemological Data. 3rd ed. New York: Oxford University Press, 2004.
12. Bachmann LH, Johnson RE, Cheng H, et al. Nucleic acid amplification tests for diagnosis of Neisseria gonorrhoeae
and Chlamydia trachomatis
rectal infections. J Clin Microbiol 2010; 48: 1827–1832.
13. Baker J, Plankey M, Josayma Y, et al. The prevalence of rectal, urethral, and pharyngeal Neisseria gonorrheae
and Chlamydia trachomatis
among asymptomatic men who have sex with men in a prospective cohort in Washington, D.C. AIDS Patient Care STDS 2009; 23: 585–588.
14. Davis TW, Goldstone SE. Sexually transmitted infections as a cause of proctitis in men who have sex with men. Dis Colon Rectum 2009; 52: 507–512.
15. Kent CK, Chaw JK, Wong W, et al. Prevalence of rectal, urethral, and pharyngeal chlamydia and gonorrhea detected in 2 clinical settings among men who have sex with men: San Francisco, California, 2003. Clin Infect Dis 2005; 41: 67–74.
16. Mayer KH, Bush T, Henry K, et al. Ongoing sexually transmitted disease acquisition and risk-taking behavior among US HIV-infected patients in primary care: Implications for prevention interventions. Sex Transm Dis 2012; 39: 1–7.
17. Mimiaga MJ, Helms DJ, Reisner SL, et al. Gonococcal, chlamydia, and syphilis infection positivity among MSM attending a large primary care clinic, Boston, 2003 to 2004. Sex Transm Dis 2009; 36: 507–511.
18. Moncada J, Schachter J, Liska S, et al. Evaluation of self-collected glans and rectal swabs from men who have sex with men for detection of Chlamydia trachomatis
and Neisseria gonorrhoeae
by use of nucleic acid amplification tests. J Clin Microbiol 2009; 47: 1657–1662.
19. Laga M, Manoka A, Kivuvu M, et al. Non-ulcerative sexually-transmitted diseases as risk-factors for HIV-1 transmission in women—Results from a cohort study. AIDS 1993; 7: 95–102.
20. Plummer FA, Simonsen JN, Cameron DW, et al. Cofactors in male-female sexual transmission of human immunodeficiency virus type 1. J Infect Dis 1991; 163: 233–239.
21. Rottingen JA, Cameron DW, Garnett GP. A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV: How much really is known? Sex Transm Dis. 2001; 28: 579–597. [Review]
22. Johnson LF, Lewis DA. The effect of genital tract infections on HIV-1 shedding in the genital tract: A systematic review and meta-analysis. Sex Transm Dis 2008; 35: 946–959.
23. Cohen MS, Hoffman IF, Royce RA, et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: Implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group. Lancet 1997; 349: 1868–1873.
24. McClelland RS, Wang CC, Mandaliya K, et al. Treatment of cervicitis is associated with decreased cervical shedding of HIV-1. AIDS 2001; 15: 105–110.
25. Bernstein KT, Marcus JL, Nieri G, et al. Rectal gonorrhea and chlamydia reinfection is associated with increased risk of HIV seroconversion. J Acquir Immune Defic Syndr 2010; 53: 537–543.
26. Richardson D, Goldmeier D. Lymphogranuloma venereum: An emerging cause of proctitis in men who have sex with men. Int J STD AIDS 2007; 18: 11–14; quiz 5.
27. CDC. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Morb Mortal Wkly Rep 2010; 59: 1–110;
28. Berry SA, Ghanem KG, Page KR, et al. Gonorrhoea and chlamydia testing rates of HIV-infected men: Low despite guidelines. Sex Transm Infect 2010; 86: 481–484.
29. Hoover KW, Butler M, Workowski K, et al. STD screening of HIV-infected MSM in HIV clinics. Sex Transm Dis 2010; 37: 771–776.