Christine M. Khosropour

Standard Treatment Regimens for Nongonococcal Urethritis Have Similar but Declining Cure Rates: A Randomized Controlled Trial

BACKGROUND Azithromycin or doxycycline is recommended for nongonococcal urethritis (NGU); recent evidence suggests their efficacy has declined. We compared azithromycin and doxycycline in men with NGU, hypothesizing that azithromycin was more effective than doxycycline. METHODS From January 2007 to July 2011, English-speaking males ≥16 years, attending a sexually transmitted diseases clinic in Seattle, Washington, with NGU (visible urethral discharge or ≥5 polymorphonuclear leukocytes per high-power field [PMNs/HPF]) were eligible for this double-blind, parallel-group superiority trial. Participants received active azithromycin (1 g) + placebo doxycycline or active doxycycline (100 mg twice daily for 7 days) + placebo azithromycin. Urine was tested for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Ureaplasma urealyticum biovar 2 (UU-2), and Trichomonas vaginalis (TV) using nucleic acid amplification tests. Clinical cure (<5 PMNs/HPF with or without urethral symptoms and absence of discharge) and microbiologic cure (negative tests for CT, MG, and/or UU-2) were determined after 3 weeks. RESULTS Of 606 men, 304 were randomized to azithromycin and 302 to doxycycline; CT, MG, TV, and UU-2 were detected in 24%, 13%, 2%, and 23%, respectively. In modified intent-to-treat analyses, 172 of 216 (80%; 95% confidence interval [CI], 74%-85%) receiving azithromycin and 157 of 206 (76%; 95% CI, 70%-82%) receiving doxycycline experienced clinical cure (P = .40). In pathogen-specific analyses, clinical cure did not differ by arm, nor did microbiologic cure differ for CT (86% vs 90%, P = .56), MG (40% vs 30%, P = .41), or UU-2 (75% vs 70%, P = .50). No unexpected adverse events occurred. CONCLUSIONS Clinical and microbiologic cure rates for NGU were somewhat low and there was no significant difference between azithromycin and doxycycline. Mycoplasma genitalium treatment failure was extremely common. Clinical Trials Registration.NCT00358462.

Bias in Online Recruitment and Retention of Racial and Ethnic Minority Men Who Have Sex With Men

Background The Internet has become an increasingly popular venue for men who have sex with men (MSM) to meet potential sex partners. Given this rapid increase in online sex-seeking among MSM, Internet-based interventions represent an important HIV (human immunodeficiency virus) prevention strategy. Unfortunately, black and Hispanic MSM, who are disproportionately impacted by the HIV epidemic in the United States, have been underrepresented in online research studies. Objective Our objective was to examine and quantify factors associated with underrecruitment and underretention of MSM of color in an online HIV behavioral risk research study of MSM recruited from an online social networking site. Methods Internet-using MSM were recruited through banner advertisements on MySpace.com targeted at men who reported in their MySpace profile their age as at least 18 and their sexual orientation as gay, bisexual, or unsure. Multivariable logistic regression models were used to estimate the odds stratified by race and ethnicity of the MySpace user clicking through the banner advertisement. To characterize survey retention, Kaplan-Meier survival curves and multivariable Cox proportional hazards models identified factors associated with survey dropout. Results Over 30,000 MySpace users clicked on the study banner advertisements (click-through rate of 0.37%, or 30,599 clicks from 8,257,271 impressions). Black (0.36% or 6474 clicks from 1,785,088 impressions) and Hispanic (0.35% or 8873 clicks from 2,510,434 impressions) MySpace users had a lower click-through rate compared with white (0.48% or 6995 clicks from 1,464,262 impressions) MySpace users. However, black men had increased odds of click-through for advertisements displaying a black model versus a white model (adjusted odds ratio [OR] = 1.83, 95% confidence interval [CI] 1.72 - 1.95), and Hispanic participants had increased odds of click-through when shown an advertisement displaying an Asian model versus a white model (adjusted OR = 1.70, 95% CI 1.62 - 1.79). Of the 9005 men who consented to participate, 6258 (69%) completed the entire survey. Among participants reporting only male sex partners, black non-Hispanic and Hispanic participants were significantly more likely to drop out of the survey relative to white non-Hispanic participants (hazard ratio [HR] = 1.6, 95% CI 1.4 - 1.8 and HR = 1.3, 95% CI 1.1 - 1.4, respectively). Men with a college-level of education were more likely to complete the survey than those with a high-school level of education (HR = 0.8, 95% CI 0.7 - 0.9), while men who self-identified as heterosexual were more likely to drop out of the survey compared with men who self-identified as gay (HR = 2.1, 95% CI 1.1 - 3.7). Conclusions This analysis identified several factors associated with recruitment and retention of MSM in an online survey. Differential click-through rates and increased survey dropout by MSM of color indicate that methods to recruit and retain black and Hispanic MSM in Internet-based research studies are paramount. Although targeting banner advertisements to MSM of color by changing the racial/ethnic composition of the advertisements may increase click-through, decreasing attrition of these study participants once they are engaged in the survey remains a challenge.

Willingness of US men who have sex with men (MSM) to participate in Couples HIV Voluntary Counseling and Testing (CVCT).

Background We evaluated willingness to participate in CVCT and associated factors among MSM in the United States. Methods 5,980 MSM in the US, recruited through MySpace.com, completed an online survey March-April, 2009. A multivariable logistic regression model was built using being “willing” or “unwilling” to participate in CVCT in the next 12 months as the outcome. Results Overall, 81.5% of respondents expressed willingness to participate in CVCT in the next year. Factors positively associated with willingness were: being of non-Hispanic Black (adjusted odds ratio [aOR]: 1.5, 95% confidence interval [CI]: 1.2–1.8), Hispanic (aOR: 1.3, CI: 1.1–1.6), or other (aOR: 1.4, CI: 1.1–1.8) race/ethnicity compared to non-Hispanic White; being aged 18–24 (aOR: 2.5, CI: 1.7–3.8), 25–29 (aOR: 2.3, CI: 1.5–3.6), 30–34 (aOR: 1.9, CI: 1.2–3.1), and 35–45 (aOR: 2.3, CI: 1.4–3.7) years, all compared to those over 45 years of age; and having had a main male sex partner in the last 12 months (aOR: 1.9, CI: 1.6–2.2). Factors negatively associated with willingness were: not knowing most recent male sex partner’s HIV status (aOR: 0.81, CI: 0.69–0.95) compared to knowing that the partner was HIV-negative; having had 4–7 (aOR: 0.75, CI: 0.61–0.92) or >7 male sex partners in the last 12 months (aOR: 0.62, CI: 0.50–0.78) compared to 1 partner; and never testing for HIV (aOR: 0.38, CI: 0.31–0.46), having been tested over 12 months ago (aOR: 0.63, CI: 0.50–0.79), or not knowing when last HIV tested (aOR: 0.67, CI: 0.51–0.89), all compared to having tested 0–6 months previously. Conclusions Young MSM, men of color, and those with main sex partners expressed a high level of willingness to participate in couples HIV counseling and testing with a male partner in the next year. Given this willingness, it is likely feasible to scale up and evaluate CVCT interventions for US MSM.

Willingness to Take a Free Home HIV Test and Associated Factors among Internet-Using Men Who Have Sex with Men.

Objectives: Online HIV prevention studies have been limited in their ability to obtain biological specimens to measure study outcomes. We describe factors associated with willingness of men who have sex with men (MSM) to take a free home HIV test as part of an online HIV prevention study. Methods: Between March and April 2009, we interviewed 6163 HIV-negative MSM and assessed the willingness to test for HIV infection using a home collection kit. Results: Men reported being very likely (3833; 62%) or likely (1236; 20%) to accept a home HIV test as part of an online HIV prevention study. The odds of being willing to home test were higher for men who were offered incentives of

Comparing azithromycin and doxycycline for the treatment of rectal chlamydial infection: a retrospective cohort study.

10 or

High prevalence of sexual concurrency and concurrent unprotected anal intercourse across racial/ethnic groups among a national, Web-based study of men who have sex with men in the United States.

25, were black, had unprotected anal intercourse in the past 12 months, and were unaware of their HIV status. Conclusions: Home testing offered as part of online HIV prevention research is acceptable overall and in important subgroups of high-risk MSM.

Bacterial vaginosis-associated bacteria in men: association of Leptotrichia/Sneathia spp. with nongonococcal urethritis.

Background Centers for Disease Control and Prevention guidelines recommend azithromycin or doxycycline for treatment of rectal chlamydial infection. Methods We created a retrospective cohort of male patients diagnosed as having rectal chlamydia between 1993 and 2012 at a sexually transmitted disease clinic in Seattle, Washington. Men were included in the analysis if they were treated with azithromycin (1 g single dose) or doxycycline (100 mg twice a day × 7 days) within 60 days of chlamydia diagnosis and returned for repeat testing 14 to 180 days after treatment. We compared the risk of persistent/recurrent rectal chlamydial infection among recipients of the 2 drug regimens using 4 follow-up testing time intervals (14–30, 60, 90, and 180 days). Results Of 1835 cases of rectal chlamydia diagnosed in the study period, 1480 (81%) were treated with azithromycin or doxycycline without a second drug active against Chlamydia trachomatis. Of these, 407 (33%) of 1231 azithromycin-treated men and 95 (38%) of 249 doxycycline-treated men were retested 14 to 180 days after treatment (P = 0.12); 88 (22%) and 8 (8%), respectively, had persistent/recurrent infection (P = 0.002). Persistent/recurrent infection was higher among men treated with azithromycin compared with doxycycline at 14 to 30 days (4/53 [8%] vs. 0/20 [0%]), 14 to 60 days (23/136 [17%] vs. 0/36 [0%]), and 14 to 90 days (50/230 [22%] vs. 2/56 [4%]). In multivariate analysis, azithromycin-treated men had a significantly higher risk of persistent/recurrent infection in the 14 to 90 days (adjusted relative risk, 5.2; 95% confidence interval, 1.3–21.0) and 14 to 180 days (adjusted relative risk, 2.4; 95% confidence interval, 1.2–4.8) after treatment. Conclusions These data suggest that doxycycline may be more effective than azithromycin in the treatment of rectal chlamydial infections.

Enhancing Retention of an Internet-Based Cohort Study of Men Who Have Sex With Men (MSM) via Text Messaging: Randomized Controlled Trial

Background Men who have sex with men (MSM) are the largest human immunodeficiency virus (HIV) risk group in the United States. Sexual concurrency may contribute to high HIV incidence or to racial/ethnic HIV disparities among MSM. Limited information is available on concurrency and racial/ethnic differences among MSM or on the extent to which MSM engage in concurrent unprotected anal intercourse (UAI). Methods Data are from baseline responses in a prospective online study of MSM aged 18 years or older, having 1 or more male sex partners in the past 12 months, and recruited from social networking Web sites. Pairwise sexual concurrency and UAI in the previous 6 months among up to 5 recent partners was measured, using an interactive questionnaire. Period prevalences of concurrency and concurrent UAI were computed and compared across racial/ethnic groups at the individual and triad (a respondent and 2 sex partners) levels. Results A total of 2940 MSM reported on 8911 partnerships; 45% indicated concurrent partnerships, and 16% indicated concurrent UAI in the previous 6 months. Respondents were more likely to have UAI with 2 partners when they were concurrent, compared to serially monogamous (odds ratio, 1.93, 95% confidence interval, 1.75–2.14). No significant differences in levels of individual concurrency or concurrency among triads were found between non-Hispanic white, non-Hispanic black, and Hispanic men. Conclusions Concurrency and concurrent UAI in the previous 6 months was common. Although there were no differences by race/ethnicity, the high levels of concurrency and concurrent UAI may be catalyzing the transmission of HIV among MSM in general.

Predictors of Retention in an Online Follow-up Study of Men Who Have Sex With Men

Background Approximately 45% of nongonococcal urethritis cases have no identified etiology. Novel bacteria recently associated with bacterial vaginosis (BV) in women may be involved. We evaluated the association of idiopathic nongonococcal urethritis and 5 newly described BV-associated bacteria (BVAB). Methods Heterosexual men 16 years or older attending a sexually transmitted disease clinic in Seattle, Washington, from May 2007 to July 2011 and negative for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, and Ureaplasma urealyticum–biovar2 were eligible. Cases had urethral discharge or 5 or more polymorphonuclear leukocytes per high-power field in urethral exudates. Controls had no urethral discharge and less than 5 polymorphonuclear leukocytes per high-power field. Urine was tested for Atopobium spp., BVAB-2, BVAB-3, Megasphaera spp., and Leptotrichia/Sneathia spp. using quantitative taxon-directed polymerase chain reaction. Results Cases (n = 157) and controls (n = 102) were of similar age, education, and income, and most were white. Leptotrichia/Sneathia spp. was significantly associated with urethritis (24/157 [15.3%] vs. 6/102 [5.9%], P = 0.03). BVAB-2 was more common in cases than in controls (7/157 [4.5%] vs. 1/102 [1.0%], P = 0.15), and BVAB-3 (n = 2) and Megasphaera spp. (n = 1) were only detected in men with urethritis, but these bacteria were found only in men who also had Leptotrichia/Sneathia spp. Atopobium spp. was not associated with urethritis. The quantity of bacteria did not differ between cases and controls. Among treated cases, doxycycline was more effective than azithromycin for clinical cure of men with Leptotrichia/Sneathia spp. (9/10 vs. 7/12, P = 0.16) and BVAB-2 (3/3 vs. 0/3, P = 0.10). Conclusions Leptotrichia/Sneathia spp. may be urethral pathogens or contribute to a pathogenic microbiota that can also include BVAB-2, BVAB-3, and Megasphaera spp. Doxycycline may be more effective than azithromycin against these newly identified bacteria.

Discussion of HIV Status by Serostatus and Partnership Sexual Risk among Internet-Using MSM in the United States

Background Black and Hispanic men who have sex with men (MSM) are disproportionately affected by HIV in the United States. The Internet is a promising vehicle for delivery of HIV prevention interventions to these men, but retention of MSM of color in longitudinal Internet-based studies has been problematic. Text message follow-up may enhance retention in these studies. Objective To compare retention in a 12-month prospective Internet-based study of HIV-negative MSM randomized to receive bimonthly follow-up surveys either through an Internet browser online or through text messages. Methods Internet-using MSM were recruited through banner advertisements on social networking and Internet-dating sites. White, black, and Hispanic men who were ≥18, completed an online baseline survey, and returned an at-home HIV test kit, which tested HIV negative, were eligible. Men were randomized to receive follow-up surveys every 2 months on the Internet or by text message for 12 months (unblinded). We used time-to-event methods to compare the rate of loss-to-follow-up (defined as non-response to a follow-up survey after multiple systematically-delivered contact attempts) in the 2 follow-up groups, overall and by race/ethnicity. Results are reported as hazard ratios (HR) and 95% confidence intervals (CI) of the rate of loss-to-follow-up for men randomized to text message follow-up compared to online follow-up. Results Of 1489 eligible and consenting men who started the online baseline survey, 895 (60%) completed the survey and were sent an at-home HIV test kit. Of these, 710 of the 895 (79%) returned the at-home HIV test kit, tested HIV-negative, and were followed prospectively. The study cohort comprised 66% white men (470/710), 15% (106/710) black men, and 19% (134/710) Hispanic men. At 12 months, 77% (282/366) of men randomized to online follow-up were retained in the study, compared to 70% (241/344) men randomized to text message follow-up (HR=1.30, 95% CI 0.97-1.73). The rate of loss-to-follow-up was non-significantly higher in the text message arm compared to the online arm for both white (HR=1.43, 95% CI 0.97-1.73) and Hispanic men (HR=1.71, 95% CI 0.91-3.23); however, loss-to-follow-up among black men was non-significantly lower among those who received text message follow-up compared to online follow-up (HR=0.78, 95% CI 0.41-1.50). In the online arm, black men were significantly more likely to be lost to follow-up compared to white men (HR=2.25, 95% CI 1.36-3.71), but this was not the case in the text message arm (HR=1.23, 95% CI 0.70-2.16). Conclusions We retained >70% of MSM enrolled in an online study for 12 months; thus, engaging men in online studies for a sufficient time to assess sustained outcomes is possible. Text message follow-up of an online cohort of MSM is feasible, and may result in higher retention among black MSM.