Herpes simplex virus type 2 (HSV-2) is one of the most prevalent causes of genital ulcers.1 A strong synergetic interaction between HSV-2 and human immunodeficiency virus (HIV) has been observed in both in vivo and in vitro studies2,3 and has also been supported by epidemiologic evidence.4–6 Considering the importance of HSV-2 prevention in controlling HIV transmission, some developed countries have integrated HSV-2 serological testing into their national surveillance systems to monitor sexual behavior in their general populations. For example, the National Health and Nutrition Examination Surveys have been continuously conducted in the United States to track the seroprevalence of HSV-2 and HIV infections in the population, with data released every 2 years.7
Men who have sex with men (MSM) have been one of the highest priority populations contributing to the HIV epidemic in China. In recent years, there has been an increasing number of studies on the prevalence of HIV and syphilis infections among the MSM population in China.8,9 However, information on the prevalence and risk factors of HSV-2 and its coinfection with HIV among the MSM population in China is limited.10,11 This study aimed to investigate the prevalence of HSV-2 infection and its coinfection with HIV in MSM to provide baseline data for developing the intervention program.
MATERIALS AND METHODS
Study Population and Survey Approaches
Men were eligible for enrollment in the study if they were more than 18 years of age and reported anal or oral sexual activity with men during the past year. From July 2009 to May 2010, MSM participants were recruited from different settings, including an STD clinic in Shenzhen, a health center in Guangzhou, and several MSM venues in Changzhou. After informed consent was obtained, the men were asked to provide blood samples and were interviewed by outreach workers, using a structured questionnaire consisting of questions related to demographic and behavioral characteristics. The study protocol was reviewed and approved by the Medical Ethics Committee at Institute of Dermatology, the Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China.
Testing for HSV-2 and HIV Infections
Serum specimens were collected and stored at −70°C before the laboratory testing. Enzyme-linked immunosorbent assay (ELISA) (Captia HSV 2 type-specific IgG; Trinity Biotech, Jamestown, NY) was used to test for IgG antibodies to HSV-2 to determine the HSV-2 seropositivity. Antibodies to HIV were screened by ELISA (Anti-HIV1/2 EIA Kit; Livzon Group Reagent Factory, Zhuhai, Guangdong, China) followed by Western blotting (Singapore MP Biomedical Asia Pacific Ltd, Singapore) for confirmation of those positive with the screening test. The specimens that were positive for both HIV ELISA and Western blot tests were considered seropositive for HIV infection.
Descriptive analyses were performed to describe the demographic and behavioral characteristics of all participants. The χ2 test was used to compare the categorized data. The univariate analysis was performed to determine the preliminary association of HSV-2 infection (or HSV-2/HIV coinfection) with demographic and behavioral factors. The variables that were significantly related to the infections at the level of P < 0.05 in the univariate analysis were included into the multivariate logistic regression model. SPSS for Windows (version 13.0, Chicago, IL) was used for the statistical analysis.
Demographic and Behavioral Characteristics of MSM
Of the1462 eligible MSM who participated in the survey, 648 MSM were recruited from the STD clinic, 393 from the health center, and 421 from the MSM venues, such as bars and bathhouses. The mean and the median ages were 30.14 years (standard deviation, 8.6; range, 18–66 years) and 29 years (interquartile range, 23–35 years), respectively. The age of more than half of the participants (n = 872, 59.6%; 95% confidence interval [CI], 57.1%–62.1%) was less than 30 years, and 554 (37.9%; 95% CI, 35.4%–40.4%) participants had an education level higher than senior high school. More than two-thirds of participants (n = 1067, 73.0%; 95% CI, 70.7%–75.2%) were unmarried, and 682 (46.6%; 95% CI, 44.1%–49.2%) reported living alone.
The majority of MSM (n = 1322, 90.4%; 95% CI, 88.8%–91.8%) identified themselves as homosexual men, and 1127 (77.0%; 95% CI, 74.9%–79.2%) had sex only with or mostly with men. Overall, 250 (17.1%; 95% CI, 15.3%–19.1%) MSM reported having involvement with commercial sex work. Of them 175 (70%; 95% CI, 64.0%–75.4%) acted as a sex seller, 200 (80%; 95% CI, 74.6%–84.5%) reported condom use in their last sexual act, and 66 (4.5%; 95% CI, 3.6%–5.7%) reported past history of sexual abuse. Of the 1462 participating MSM, 1232 (84.3%; 95% CI, 82.3%–86.1%) men reported having had anal sex in the past 6 months, among which 376 (30.5%; 95% CI, 23.6%–28.0%) reported having unprotected anal intercourse. Additionally, 480 (32.8%; 95% CI, 30.5%–35.3%) MSM reported having sex with a woman in the past 6 months, of which 237 men (49.5%; 95% CI, 45.0%–53.9%) did not use condoms. The main settings where the study participants found their male sexual partners included internet (46.4%; 95% CI, 43.9%–49.0%), bathhouses (21.6%; 95% CI, 19.6%–23.8%), and bars (14.0%; 95% CI, 12.3%–15.9%).
Prevalence of HSV-2 Infection and Coinfection of HSV-2 and HIV
Of the 1462 MSM, 234 were HSV-2 seropositive (14 ambiguous specimens were not considered seropositive), giving an overall HSV-2 prevalence of 16.0% (95% CI; 14.2%–18.0%). Differences in HSV-2 prevalence were observed in MSM recruited from different settings in the 3 cities (χ2 = 10.34, P = 0.006), with the highest prevalence of 19.2% (81/421; 95% CI, 15.8%–23.3%) in MSM venues in Changzhou, followed by the STD clinic in Shenzhen (18.7%; 95% CI, 15.9%–21.8%) and the health center in Guangzhou (8.1%; 95% CI, 5.8%–11.3%). However, the prevalence in Changzhou was not statistically different from that in Shenzhen (χ2 = 0.02, P = 0.88).
Prevalence of HIV infection among 1462 MSM was 9.5% (95% CI, 8.1–11.1), with 47 men coinfected with HSV-2, providing an overall coinfection rate of 3.2% (95% CI, 2.4%–4.3%). However, the rate was also different from site to site, with the highest rate in Changzhou (5.5%; 95% CI, 3.6%–8.1%) followed by Shenzhen (2.8%; 95% CI, 1.7%–4.4%) and Guangzhou (1.5%; 95% CI, 0.6%–3.4%).
Risk Factors in Univariate Analysis
Table 1 demonstrates the results of the univariate analysis. The factors significantly associated with HSV-2 infection were type of the settings, age group, education level, and marriage status. The men who had a history of sexual abuse had a higher risk of HSV-2 infection. Gender of sexual partners was also associated with HSV-2 infection. MSM who had bisexual behaviors, predominantly having sex with men or women, had a significantly higher prevalence of HSV-2 infection. Involvement in commercial sex work was associated with HSV-2 infection.
According to the univariate analysis, risk factors for the coinfection of HSV-2 and HIV were age >30 years (odds ratio [OR] = 1.9; 95% CI, 1.1–3.4), education level lower than junior high school (OR = 5.7; 95% CI, 2.4–13.3), having a few female sexual partners (OR = 2.4; 95% CI, 1.2–5.0), having equal numbers of male and female partners (OR = 2.4; 95% CI, 1.0–5.6), and history of sexual abuse (OR = 4.1; 95% CI, 1.7–9.4). MSM recruited from the health center or the STD clinic had a lower prevalence of HSV-2/HIV coinfection compared with those recruited from the MSM venues, such as bars and bathhouses (OR = 0.3; 95% CI, 0.1–0.7 for those MSM from health center; OR = 0.5; 95% CI, 0.3–0.9 for those from STD clinic). Unmarried status was a protective factor for HSV-2/HIV coinfection (OR = 0.4; 95% CI, 0.2–0.7).
Risk Factors in Multivariate Analysis
Table 2 displays the results of the multiple logistic regression analysis. HSV-2 infection was independently associated with age >30 years (adjusted OR [AOR], 1.9; 95% CI, 1.4–2.7), lower educational level (for education lower than junior high school, AOR = 2.0; 95% CI, 1.3–2.9), involvement in commercial sex work (AOR = 1.6; 95% CI, 1.1–2.3), and HIV-positive status (AOR = 2.7; 95% CI, 1.8–4.1). Being recruited from the health center (AOR = 0.6; 95% CI, 0.4–0.9) was inversely associated with HSV-2 infection. In addition, the association between HSV-2 and HIV infections was affected by sexual orientation because this association became stronger with an increased proportion of female sexual partners (data not shown).
According to the multivariate analysis of all variables significantly associated with the coinfection of HSV-2 and HIV (P < 0.05) in the univariate analysis, education level lower than junior high school (AOR = 4.4; 95% CI, 1.8–11.1), and history of sexual abuse (AOR = 3.4, 95% CI, 1.4–8.3) were independent risk factors for HSV-2/HIV coinfection.
The study found a substantial HSV-2 prevalence (16.0%) among 1462 MSM from 3 cities in China, but the rate varied from area to area. The overall prevalence is similar to the 15.1% found among MSM in Zhejiang, China, in 200812 and 18.4% found in a study in the United States,7 but lower than the prevalence found in South American countries, such as 45.7% in Brazil and 46.3% in Peru.4,13 The study in one of our study areas (Jiangsu) found an HSV-2 prevalence of 7.8% in 2006, which is much lower than the 16.0% detected in the current study. This difference probably suggests an increase in the prevalence from 2006 to 2010. A recent study in Chengdu of Sichuan Province also showed a high prevalence (24.7%) in 2010.
In this study, age >30 years, education level lower than senior high school, and involvement in commercial sex work were identified as risk factors for HSV-2 infection. As HSV-2 seropositivity reveals a lifetime exposure to the infection, the association between the older age and HSV-2 prevalence might be due to the cumulative effect of a long exposure time to HSV-2. Our study shows that MSM with lower education level usually lack knowledge of STD prevention, such as condom use, and are also more likely to be involved in commercial sex work (data not shown). Because commercial sex workers have higher HSV-2 prevalence,14 their commercial sex work with MSM may result in HSV-2 transmission to MSM. In accordance with our results, increased age13 and the history of commercial sex work10 have also been reported to be associated with HSV-2 infection.
In this study, although married status was not found to be associated with HSV-2 infection, it is worth noting that 27.0% (n = 395) of MSM were married and that most of the unmarried MSM had female sexual partners. This finding is similar to the observations from many previous studies.11,15,16 In light of a high prevalence of HIV infection in MSM and high prevalence of MSM who have heterosexual partners, there is a substantial risk of bridging the HIV epidemic from the MSM population to the general population through MSM transmission to their female sex partners.7,17 This finding has an important implication for developing appropriate intervention strategies.
The overall HIV prevalence among 1462 MSM from 3 study areas was 9.5% (95% CI, 8.1–11.1), which was substantially higher than that (0%) among Chinese MSM in one of the study areas (Jiangsu) several years ago.11 Furthermore, 47 men (3.2%; 95% CI, 2.4–4.3) were coinfected with HSV-2 and HIV. Regarding the geographic distribution of HSV-2 infection, the prevalence of HSV-2 and HIV coinfection was significantly higher in Changzhou (5.5%; 95% CI, 3.6%–8.1%) than in Guangzhou (1.5%; 95% CI, 0.6%–3.4%) or Shenzhen (2.8%; 95% CI, 1.7%–4.4%). MSM recruited from the venues such as bars and bathhouses in Changzhou had the highest risk for HSV-2 and HIV infections. MSM attending the health center in Guangzhou had the lowest risk for HSV-2 and HIV infections. HSV-2 and HIV coinfection was not found in Jiangsu in 2006.11 The rapid increase in the coinfection rate implicates the inadequate implementation of interventions in this particular population in the past. Fortunately, during recent years, the national program has committed increased attentions and invested more resources in the prevention and control of HIV and STDs in the MSM population.
The strengths of this study included the large sample size and multiple recruitment cities. In contrast, some limitations also existed in our study. First, sample selection bias might exist given that all 3 recruitment cities are located in coastal regions of China with well-developed economies. Second, the questionnaire did not include a question regarding number of sexual partners, which was demonstrated in other studies to be a risk factor for HSV-2 infection. Despite of these limitations, our study is a large-scale survey providing important information on the prevalence and risk factors of HSV-2 infection and HSV-2/HIV coinfection among MSM in China.
In summary, this study shows that the prevalence of HSV-2 among MSM in China is substantial and that a significant association exists between HSV-2 and HIV infections. In addition, age >30 years, education level lower than senior high school, and involvement in commercial sex work are risk factors for HSV-2 infection, while education level lower than junior high school and history of sexual abuse are independently associated with the coinfection of HSV-2 and HIV. This is important information for developing effective strategies for reducing HSV-2 infection and HSV-2/HIV coinfection in MSM, which in turn is critical for the control of HIV transmission in this high-risk population.
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