Male Circumcision as a Bio-medical HIV Intervention Targeting Male. Heterosexual Sexually Transmitted Disease (STD) Patients in China.

Transcription

1 Male Circumcision as a Bio-medical HIV Intervention Targeting Male Heterosexual Sexually Transmitted Disease (STD) Patients in China - An Acceptability Study and a Single-arm Test-of-concept Trial WANG, Zixin A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Public Health The Chinese University of Hong Kong August 2013

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3 Abstract (English) Male Circumcision as a Bio-medical HIV Intervention Targeting Male Heterosexual Sexually Transmitted Disease (STD) Patients in China - An Acceptability Study and a Single-arm Test-of-concept Trial WANG, Zixin Doctor of Philosophy in Public Health The Chinese University of Hong Kong (August 2013) Introduction The HIV and sexually transmitted diseases (STD) epidemics are severe in China. Male circumcision (MC) is a newly developed yet under-utilized, evidence-based HIV intervention. The World Health Organization (WHO) and joint United Nations Programme on HIV/AIDS (UNAIDS) recommend its usage as a means of HIV prevention among heterosexual males. Despite the significance, there is no published study investigating the implementation of MC among male STD patients who are of high risk of HIV infection and serve as bridge population transmitting HIV from high risk population to low risk population. Objectives In Phase I cross-sectional study, we aimed to investigate the prevalence and associated factors of willingness to take up MC conditional on STD risk reduction and HIV risk reduction among uncircumcised male STD patients in Shenzhen, China. We also investigated the prevalence and associated factors of anticipated risk compensation due to MC. In Phase II, an intervention was developed based on the results of the acceptability study. A test-of-concept trial was conducted to test the I

4 effectiveness and sustainability of the intervention in promoting MC. Method In Phase I, 308 HIV negative, uncircumcised and consented heterosexual male STD patients recruited from three STD clinics in Shenzhen were interviewed anonymously. In Phase II, another sample of 179 such patients participated in an intervention promoting MC. They were followed up by telephone at month 4. Participants who had taken up MC received another telephone follow up at month 6. A qualitative process evaluation among intervention administrators, clinicians and the directors of the STD clinics was also conducted at month 6. Statistical methods such as Chi-square test, Logistic regression and Cox regression were used in this study. Results Respectively 45.1% and 46.1% of the participants were willing to take up MC in the next six months conditional on STD risk reduction and conditional on HIV risk reduction. We found out that factors associated with acceptability included younger age, HIV/STD-related knowledge, overly long foreskin, cognitive factors including those related to Health Belief Model (HBM) and subjective norm (a TPB construct), as well as emotional factors. Our analysis also found out that subjective norm did not add explanatory power to the HBM factors. In addition, results show a potential mediating effect of emotional representation of STD infection between perceived severity of STD infection and acceptability of MC. 26.9% anticipated at least one type of the aforementioned risk compensation due to MC. Intention to reduce condom use with regular female sex partner (RP) was the II

5 most prevalent type of anticipated risk compensation. Two relative risk assessment variables, perceived risk gap and perceived risk reduction, were both found to be significant factors. Negative condom attitude was another significant factor. Our analysis further showed that the level of negative attitudes toward condom use moderated the association between perceived risk gap and anticipated risk compensation. No interaction was found between intention to take up MC and various associated factors. It is satisfactory that of the sampled male STD patients, 19.9% did actually take up MC within the 4-month follow-up period. This may be a conservative response to the health promotion due to the short follow-up period as 40 uncircumcised participants (25.6%) showed an intention to take up MC. Participants in the TOC trial who had discussed the benefits of MC with their female sex partners, perceived higher behavioral control, had behavioral intention or plans made for taking up MC at the baseline were more likely than others to have actually taken up MC during the study period. Process evaluation obtained from the stakeholders has been extremely positive. However, over one third of circumcised participants reported reducing frequency of condom use with RP after taking up MC. The possibility of risk compensation with non-regular female sex partners or female sex workers cannot be ruled out due to potential reporting bias. Conclusion MC is an evidence-based but under-utilized HIV intervention. We conducted a formative research which was followed by a TOC trial showing potential effectiveness and issues to be addressed. We proposed a stage-approach in improving scaling up of the intervention by promoting MC. We believe that our study is a good III

6 starting point integrating biomedical and behavioral HIV intervention in China, which will create a significant impact on prevention of HIV and STD in China. Moreover, as Asian countries share some similar cultural contexts. Our experiences may contribute to improving their HIV prevention programs. We believe that, through the scaling up of MC, this study will contribute to the control of HIV/STD in China. It is also our sincere wish that this study leads to more implementation studies on HIV/STD prevention in China in the future. IV

7 Abstract (Chinese) 應用包皮環切手術作為預防中國男性性病患者 HIV 感染的生物醫學干預手段 -- 一項可接受性研究及一項測試概念的臨床實驗王子昕公共衛生哲學博士香港中文大學二零一三年八月介紹中國的 HIV 和性傳播疾病 (STD) 流行現狀非常嚴峻 男性性病患者不僅是 HIV 感染的高危人群, 還是將 HIV 由高危人群傳播至低危人群的 橋樑人群 包皮環切手術作為世界衛生組織和聯合國艾滋病規劃署推薦的循證 HIV 生物醫學預防手段, 尚未應用于該人群的 HIV 預防 目的在第一階段橫斷面研究中, 我們首先對深圳市未接受過包皮環切手術的男性性病患者中包皮環切手術的可接受程度進行了調查, 并對影響可接受性的因素進行探討 我們還對該人群中風險補償行為意向的發生率及相關因素進行了研究 在第二階段中, 基於可接受性研究的結果, 我們設計了旨在提高包皮環切手術率的健康促進方法, 并通過一項測試概念的臨床實驗對該健康促進方法的效能和可持續性進行了檢驗 方法 本研究的對象為從深圳市三所性病門診中招募的 HIV 陰性 未接受過包皮 環切 簽署了知情同意 異性性取向的男性性病患者 在第一階段中, 我們對 V

8 308 名符合上述條件的男性性病患者進行了不記名的問卷調查 在第二階段中, 我們對另外 179 名符合上述條件的男性性病患者進行了干預, 并于之后的第四個月對他們進行了電話隨訪 在這四個月期間接受了包皮環切手術的被訪者在干預後六個月再次接受了我們的電話隨訪 在干預后的第六個月進行的項目過程評價中, 我們對干預員, 臨床醫生和性病門診的主任進行了定性電話訪談 統計分析方法包括 Chi-square 檢驗,Logistic 回歸分析以及 Cox 回歸分析等 結果當被告知包皮環切手術可以降低性傳播疾病感染風險后,45.1% 的被訪者有意願在未來六個月內接受包皮環切手術 而當被告知該手術可以降低 HIV 感染風險后, 有意願在未來六個月內接受該手術的比例為 46.1% 我們發現與包皮環切手術可接受性顯著相關的因素包括年齡,HIV/ 性病相關知識, 包皮長度, 與健康信念模型及主觀規範相關的感知變量, 以及情感相關變量 我們同時發現, 將主觀規範加入包含健康信念模型有關變量的模型后, 并不能增加該模型對包皮環切手術可接受性的解釋能力 此外, 針對性病感染的情感陳述在感知性病嚴重程度和包皮環切手術可接受性之間的關係中有中介作用 26.9% 的被訪者存在包皮環切手術后進行風險補償行為的意向 意圖在包皮環切術后減少與固定女性性伴安全套使用頻率是最主要的一種風險補償行為意向 兩個有關相對風險評價的變量, 感知風險差距和感知包皮環切降低風險的程度與風險補償行為意向顯著相關 對安全套使用的消極態度是另外一個顯著因素 此外, 我們發現對安全套使用的消極態度對風險差距與風險補償行為意向之間的關係有調節作用 接受包皮環切手術的意向不會對上述變量與風險補償行為意向之間的關係產生調節作用 VI

9 基於可接受性研究的結果, 我們進行的測試概念的臨床實驗結果令人滿意 參與第四個月隨訪的被訪者中,19.9% 已經接受了包皮環切手術, 另有 40 名被訪者 (25.6%) 仍有意願接受包皮環切手術 在基線調查時表示曾經與女性性伴討論過包皮環切手術的好處, 具有更高的知覺行為控制, 有意向或有計劃接受該手術的被訪者, 具有更高的可能在研究期間接受包皮環切 對干預員 臨床醫生和性病門診的主任進行的項目過程評價結果令人鼓舞 但是, 接受了包皮環切的被訪者中有超過三分之一在術後減少了與固定女性性伴的安全套使用頻率, 由於可能存在的報告偏移, 我們不能排除他們與非固定女性性伴以及女性性工作者發生風險補償行為的可能性 結論包皮環切是一項循證的 HIV 干預手段, 在中國應用很少 我們在前期研究的基礎上, 進行了一項測試概念的臨床實驗, 證明了健康促進方法的效能, 同時也發現了其中存在的問題 我們建議採用循序漸進的方式在中國大規模推進促進包皮環切的干預 我們相信, 本研究是在中國整合生物醫學和行為學 HIV 干預的起點, 將對中國的 HIV 和性病流行現狀產生顯著的影響 由於亞洲國家在風俗文化上存在許多的共同點, 我們的經驗將對提高他們的 HIV 預防工作提供幫助 我們相信, 通過大規模推進包皮環切, 將為中國的 HIV 和性病預防控制工作作出貢獻 我們衷心的希望在中國湧現出更多預防 HIV 和性病的應用型研究 VII

10 Acknowledgement Pursuing my PhD degree in CUHK is a journey full of surprises, excitement and frustration. Along the journey, many people offered their great help and support me in various ways that I would like to acknowledge their presence. Firstly, I give my deepest thanks to my supervisor, Prof. Joseph Tak Fai Lau. He encourages, supports, and pushes me to achieve my full potential with every task, which has led to the completion of this final work. He has taught me how to become a mature researcher with his lessons on conceptualization. This important concept has made me a stronger and more motivated critical thinker. I am impressed by his enthusiasm, precision and creativeness in research. He has become a role model for me to follow. I am grateful for his mentorship, which I believe I will benefit from for the rest of my life. I would also like to thank Dr. Feng Tiejian, the director of Shenzhen Center for Chronic Disease Control, for his strong support in my fieldworks. I also deeply appreciate for the strong support from the directors of two other collaborative STD clinics, Dr. Wang Jing and Dr. Zhou Guomao. I would like to thank Dr. Xu Juan, Dr. He Qin, Dr. Chen Jiayuan, Dr. Li Qing, Dr. Xiang Li, Dr. Li Zhen, Dr. Yuan Jun, Dr. Liu Huan, Dr. Cai Yumao, Dr. Lai Yonghui, Dr. Qin Xiaolei, Dr. Cai Yuling, Mr. Xiong Cong, Mr. Wang Xifu, Mr. Huang Chengchao, Mr. Nuer Xiati, Mr. Chen Jiale, Ms. Yu Jia for their facilitating of my data collection. I thank all the participants for the cooperation. This study could not have been done without their help. VIII

11 I would like to thank Dr. Margaret Weeks from the Institute of Community Research in Hartford for her valuable suggestions. I would also like to thank Ms. Willa Dong and Ms. Danielle Walden for their help in editing this thesis. I would like to give my hearty thanks to Ms. Fang Yuan for her support and encouragement during all stages of the study. In addition, I deeply appreciate the help and support from my teammates: Prof. Gu Jing, Dr. Hao Chun, Dr. Li Haochu, Dr. Wu Xiaobing, Mrs. Li Chunrong and Mrs. Li Jinghua. I should also give my thanks to my classmates. Our friendship made this challenging journey quite enjoyable. The time with them will always be the golden memory of mine. Last but not least, I would like to thank my family member who gives me unwavering support and encouragement in the past three years. IX

12 Table of Content Abstract (English)... I Abstract (Chinese)... V Acknowledgement... VIII Table of Content... X List of Figures... XVII Abbreviation... XVIII Biography... XIX Chapter 1 Introduction Background The worsen HIV and STD epidemic in China The importance of male STD patients Male circumcision (MC) as an evidence-based HIV intervention MC implementation study Risk compensation as an important concern in MC promotion campaign Knowledge gap Lack of study investigating acceptability of MC among male STD patients in China Lack of study investigating factors associated with anticipated risk compensation Lack of MC implementation study among male STD patients in China Overall study design Aims Structure of the thesis Summary Chapter 2 Literature review HIV epidemic Global HIV/AIDS epidemic HIV epidemic in China Sexually transmitted diseases (STD) epidemic in China Syphilis epidemic in China Chlamydia epidemic in China Gonorrhea epidemic in China Genital herpes epidemic in China Genital warts epidemic in China STD prevention and control in China STD patients and HIV epidemic in China STD infection increases the risk of HIV infection Characteristics of male STD patients in China Prevalence of HIV among male STD patients in China Interventions targeting STD patients in China Male circumcision (MC) as an evidence-based bio-medical HIV/STD prevention X

13 2.4.1 Biological evidence Epidemiological evidence Prevalence of MC worldwide Acceptability of MC Factors associated with willingness to take up MC Risk compensation due to MC History of risk compensation and Risk Homeostasis Theory General examples of risk compensation Risk compensation in the area of HIV/STD Importance of risk compensation in MC promotion campaigns targeting heterosexual men Prevalence of risk compensation due to MC Factors associated with risk compensation due to MC Prevalence of anticipated risk compensation due to MC Factors associated with anticipated risk compensation due to MC Chapter 3 Participants and Methods Study design Study site Phase I: The cross-sectional MC acceptability and anticipated risk compensation study Participants Data collection Measures Phase II: a test-of-concept (TOC) trial promoting actual uptake of MC Participants Data collection Measurements Chapter 4 Description of the independent and dependent variables related to acceptability of MC and anticipated risk compensation due to MC Objectives Statistically analysis Results Socio-demographic characteristics of the participants STD/HIV related knowledge and services utilization STD history and sexual behavior Foreskin status of uncircumcised patients Frequency distribution of the two dependent variables Independent variables related to MC Independent variables related to anticipated risk compensation Discussion Chapter 5 Factors associated with conditional willingness to take up male circumcision (MC) Background Associations between background variables and willingness to take up MC XI

14 5.1.2 Associations between sexual risk behaviors and willingness to take up MC Associations between cognitive variables and willingness to take up MC Applying Health Behavior Theories to study willingness to take up MC Knowledge gaps Objectives Hypotheses Statistical analysis Results Associations between background variables and conditional willingness to take up MC Associations between cognitive factors and conditional willingness to take up MC Associations between emotional representation of STD infection and conditional willingness to take up MC Testing improvement in goodness-to-fit by adding subjective norm to the HBM-related variables Inter-relationship between emotional representation and cognitive variables on the association with conditional willingness to take up MC Discussion Chapter 6 Factors associated with anticipated risk compensation after taking up male circumcision (MC) Background History of risk compensation and Risk Homeostasis Theory Risk compensation in HIV/STD research Importance of risk compensation in MC promotion campaign targeting heterosexual men Knowledge gaps Objectives Hypotheses Statistical analysis Results Associations between background variables and anticipated risk compensation due to MC (compensation for >=1 type of risk behavior) Adjusted associated factors of anticipated risk compensation due to MC Inter-relationships among risk factors of anticipated risk compensation due to MC Interactive effect of degree of intention to take up MC on the associations between risk factors and anticipated risk compensation due to MC Discussion Chapter 7 The theory-based test-of-concept trial promoting MC Background Implementation study of MC for adult men Objectives Hypothesis XII

15 7.4 Methods Statistical analysis Results Comparing baseline characteristics between participants being followed up and those being loss to follow up for the telephone interview conducted at Month Prevalence of behaviors and intention related to MC during the 4-month follow up period Factors predicting adoption of MC during the 4-month follow-up period among all participants being followed up at Month Factors predicting adoption of MC during the follow-up period among participants who intended to take up MC at the baseline Results of the first telephone follow-up at Month 4 after intervention took place Results of the second telephone follow-up at Month 6 among participants who had taken up MC Characteristics of the participants who self-reported having and not having risk compensation behaviors after taking up MC (measured at Month 6 after intervention) Process evaluation - qualitative interviews with staff members of the participating STD clinics Discussion A potentially effective promotion program Strengths of our intervention Sustainability and opportunities for scaling up MC among male STD patients in China Possibility of promoting MC in other population Addressing the challenges Conclusion Chapter 8 Conclusions Recapitulation of key findings High acceptability of MC and associated factors A challenge - high prevalence of anticipated risk compensation due to MC and associated factors Good efficacy for the test-of-concept trial promoting MC Significance of this study Recommendations for scaling up MC Limitations of the study Overall conclusion References Appendix Appendix Appendix XIII

16 List of Tables Table 2.1 MC for HIV and STD prevention in men and their female sex partners Table 3.1 Samples of video scripts Table 3.2 Contents of the first and second telephone follow-ups Table 3.3 Content of the process evaluation Table 4.1 Background characteristics of the respondents Table 4.2 Frequency distribution of dependent variables (n=308) Table 4.3 Mean score of perceived HIV transmission risk, perceived risk reduction and perceived risk gap via one episode of sex with various types of female sex partners (n=308) Table 4.4 Frequency distribution of scores for perceived HIV transmission risk, perceived risk reduction and perceived risk gap via one episode of sex with various types of female sex partners (n=308) Table 4.5 Mean score of scales related to MC and anticipated risk compensation due to MC Table 4.6 Frequency distribution of cognitive variables derived from HBM and TPB among uncircumcised male STD patients (n=308) Table 4.7 Emotional representation of STD infection Table 4.8 Attitudes toward condom use among uncircumcised participants (n=308) Table 5.1 Background factors associated with conditional willingness to take up male circumcision Table 5.2 Associations between HBM-related variables and willingness to take up circumcision in the future six months Table 5.3 Association between subjective norm and conditional willingness to take up circumcision in the future six months Table 5.4 Association between emotional representation of STD infection and conditional willingness to take up circumcision in the future six months XIV

17 Table 5.5 Table 5.6 Table 5.7 Table 5.8 Table 5.9 Table 6.1 Table 6.2 Table 6.3 Table 6.4 Hierarchical logistic regression models using willingness to take up circumcision in the future six months conditional on HIV risk reduction and conditional on STD risk reduction as the dependent variables Testing interaction effects of emotional representation of STD infection with the associations between cognitive variables and willingness to take up MC in the future six months conditional on HIV risk reduction Testing interaction effects of emotional representation of STD infection with the associations between cognitive variables and willingness to take up MC in the future six months conditional on STD risk reduction Testing for independent effect of cognitive variables and emotional representation of STD infection on the associations with willingness to take up circumcision conditional on HIV risk reduction Testing for independent effect of cognitive variables and emotional representation of STD infection on the associations with willingness to take up circumcision conditional on STD risk reduction Associations between background variables and anticipated risk compensation due to MC (compensation for >=1 type of risk behavior) Associations between sexual behaviors and anticipated risk compensation due to MC (compensation for >=1 type of risk behavior) Associations between risk perceptions and anticipated risk compensation due to MC (compensation for >=1 type of risk behavior) Associations between attitudes toward condom use and anticipated risk compensation due to MC (compensation for >=1 type of risk behavior) XV

18 Table 6.5 Main effect and Mediation effects among risk factors of anticipated risk compensation (compensation for >=1 type of risk behavior) Table 6.6 Testing interactive effects of intention to take up MC for the association between risk factors and anticipated risk compensation (compensation for >=1 type of risk behavior) Table 7.1 Contents of the first and second telephone follow-ups Table 7.2 Content of the process evaluation Table 7.3 Characteristics of the participants Table 7.4 Background variables predicting taking up MC during the follow up among respondents being followed up in Month 4 (n=156) Table 7.5 Cognitive variables as predictors of taking up MC during the follow up among respondents being followed up in Month 4 (n=156) Table 7.6 Background variables predicting taking up MC during the follow up among respondents with initial intention at baseline (n=96) Table 7.7 Cognitive variables as predictors of actual taking up MC during the follow up period among respondents with initial intention at baseline (n=96) Table 7.8 Reasons for taking up during the follow up period (among participants who had taken up MC, n=31) Table 7.9 Reasons for not taking up MC despite initial intention (among those with behavioral intention at the baseline, measured at Month 4 follow up, n=68) Table 7.10 Reasons for not intending to take up in future (measured at Month 4 follow up, n=85) Table 7.11 Characteristics of participants who self-reported having and not having risk compensation behaviors after taking up MC (measured at Month 6 after intervention) XVI

19 List of Figures Figure 2.1 Number of people living with HIV worldwide Figure 2.2 Number of people newly infected with HIV worldwide Figure 2.3 (a) Flaccid uncircumcised penis. (b) Erect uncircumcised penis with the foreskin retracted showing likely sites of HIV-1 entry- 20 Figure 2.4 Prevalence of MC at country level, as of December Figure 3.1 Flow chart of Phase II test-of-concept trial Figure 6.1 Homeostasis mechanism (adapted from Wilde s risk homeostasis model) Figure 6.2 Potential relationships between perceived risk gap and risk compensation Figure 6.3 Potential effects of increasing condom use Figure 6.4 Graphical representation of the interaction effects between negative attitudes toward condom use and score of RGSPS on ln(odds) for anticipated risk compensation due to MC Figure 7.1 Flow chart of Phase II test-of-concept trial Figure 7.2 Prevalence of behaviors and intention during 4-month follow up XVII

20 Abbreviation AIDS AOR AHR ARR CDC CFSW CSM FSW HBM HIV HPV HR-HPV IDU MC MSM NRP OR PLWH PrEP RP TPB TSP UNAIDS WHO -2LL Acquired Immune Deficiency Syndrome Adjusted Odds Ratios Adjusted Hazard Ratios Adjusted Relative Risk Center for Disease Control and Prevention Clients of Female Sex Workers Common Sense Model Female Sex Worker Health Belief Model Human Immune Deficiency Syndrome Human Papillomavirus High Risk Human Papillomavirus Injective Drug User Male Circumcision Men Who Have Sex With Men Non-regular Female Sex Partner Odds Ratios People Living with HIV Pre-exposure Prophylaxis Regular Female Sex Partner Theory of Planned Behavior Target Set Point Joint United Nations Programme on HIV/AIDS World Health Organization -2XLog (likelihood) XVIII

21 Biography WANG Zixin Qualifications PhD candidate, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong Master of Medicine, School of Public Health, Peking University Health Science Center, Beijing, China Bachelor of Medicine, School of Public Health, Peking University Health Science Center, Beijing, China Awards : Global Scholarship Programme for Research Excellence CNOOC Grants for List of Publications Research papers 1 Wang Z, Lau JT, Gu J. Acceptability of male circumcision among clients of female sex worker in Hong Kong. AIDS Behav. 2012, 16(7): Wang Z, Lau JT, Hao C, Yang H, Huan X, Yan H, Guan W. Syphilis-related perception not associated with risk behaviors among men who have sex with men having regular male sex partner(s) in Nanjing, China. AIDS Care. 2013, 25(8): Wang Z, Lau JT, Lau M, Lai C. Acceptability of HPV vaccines and perceptions related to genital warts and penile/anal cancers among men who have sex with men in Hong Kong. Vaccine [Epub ahead of print]. 4 Lau JT, Wang Z, Lau M, Lai C. Perceptions of HPV, genital warts and penile/anal cancer and high risk sexual behaviors among men who have sex with men in Hong Kong. Arch Sex Behav Accepted in press. 5 Yu J, Li D, Wang Z*, Li C, Lau JT. Mental health status of men who have sex with men (MSM) in Beijing. Chinese Journal of STD and HIV. 2013, 19 (4): [Chinese] 6 Lau JT, Wang Z, Kim JH, Lau M, Lai C, Mo PKH. Acceptability of HPV vaccines and associations with perceptions related to HPV and HPV vaccines among men who have sex with men in Hong Kong. PLos ONE. 2013, 8(2):e XIX

22 7 Tsui HY, Lau JT, Wei X, Gu J, Wang Z. Should association between HIV-related risk perceptions and behaviors or intentions be positive or negative? PLoS ONE. 2012; 7(12): e You H, Lau JT, Gu J, Tsui HY, Wang Z, Kim JH. Awareness and acceptability of female condoms among monogamous Hong Kong Chinese female sexually transmitted infection patients. AIDS Behav. 2013, 17(3): Yan J, Lau JT, Tsui HY, Gu J, Wang Z. Prevalence and factors associated with condom use among Chinese Monogamous female patients with sexually transmitted infection in Hong Kong. J Sex Med. 2012;9(12): Lau JT, Yu X, Mak WW, Cheng Y, Lv Y, Zhang J, Su X, Wang Z. Prevalence of inconsistent condom use and associated factors among HIV discordant couples in a rural county in China. AIDS Behav. 2013, 17(5): Conference abstracts 1 Wang Z, Lau JT. Prevalence and associated factors of anticipated risk compensation after taking up male circumcision among heterosexual male sexually transmitted diseases patients in China. Poster presented at IAS 2013, Kuala Lumpur, Malaysia. Jun 30 to July 3, Wang Z, Lau JT, Li D. Repeated HIV voluntary counseling and testing increases risk behaviors among some men who have sex with men in China. Oral presented at XI International Conference AidsImpact to be held in BARCELONA, from September, 29th to October, 2nd, Lau JT, Wang Z. A two-phase acceptability and pilot implementation trial on male circumcision among male heterosexual sexually transmitted disease patients in China. Oral presented at XI International Conference AidsImpact to be held in BARCELONA, from September, 29th to October, 2nd, Lau JT, Wang Z, Lau M, Lai C, Mo PKH. Perceptions of HPV, genital warts and penile/anal cancer and high risk sexual behaviors among men who have sex with men in Hong Kong. Poster presentation at The Frontier of HIV/AIDS Research in China Biological and Behavioral Aspects, Washington DC, US, July 21, Lau JT, Hao C, Xu H, Gu J, Wang Z. Syphilis and HIV: Problems and opportunity. Oral presentation at the 15 th International Congress on Infectious Diseases, Bangkok, Thailand, June 9, Wang ZX, Lau JTF, Gu J. Acceptability of male circumcision and prevalence of anticipated risk compensation among clients of female sex worker in Hong Kong. Oral presentation at the International Conference on Global Health and Public Health Education, Hong Kong, from October Wang ZX, Lau JTF, Gu J. Acceptability of male circumcision among clients of female sex worker in Hong Kong. Oral presentation at the International Conference on Interdisciplinary HIV/STD Research in China, Guangzhou, from March 2011 XX

23 Chapter 1 Introduction 1.1 Background The worsen HIV and STD epidemic in China By the end of 2011, the number of people living with HIV (PLWH) in China was estimated to be 780,000, of whom 154,000 were living with AIDS [1]. In 2011, there were 48,000 reported new HIV cases in China. Heterosexual transmission was the major mode of transmission, The proportion of new HIV cases contributed to this mode was growing continually, from 42.2% in 2009 [2] to 52.2% in 2011 [1]. The epidemic of sexually transmitted diseases (STD) had been worsening and become a major public health issue in China [3]. The number of newly infected STD cases had rocketed up from 166 in 1981 to 119,955 in 2008 [4] The importance of male STD patients Male STD patients were of high risk of HIV infection and transmission. It was known that STD infection would increase the risk of HIV infection by many folds [5,6]. Many of them were clients of female sex workers (CFSW), previous studies reported 36.2% to 46.2% of them had frequently visited FSW in the last 3 months along with low prevalence of condom use during commercial sex (31.8% at the last sexual encounter with FSW) [7,8]. Meanwhile, 25.7% also self-reported had sex with at least one non-regular female sex partners (NRP, defined as a woman who was neither wife/regular girlfriend nor FSW) within three months with a low prevalence of condom use (30.1% at the last sexual encounter). As consistent condom use with regular sex partners (RP, defined as wife/regular girlfriend) was very low (5.5%) [7], they may form a bridge population transmitting HIV from high risk population (e.g. 1

24 FSW) to low risk population such as their spouses. Recent studies found that the prevalence of HIV among male STD patients ranged from 0.7% to 0.8% [7,8]. Such prevalence could be underestimated as very low percentage (6.2%-15%) of them had tested for HIV antibody before [7,8]. There are however, very few effective evidence-based interventions targeting high risk male heterosexual population (such as male STD patients) being implemented in China. Such interventions are greatly warranted Male circumcision (MC) as an evidence-based HIV intervention MC was an evidence-based biomedical HIV intervention recommended by WHO and UNAIDS. Three large-scale randomized control trials (RCT) on male circumcision (MC) conducted in Africa consistently showed that MC significantly reduced the risk of HIV-1 infection among heterosexual men by 53% to 60% [9,10,11]. A Cochrane review further supported its effectiveness [12]. In addition, MC could also prevent other STD infection (i.e. high-risk human papillomavirus (HR-HPV) infection [13,14], HSV-2 infection [13], syphilis infection [15] and Trichomonas vaginalis [16]). Furthermore, MC was not only male s issue as one trial reported derivative benefits for female partners of circumcised men: the risk of HR-HPV, bacterial vaginosis and trichomoniasis was reduced by 28%, 40% and 48% [17], respectively. However, MC was under-utilized in China. There was no history of routine circumcision and no norm promoting MC for Han majority population [18]. One previous survey indicated the prevalence of circumcision among male general population in China was less than 5% [19]. Acceptability study was important for designing effective intervention program. We can only find four studies investigating acceptability of male circumcision among male heterosexual 2

25 population in China (e.g. Yi minority [20], miners [21], male general population in western China [22] and CFSW in Hong Kong [23]). The prevalence of acceptability varied from 25.1% to 63.8% [20,21,22,23] MC implementation study There was a dearth of implementation study on MC among adult men in places other than Africa. We only found two studies published in Chinese and nil in English literature documented MC promotion among heterosexual adult male population outside Africa [24,25]. One of the studies targeted male community residents and another targeted miners in Guangxi province, China [24,25] and they used similar approaches. Intervention materials including education pamphlets and audio-visual materials were developed based on results of formative research, emphasizing that phimosis and redundant prepuce as the reasons for MC; HIV/STD risk reduction effects were also mentioned. A single-arm intervention using these materials was conducted in community setting by circumcised university students with medical background. In addition, participants received consultation from epidemiologists. As a result, the MC prevalence increased from 0% (baseline) to 12.7% (month 6) and 16.1% (month 9) in the community residents study and was 13.1 % at Month 9 in the miner study Risk compensation as an important concern in MC promotion campaign Risk compensation is the common psychological phenomenon of an increase in risk behaviors due to a decrease in perceived risk [26]. There was a concern that circumcised men may increase risky sexual behaviors due to real or perceived reduction of risk, which could lead to net increase in HIV risk exposure or 3

26 compromised the effectiveness for HIV prevention [27,28]. Risk compensation is hence an important issue in MC promotion campaign. Simulation studies suggested that risk compensation could reduce the impact of MC on reduction in HIV incidence [29,30,31] as one study suggested that impact of MC would be washed out if condom use reduced from 40% to 15% among newly circumcised men, or to 20% among all circumcised men [29]. Another study further suggested that moderate level of risk compensation (if men are ~60% less likely to use condom with casual partners after being circumcised), would lead to more HIV infection in women [31]. Risk compensation was considered as Achilles heel of campaigns promoting MC [32]. Therefore, it is very important to prevent risk compensation when launching MC promotion campaign. 1.2 Knowledge gap Lack of study investigating acceptability of MC among male STD patients in China Acceptability studies are important for designing effective intervention programs. However, there are only four recent studies on acceptability of MC conducted among heterosexual men in China (only two were published in English). None of them targeted male STD patients, a very high risk population of HIV infection and transmission in China. The result of our study could provide useful information in designing MC promotion campaign in this population. Heath behavioral theories are useful in explaining health-related behaviors. Only one study had applied some but not all constructs of HBM to explain willingness to take up MC [33]. Furthermore, that study was conducted among CFSW in Hong Kong instead of among high risk populations in mainland China. Moreover, HBM is 4

27 based on individual-level cognitive factors and this study also considered subjective norm, which is an interpersonal cognitive construct of TPB. Since emotional factors are also important, we hence included emotional representation of STD infection. The inter-relationships between the aforementioned variables were also studied. The result could therefore expand the scope of understanding factors associated with willingness to take up MC Lack of study investigating factors associated with anticipated risk compensation There was no study investigating anticipated risk compensation due to MC among male STD patients. The existing studies investigating factors associated with anticipated risk compensation due to MC mainly focused on socio-demographic characteristics and sexual behaviors, important component related to the Risk Homeostasis Theory, such as perceived risk gap, had not been investigated. Besides, some qualitative studies suggested that perceived risk reduction offered by MC is another potential factor associated with risk compensation due to MC. No study has quantified perceived risk reduction due to MC and investigated its association with anticipated or actual risk compensation due to MC. Risk Homeostasis Theory [26,34,35] specifies that people form a perception of risk level for performing a risky behavior that can potentially cause harm (e.g. unprotected sex and HIV). It is assumed that people usually feel comfortable with the risk associated with the behavior until it reaches a certain threshold, a level known as the Target Set Point (TSP). It was interesting to note that this theory has only mentioned situations that the perceived risk gap is negative (e.g. perceived risk for injury with helmet on may be lower than the TSP). That is not necessarily true for 5

28 those risk behaviors having relatively low TSP (i.e. having very severe outcome like that of HIV) which may implicate positive risk gaps. For instance, the perceived risk of unprotected sex with a HIV positive woman, assuming MC has taken place, could still be higher than the TSP. We contend that the theory can extend to also explain cases where risk gaps are positive in nature and that positive association between perceived risk gaps and lower risk compensation intention will be observed. Besides risk-related measures, other factors such as attitude toward condom use and previous sexual behaviors are also potential factors of anticipated risk compensation due to MC in our case. No study has looked at inter-relationships between such factors and the aforementioned factors related to risk perception Lack of MC implementation study among male STD patients in China The existing MC implementation studies were not based on behavioral theories and did not target high risk male populations [24,25]. Male STD patient population is an important population that can potentially benefit from the protective effect of MC because STD infection significantly increases the risk of HIV infection and their high prevalence of sexual risk behaviors. Previous MC implementation studies did not include process evaluation, which was an essential part of development and evaluation of successful interventions [36]. The sustainability of such intervention programs was hence unknown. Risk compensation, however, is an important issue need to be addressed in MC promotion campaign. However in previous studies, no information related to risk compensation was included in the intervention, and no measure of actual risk compensation was conducted during the follow up [24,25]. 6

29 1.3 Overall study design This two-phased study will firstly investigate acceptability and associated factors of MC as a means of HIV prevention among male heterosexual STD patients in China, and prevalence and associated factors of anticipated risk compensation due to MC using cross-sectional study design. Using such information, a single arm, non-blinded test-of-concept (TOC) trial was designed to promote actual taking up of MC in this study population. 1.4 Aims First of all, this study aimed to investigate the prevalence and associated factors of willingness to take up MC conditional on STD risk reduction and HIV risk reduction among uncircumcised male STD patients in Shenzhen, China. In this study, the associations between two dependent variables on conditional willingness to take up MC and background variables, cognitive variables (derived from HBM and TPB), and emotional variables were investigated. The inter-relationship between individual perceptions (HBM-related variables) and interpersonal perceptions (subjective norm), and between cognitive variables and emotional factors were also explored. Secondly, this study aimed to investigate the prevalence and associated factors of anticipated risk compensation due to MC among uncircumcised male STD patients in Shenzhen, China. Risk homeostasis theory was used to explain anticipated risk compensation due to MC for the first time. The associations between other independent variables (i.e. sexual behaviors, perceived risk reduction due to MC and attitudes toward condom use) and anticipated risk compensation were also investigated. Moreover, the inter-relationships between independent variables were 7

30 also explored. The interaction effect for degree of intention to take up MC on the association between risk factors and anticipated risk compensation were hence tested. In the test-of-concept trial, we aimed to assess the efficacy of the intervention developed based on the results of the acceptability study in promoting MC among eligible male STD patients. Besides, we investigated factors predicting MC taken up during the follow-up period. Specific reasons related to adoption of MC were also explored. Consequences of MC, including side effects of MC, risk perceptions, changes in sexual pleasure, sexual functioning and sexual behaviors after taking up MC were measured quantitatively. Attitudes and intentions related to risk compensation due to MC were assessed qualitatively. In addition, a process evaluation was conducted to evaluate the implementation process of the intervention, the feasibility and the sustainability of transforming the MC promotion into a regular service of the STD clinics. 1.5 Structure of the thesis Chapter 1 was an overview of the thesis, including the background, rationale, overall study design, aims and structure of the thesis. Chapter 2 provided a literature review on relevant topics of the thesis including the HIV epidemic worldwide and in China, and the worsen STD epidemic in China. Literatures on prevalence of sexual risk behaviors among male STD patients in China and interventions targeting this study population were then summarized. MC related topics, including biological evidence and epidemiological evidence of MC in 8

31 HIV and STD prevention, prevalence of MC worldwide and in China, acceptability of MC and associated factors, implementation study of MC were also introduced. Lastly, we had also reviewed the researches related to risk compensation, which was considered as important concern in MC promotion campaigns. Chapter 3 described the study participants and methods of this study. The study sites, participants, data collection and measurements of Phase I cross-sectional study and Phase II test-of-concept trial were introduced. Chapter 4 described the frequency distributions of the background variables, the two dependent variables in Phase I study (conditional willingness to take up MC and anticipated risk compensation due to MC), and various independent variables of these two dependent variables in detail. Chapter 5 investigated factors associated with conditional willingness to take up MC. The results provided a theoretical framework for designing an intervention promoting MC among the study population. Chapter 6 explored the factors associated with anticipated risk compensation due to MC. The results provided a comprehensive understanding of anticipated risk compensation due to MC, and had some implications for designing intervention in preventing risk compensation. Chapter 7 assessed the efficacy and sustainability of an intervention in promoting MC among male STD patients in STD clinic settings. The results indicated that MC 9

32 promotion among male STD patients is an important and promising health initiative. Recommendation for scaling up MC in STD clinic settings was provided. Chapter 8 was the conclusion section. Key findings of the thesis were summarized and interpreted. Significance of the study, recommendation for MC scaling up and limitations of this study were discussed. 1.6 Summary This study was one of the first implementing theory-based interventions promoting MC among male STD patients in China based on formative study in clinic setting. This study was also first applying Risk Homeostasis Theory in understanding anticipated risk compensation due to MC. The results of this study indicated MC promotion for male STD patients was feasible and sustainable in clinic settings. It also provided important information in designing effective intervention in preventing risk compensation due to MC, which was a critical issue needed to be addressed before MC was scaled up in this study population in China. Moreover, this study had enriched the health behavioral theories and Risk Homeostasis Theory, and provided some implication for further researches. 10

33 Chapter 2 Literature review 2.1 HIV epidemic Global HIV/AIDS epidemic UNAIDS (the Joint United Nations Programme on HIV/AIDS) estimated that there were 33.3 million (31.4 million~35.3 million) people living with HIV (PLWH) at the end of There was a 27% increase compared with a decade before (26.2 million in 1999) (Figure 2.1). The annual number of new HIV infections has been steadily declining since the late 1990s (Figure 2.2). It was estimated that 2.6 million (2.3 million~2.8 million) people were newly infected with HIV in 2009, which was ~20% lower than in 1997 [37]. Figure 2.1 Number of people living with HIV worldwide [37] Figure 2.2 Number of people newly infected with HIV worldwide [37] Sub-Saharan Africa remains the region most heavily affected by HIV, accounting for 67.6% of the PLWH (22.5 million) and 69.2% of the newly infected 11

34 cases (1.8 million), following by South and South-East Asia (4.1 million PLWH), North America (1.5 million PLWH) and Central and South America (1.4 million PLWH) [37]. The mode of HIV transmission varied in different regions. Heterosexual transmission was the predominated mode in Sub-Saharan Africa, Central and South America, the Caribbean and Oceania, while homosexual transmission was the driving force of epidemics of North America. Asia s epidemics remained largely among injective drug users (IDU), sex workers and their clients, and men who have sex with men (MSM). In Eastern Europe and Central Asia, where the largest regional increase in HIV prevalence was observed between 2001 to 2009, IDU had the highest HIV prevalence (37.0%~88.0%) [37] HIV epidemic in China By the end of 2011, the number of PLWH was estimated to be 780,000 (620,000~940,000), of whom 154,000 (146,000 ~ 162,000) were living with AIDS [1]. 46.5% of PLWH were infected through heterosexual sexual intercourse. It was estimated that 25% of the heterosexual transmission happened between married couples [1]. The overall prevalence of HIV was 0.058% (0.046% ~ 0.070%) for the total population; China therefore remained a low-prevalence country. In 2011, there were 48,000 new HIV cases reported in China. Heterosexual transmission was the major mode of transmission. The proportion of new HIV cases contributed to this mode was growing continually, from 42.2% in 2009 [2] to 52.2% in 2011 [1]. Respectively, 29.4%, 18% and 0.4% of the reported new HIV cases in 2011 were infected through homosexual transmission, injective drug use and mother-to-child transmission [1]. 12

35 2.2 Sexually transmitted diseases (STD) epidemic in China Sexually transmitted diseases (STD) has become a major public health issue in China as they re-emerged with the introduction of the open door policy and economic liberalization [3]. The STD epidemic in China progressed through four stages: 1) from 1977~1985, STDs were introduced from overseas to coastal cities, 2) during 1985~1988, STDs rapidly spread into inland cities, 3) during 1988 to 1992, the epidemic further spread from cities to villages and 4) from 1992 to now, the epidemic became extensive and severe [38]. In 1981, the number of newly infected STD cases was only 166. However, in 2008, the number of reported cases rocketed up to 119,955, with the incidence of /100,000 [4]. Five types of STD, including syphilis, chlamydia, gonorrhea, genital herpes and genital warts were included in the national surveillance system of China Syphilis epidemic in China The national surveillance data showed that the yearly reported syphilis cases had dramatically increased from 184 in 1985 to over 80,000 in ; after had slightly declined and stabilized below 80,000 for three years, the number had rocketed up to 395,182 in 2011 [39,40]. After remaining below 0.2 /100,000 for five years ( ), the overall incidence of syphilis increased from 0.17/100,000 in 1993 to 6.5/100,000 in 1999 [40]. After decreasing slightly between 2000 and 2003, the incidence increased again to as high as 21.06/100,000 in 2008 [4]. The prevalence of syphilis infection in different populations were: 0.4% for antenatal women, 0.7% for premarital individuals, 0.4% for voluntary blood donors, 2.9% for commercial blood donors, 0.8% to 12.5% among female sex workers 13