【作者】 蓝光华；

【导师】 梁浩；

【作者基本信息】 广西医科大学 ， 流行病与卫生统计学， 2011， 博士

【摘要】 第一部分:MSM人群HIV感染及其相关因素的基线调查目的深入了解南宁市男男性行为人群(men who have sex with men, MSM )人类免疫缺陷病毒(Human Immunodeficiency Virus, HIV)感染现状和相关影响因素,并初步了解MSM人群包皮环切术(Male Circumcision,MC)接受意愿的影响因素。方法通过滚雪球法在南宁市招募符合纳入标准的MSM 302人,进行一对一的问卷调查。问卷表内容包括人口学基本情况、性行为特征、包皮环切术情况、性病诊疗情况、吸毒情况、艾滋病防治知识态度等,并抽血检测HIV、梅毒、HSV-2(Herpes Simplex Virus-2,HSV-2)。结果(1)在302名研究对象中,平均男性性伴数中位数为3.5个,19.5%(59/302)与女性有过性关系。与男性发生性关系时每次都使用安全套的比例为46.1%(118/256),与女性发生性关系时每次都使用安全套的比例为28.8%(17/59)。(2) HIV阳性率为3.64%(11/302) ,梅毒阳性率为8.61%(26/302),HSV-2阳性率为12.25%(37/302)。(3)有12.3%(37/302)的人已接受过包皮环切术。未行包皮环切术者中有25.7%(68/265)愿意接受包皮环切术。(4)多因素回归分析结果显示,户籍、最近6个月肛交史与HIV感染有统计学意义(P≤0.05);包皮体检、最近6个月与女性发生过性关系与包皮环切术接受意愿有统计学差异(P≤0.05)。结论(1)南宁市MSM人群HIV、梅毒已有一定的流行水平,并有可能通过高频率的不安全性行为传染给其性伴/配偶。(2)不同的户籍和肛交史是影响南宁市MSM人群HIV感染的重要因素。(3)南宁市MSM人群包皮过长和与女性有过性关系者是包皮环切术接受意愿的重要影响因素。第二部分南宁市MSM队列随访分析目的通过对MSM人群进行随访,计算南宁市MSM人群HIV、梅毒、HSV-2新发感染率,探讨影响南宁市MSM队列保持率的相关因素,评估现有的艾滋病防治措施对南宁市MSM人群行为改变的影响,为南宁市MSM人群艾滋病预防策略和措施的制定和调整提供科学依据。方法在队列建立后为研究对象提供不定期的同伴教育、包皮环切术、强化咨询、安全套推广、转介等综合干预服务。分别在基线调查后的6个月和12个月对291名HIV阴性的MSM进行随访,随访内容包括人口学基本情况、性行为特征、包皮环切术情况、性病诊疗情况、吸毒情况、艾滋病防治知识态度以及HIV、梅毒、HSV-2检测。结果(1)新发感染率: 12个月随访时,HIV新发感染率为1.1/100人年(95%CI:0～3.3),梅毒新发感染率为6.8/100人年(95%CI:2.1～11.5),HSV-2新发感染率为5.2/100人年(95%CI:1.0～9.3)。(2)行为学改变:参加6个月随访的研究对象,男性性伴数与其在基线调查的结果比较,有统计学差异(P≤0.05);参加12个月随访的研究对象,男性性伴均数低于其在6个月随访的结果,二者比较有统计学意义(P≤0.05)。(3)包皮环切术情况:适合包皮环切术53人,手术比例为15%(8/53),并参加全程随访者有7人。(4)失访组和可随访组均衡性比较:人口学基本特征指标均没有统计学差异(P>0.05)。(5)队列保持的影响因素:多因素回归分析结果显示, 6个月能随访到(P=0.000,OR=12.597)、南宁市居住时间(P=0.044,OR=2.831)、最近六个月与女性发生过性关系(P=0.036,OR=5.359)是队列保持的独立影响因素。失访的主要原因是受访者电话答应回访但实际不回访和电话号码停用或变更。结论(1)南宁市MSM人群HIV/STD新发感染率低于全国其他地方报道。(2)队列人群的艾滋病高危行为有所改变,尤其是性伴数方面变化明显;安全套在男男性行为时使用率增加,但在异性性行为时基本无改变。(3)队列保持率较低,参加6个月随访、南宁市居住时间长、最近六个月与女性发生过性行为等是此次研究中影响队列保持的主要影响因素。第三部分MSM人群HIV感染的相关生物学因素的研究目的通过检测本次研究中发现的HIV感染者的HIV病毒载量、CD4+细胞计数、HIV基因亚型、TRL9和IFN-α表达水平,为南宁市和国家针对MSM人群的艾滋病防治工作提供相关的生物学数据。方法以基线和队列中发现的HIV感染者作为研究对象,通过生物梅里埃HIV-1病毒载量检测法(NucliSens EasyQ HIV-1)测定其HIV病毒载量;运用BD FACSCalibur流式细胞仪进行CD4+细胞计数检测;使用荧光定量PCR检测TLR9和IFN-α的表达水平;采用ABI3730测序仪对HIV-1基因亚型进行测序。结果(1)参加CD4+细胞计数检测有12人,其中200 cell/ul-350 cell/ul 7人,≥350 cell/ul 5人。参加病毒载量检测有17人,其中载量为500 cp/ml-3000 cp/ml 4人,3000 cp/ml-10000 cp/ml 2人,10000 cp/ml-30000 cp/ml 3人,大于30000 cp/ml以上8人。CD4+细胞计数和病毒载量无相关性(P>0.05)。(2) TLR9 CT在健康男学生和MSM HIV感染组分别为30.3±1.3、28.1±1.1;IFN-αCT在健康男学生和MSM HIV感染组分别为32.4±1.2、30.3±1.3,两组数值比较均无统计学意义(P>0.05)。(3)在14份HIV阳性的MSM血样中,HIV-1gag全长基因扩增出10份血样。经过系统树分析结果显示,属于CRF01—AE重组亚型9份,占90%,CRF07—BC重组亚型1份,占10%。结论(1) MSM HIV感染者CD4+细胞计数较低,病毒载量较高,出现艾滋病发病期,MSM人群HIV感染者发病的潜伏期缩短。(2) MSM HIV感染者的TRL9和IFN-α表达水平较低。(3)南宁市MSM人群感染的HIV主要为CRF01—AE重组亚型。更多还原

【Abstract】 Section one: The HIV infection rate and its influence factors in a baseline survey among MSM in Nanning cityObjective To investigate the HIV infection status and its influence factors among men who have sex with men (MSM) in Nanning. To determine the relative factors of the willingness of the male circumcision among MSM in Nanning. Methods 302 subjects were enrolled who were eligible for the inclusion criteria by the snowball method. The questionnaires were asked through face to face by the qualified trained investigators, the contents of questionnaire included basic demography, sexual behavior characteristics, Circumcision, sexually transmitted diseases clinic situation, drug abuse, AIDS knowledge, attitudes, etc. HIV, syphilis and HSV-2 were test. Results (1) The average number of male partners among MSM was 3.5. Who having sex with females accounted for 19.5%(59/302).The proportions of condom use each time in the course of sex with male and female were 46.1%(118/256)and 28.8%(17/59), respectively. (2) The positive rate of HIV, syphilis and HSV-2 were 364%(11/302), 8.61%(26/302) and 12.25%(37/302), respectively.(3) 12.3%(37/302)of them had circumcised. 25.7%(68/265) of the uncircumcised MSM were willing to accept circumcision. (4) In multiple regression analysis, census registration and the history of anal sex in the last 6 months were significantly associated with HIV infection(P≤0.05),The foreskin medical examination (OR = 2.63, 95% CI 1.93-3.58), the last six months had sexual relations with women (OR = 0.38,95% CI 0.16-0.91) were significantly associated with the willingness of circumcision(P≤0.05).Conclusions (1) The positive rate of HIV, syphilis and HSV-2 were high in MSM population in Nanning. The HIV/STD can be transmitted to their spouse and sex partners through MSM unprotected sex. (2) Census registration and the history of anal sex in the last 6 months were the influence factors of HIV infection among men who have sex with men (MSM) in Nanning. (3) Redundant prepuce and who had sexual relations with women in the last six months were willing to accept circumcision among MSM in Nanning.Section two: The analysis to the follow-up of the cohort of MSM in NanningObjective To determine the incidence of HIV, Syphilis and HSV-2 and the behavior change for the subjects during the follow-up, and investigate the influence factors of the cohort retention, for providing scientific evidence for the local government to develop and adjust the AIDS prevention strategies among MSM. Methods During the study, subjects were provided counseling, condoms and lubricants, volunteers, outreach services, circumcision, and referral services that are all free of charges. The follow-up visits were conducted in 6th month and 12th month. It included questionnaires and HIV, syphilis and HSV-2 tests. The questionnaire included basic demography, sexual behavior charac terist ics, circumcision, sexually transmitted diseases clinic situation, drug abu se, AIDS knowledge, attitudes, etc. Results (1) Of the 291 participants, the incidence rate was 1.1/100 person-years (95%CI:0～3.3) for HIV during the 12-month follow-up, 6.8/100 person-years (95%CI:2.1～11.5) for syphilis and 5.2/100 person-years (95%CI:1.0～9.3) for HSV-2. (2) The male sex partners were statistically significant among 6 month follow-up with relevant baseline and 12 month follow-up with relevant 6 month follow-up (P≤0.05). (3) Cohort of 53 persons for circumcision, the Circumcision rate was 15% (8/53), and 7 people can follow-up. (4) In the study, comparison of related variables between the group losing follow-up and the group of keeping to follow-up indicate that age, the history of receiving HIV test in the past year, the first partner and experiencing male commercial sex in the last 6 months have statistically significance(P≤0.05). (5) The main reason of withdrawal was persons in the cohort promised follow–up via phone calling but still failure in coming back, and phone numbers changed or stopped. In multiple regression analysis, follow-up in 6 month, reside time and female sex in the past 6 month were significantly associated with 12 month follow-up. Conclusions (1) Comparing with other cities in China, the incidence rate of HIV among MSM was low. (2) High-risk behaviors , especially the male sex partner had changed among the MSM cohort .The rate of condom use increased when had sex with male, but change little when had sex with female. (3) The retention rate was low. Follow-up in 6 month, reside time in Nanning and female sex in the past 6 month were significantly associated with 12 month follow-up in the study.Section three: The study of biological factors among MSM HIV infections in NanningObjective To test the HIV viral load, CD4+ lymphocyte count, HIV genotype and TRL9 and IFN-αexpression among the HIV infectors that discovered during the study, providing the biological data for MSM AIDS control. Methods HIV viral load was used the bioMérieux viral load way (NucliSens EasyQ HIV-1) to detect. CD4+ lymphocyte count by flow cytometry was used BD FACSCalibur. TLR9 and IFN-a was used fluorescence transcriptase cDNA quantitative polymerase chain reaction (PCR) to determinate. HIV-1 subtype was used ABI3730 sequencer to sequence. Results (1) 12 HIV infection MSM received CD4+ lymphocyte count test, including 7 people of 200cells/ul -350cells/ul and 5 people of≥350cells/ul. 17 HIV infection MSM participated in viral load test, including 4 people of 500 cp/ml-3000 cp/ml, 2 people of 3000cp/ml-10000cp/ml, 3 people of 10000 cp/ml-30000cp/ml and more than 8 people of over 30000cp/ml. CD4+lymphocyte count and viral load had no correlation(P>0.05). (2) TLR-9 CT in healthy male students and MSM HIV infected group were 30.3±1.3, 28.1±1.1, respectively. There are no significant difference between the two groups (P>0.05). IFN-αCT in healthy male students and MSM HIV infected group were 32.4±1.2, 30.3±1.3, respectively. There was no significant difference between the two groups (P>0.05). (3) In the 14 blood samples of HIV infected MSM, HIV-1gag full-length gene amplified from blood samples of 10, these 10 blood samples were sequenced. After a phylogenetic tree can be seen, subtype CRF01—AE is 9, accounting for 90%, subtype CRF07—BC is 1, accounting for 10%. Conclusions (1) In the HIV infected MSM, CD4+lymphocyte count was low and HIV viral load higher, HIV infection MSM Shorten the incubation AIDS period. (2) TRL9 and IFN-αexpression were low in HIV infection MSM. (3) Subtype CRF01—AE is the main HIV-1 subtype among MSM in Nanning .更多还原