不同高危險群的愛滋病毒感染者與有無共同感染疾病的病毒量及免疫動態變化探討

Dynamic Changes of Viral Load and Immunological Profiles in Different High Risk Groups of HIV-infected Individuals with versus without Co-infections

顏岑芳(Tsen-Fang Yen)

指導教授 ： 金傳春

國立臺灣大學/公共衛生學院/公共衛生碩士學位學程/碩士(2015年)

https://doi.org/10.6342/NTU.2015.11225

摘要

自1996年高效能抗愛滋病毒療法(highly active anti-retroviral therapy, HAART)藥物問世後，不僅有效改善愛滋病毒感染者的健康狀況、增加平均壽命及存活率，也降低大眾對愛滋病毒高致命性的擔憂。當患者健康狀況改善時，易降低戒心而出現無防護的危險性行為，造成其他性傳染病的感染或傳播，其中最常見的是梅毒。因此，本研究目的有三: (一)明瞭愛滋病毒的不同高危險群感染者之人口學等因素異同處，(二)探討梅毒菌、淋病菌、B型肝炎(B肝)病毒及C型肝炎(C肝)病毒等共同感染於愛滋病毒不同高危險群感染者的疾病盛行率與新發生率，及(三)探察梅毒共同感染是否會影響愛滋病毒感染者的免疫與病毒量的變化。
本研究以病歷回顧的回溯性研究，分析5,651位自2004年12月至2013年12月至臺北市某醫院就診的愛滋病毒帶原者，觀察於此研究期間罹患梅毒、淋病、B肝及C肝共同感染的盛行率，及新診斷梅毒與淋病的新發生率。另因本研究的愛滋病毒感染族群百分比、梅毒與淋病的盛行率，均以男男間性行為者居多(50.66%, 58.1%, 8.2%)，因此，續觀察691位於此九年研究期間被診斷為愛滋病毒感染，並於2012年至2013年間仍持續就醫的男男間性行為者，以配對T的統計檢定，比較感染梅毒前、後對愛滋病毒帶原者的CD3+ T細胞數、CD4+ T細胞數、CD8+ T細胞數及愛滋病毒量的影響。
於5,651位愛滋病毒帶原者的人口變項特性，發現以男性 [95.42%, (5,392/5,651)為大宗，而不同高危險群有近五成為男男間性行為者[50.66%, (2,863/5,651)]，其中以青壯年[80.93% (3,407/4,210), p<0.0001]、未婚[75.31% (4,256/5,651), p<0.0001]、有固定職業[74.22%, 4,194/5,651), p<0.0001]及曾受高等教育[ 50.45% (2,851/5,651), p<0.0001]者為主；且超過半數個案接受高效能抗愛滋病毒療法治療[ (54.26% (3,066/5651), p<0.0001]。比較CD4+ T細胞數低於200、350及500 cells/mm3分布，發現均以男男間性行為者最多[13.06% (374/5,651), p<0.0001; 42.93% (1,229/5,651) , p<0.0001; 71.11% (2,036/5,651) , p<0.0001]，其次為異性戀者[12.96% (74/5,651), p<0.0001; 38.70% (221/5,651), p<0.0001; 63.92% (365/5,651) , p<0.0001]。
愛滋病毒帶原者的梅毒、C肝、B肝及淋病之盛行率各為41.2%、30.5%、16.8%及5.2%。梅毒與淋病的發生率各為每100人年8.58例與1.59例，兩者發生率近年均有上升趨勢；另比較兩共同感染於不同高危險群的發生率，發現仍以男男間性行為者為主，其在兩性傳染病發生率分別為每100人年10.48例及2.21例。
比較男男間性行為兩群感染愛滋病毒有無抗愛滋病毒治療後續再感染梅毒前、後兩時間點的CD3+ T細胞、CD4+ T細胞與CD8+ T細胞的變化，發現於(A)36例感染愛滋病毒0-3年且未受高效能抗愛滋病毒療法治療者，在梅毒共同感染後均會統計顯著降低CD3+ T細胞、CD4+ T細胞與CD8+ T細胞的平均值(感染梅毒前、後的CD3+ T: 1,785.6 ± 569.2 vs 1,578.2 ± 624.6, p=0.044; CD4+ T: 522.3 ± 189.8 vs 438.2 ± 176.1, p=0.003; CD8+ T: 1,172.8 ± 472.4 vs 1,074.4 ± 524.8, p=0.039：各降低了207.4 cells/mm3, 84.1 cells/mm3, 98.4 cells/mm3)；另於(B) 46例感染愛滋病毒3-8年且以高效能抗愛滋病毒療法治療者，在梅毒共同感染後亦會統計顯著降低CD3+ T細胞、CD4+ T細胞與CD8+ T細胞的平均數值(CD3+ T: 1,769.3 ± 623.7 vs 1,589.0 ± 520.4, p=0.008; CD4+ T: 632.1 ± 239.9 vs. 574.9 ± 191.8, p=0.020; CD8+ T: 1,031.9 ± 455.9 vs. 933.5 ± 420.0, p=0.0.18：但降量較(A)群為低，各降低了180.3 cells/mm3, 57.2 cells/mm3, 98.4 cells/mm3)。
比較男男間性行為者感染梅毒前、後的愛滋病毒量變化，發現無論愛滋病毒感染時間長(3-8年)、短(0-3年)或是有、無接受抗愛滋病毒治療，其愛滋病毒量變化雖無統計差異，但發現其於共同感染梅毒時，均增愛滋病毒量[於(A) 感染愛滋病毒3-8年且無抗此病毒治療者在感染梅毒前、後的愛滋病毒負荷量各為: 63,094.8 ± 69,305.0 vs 211,546.0 ± 402,970.0 RNA copies/ml, p=0.350;增愛滋病毒量148,451.2 RNA copies/ml；(B)感染愛滋病毒0-3年且未受抗此病毒療法治療者，在感染梅毒前、後的愛滋病毒量各為: 42,788.1 ± 56,160.4 vs 43,474.5 ± 39,290.2 RNA copies/ml, p=0.944，增愛滋病毒量686.4 RNA copies/ml； (C)感染愛滋病毒0-3年且有受抗此病毒療法治療者，在感染梅毒前、後的愛滋病毒負荷量各為: 191.9 ± 336.9 vs 1,999.0 ± 6217.8 RNA copies/ml, p=0.380; 增愛滋病毒量1,807.1 copies/ml]，即愛滋病毒帶原者於不接受高效能抗愛滋病毒療法治療時，梅毒共同感染更會增其愛滋病毒量。
綜合此研究結果，發現愛滋病毒帶原者共同感染梅毒時，均會顯著地降低CD3+ T細胞、CD4+ T細胞與CD8+ T細胞數。然近年來我國愛滋病毒帶原者通報數逐年上升，又有年輕化趨勢，且合併共同感染的盛行率居高不下。因此，建議第一線醫療人員於照護愛滋病毒帶原者時，應提醒其注意安全性行為的重要性，避免其他共同感染影響自身免疫而增發病或死亡風險。建議政府相關防疫單位，未來應考慮對性傳染病患者推動整合性的防疫作為，自偵測系統至流行病學數據分析、醫護人員對患者的衛生教育、民眾的自覺與防制作為及防疫作為的定期評估等等。

關鍵字

愛滋病毒感染流行病學 ； 共同感染疾病 ； 梅毒 ； 淋病 ； B型肝炎帶原 ； C型肝炎病毒感染 ； 輔助型T細胞(CD4+ T cells) ； 毒殺型T細胞(CD8+ T cells) ； 臺灣

並列摘要

HIV-infected individuals have not only increased the average life expectancy and survival rates, but also reduced the public concerns on high fatality of HIV virus after the highly active anti-retroviral therapy (HAART) was available since 1996. However, unprotected sex has lead to the spread of other sexually transmitted diseases (STDs), including syphilis - the most common STD, when patients get better. Therefore, this study had three specific aims: (1) to understand the similarities and differences in demographical and other variables among different HIV-(+) risk groups, (2) to investigate the prevalence and incidence rates of the coinfections of HIV and the other four infections, including Treponema pallidum, Neisseria gonorrhoeae, hepatitis B virus (hepatitis B surface antigen, HBsAg) and hepatitis C (anti-HCV) in different high-risk groups of HIV infection, and (3) to examine whether the co-infection of HIV and syphilis might affect immunity and viral load in HIV-(+) individuals .
Using a retrospective chart review study, we analyzed 5,651 HIV-carriers visited Taipei City Hospital-X from December 2004 to December 2013. The prevalence rates of the co-infection of HIV and syphilis, gonorrhea, hepatitis B, and hepatitis C, as well as the incidence rates of the two newly diagnosed STDs (syphilis and gonorrhea) were measured. We then focused on 691 HIV-(+) men sex with men (MSM) continued to visit the hospital-X in 2012-2013 because this risk group had the highest HIV-(+), syphilis-(+) and Gonorrhea-(+) infections (50.66%, 58.1%, 8.2%, respectively). The paired T-test was used to compare the differences in the absolute counts of CD3+ T cells, CD4+ T cells, CD8+ T cells and the levels of HIV viral load in HIV carriers after the co-infection of syphilis.
Analyzing the demographical characteristics of 5,651 HIV (+)-carriers, we found that males accounted for the most [95.42% (5,392 /5,651), p<0.0001). Comparison of different high-risk groups, MSM ranked the highest [50.66% (2,863 / 5,651), p<0.0001], of which the young and middle-aged [80.93% (3,407 / 4,210), p<0.0001], unmarried [75.31% (4,256 / 5,651), p<0.0001), having an occupation [74.22% (4,194 / 5,651), p<0.0001], and receiving higher education [50.45% (2,851 / 5,651), p<0.0001] were the majority. More than half of the cases had received HAART [54.26% (3,066 / 5651), p<0.0001]. In addition, MSM had the highest numbers of their CD4+ T cell counts below 200, 350 and 500 cells/mm3 [13.06 % (374 / 5,651) , p<0.0001; 42.93% (1,229 / 5,651) , p<0.0001; 71.11% (2,036 / 5,651) , p<0.0001, respectively], followed by heterosexual [12.96%, (74/5651) , p<0.0001; 38.70% (221 / 5,651) , p<0.0001; 63.92% (365 / 5,651), p<0.0001, respectively].
The prevalence rates of the coinfections of HIV with syphilis, hepatitis C, hepatitis B and gonorrhea, were 41.2%, 30.5%, 16.8% and 5.2%. The incidence rates of syphilis and gonorrhea were 8.58 and 1.59 cases per 100 person-years. Both of which increased in recent years and MSM ranked the highest for both of these two co-infections, with the incidence rates of 10.48 and 2.21 cases per 100 person-years.
Comparing the changes of T cell counts before and after the co-infection of syphilis among HIV-(+) MSM with or without HAART treatment in MSM, we analyzed the following two groups. (A) The means of CD3+ T cells, CD4+ T cells, CD8+ T cells absolute values were significantly reduced after the 36 cases with the co-infection of syphilis in HIV-(+) carriers for 0-3 years without HAART treatment (before and after infection with syphilis in CD3+ T: 1,785.6 ± 569.2 vs 1,578.2 ± 624.6, p=0.044; CD4+ T: 522.3 ± 189.8 vs 438.2 ± 176.1, p=0.003; CD8+ T: 1,172.8 ± 472.4 vs 1,074.4 ± 524.8, p=0.039 : each decreased 207.4 cells/mm3, 84.1 cells/mm3, 98.4 cells/mm3, respectively). (B) The means of CD3+ T cells, CD4+ T cells, CD8+ T cells absolute values were significantly reduced after the 46 cases with the co-infection of syphilis in HIV-(+) carriers for 3-8 years with HAART treatment (before and after infection with syphilis in CD3+ T: 1,769.3 ± 623.7 vs 1,589.0 ± 520.4, p=0.008; CD4+ T: 632.1 ± 239.9 vs 574.9 ± 191.8, p=0.020; CD8+ T: 1,031.9 ± 455.9 vs 933.5 ± 420.0, p=0.0.18: but the decreasing numbers were lower than (A) group, with the reduction of 180.3 cells/mm3, 57.2 cells/mm3, 98.4 cells/mm3, respectively).
On the other hand, MSM with co-infections of HIV-(+) and syphilis all increased the levels of HIV-viral load in the following three groups, regardless of short or long duration of HIV-infection, with or without receiving HAART, although there were no statistical differences. (A) HIV infection for 3-8 years but without HAART prior to the infection with syphilis [HIV viral load before and after syphilis (HIV-VL BeAf-Sy): 63,094.8 ± 69,305.0 vs 211,546.0 ± 402,970.0 RNA copies/ml, p=0.350; increased HIV 148,451.2 RNA copies/ml]. (B) HIV infection for 0-3 years but without HAART prior to the infection with syphilis [HIV-VL BeAf-Sy: 42,788.1 ± 56,160.4 vs 43,474.5 ± 39,290.2 RNA copies/ml, p=0.944, increased HIV 686.4 RNA copies/ml]. (C) HIV infection for 0-3 years and receiving HAART prior to the infection with syphilis [HIV-VL BeAf-Sy: 191.9 ± 336.9 vs 1,999.0 ± 6217.8 RNA copies/ml, p=0.380; increased HIV 1,807.1 RNA copies/ml. In other word, co-infection of syphilis after HIV did increase HIV-viral load, particularly for those who had not received HAART.
In conclusion, HIV carriers co-infected with syphilis resulted in decreasing the absolute counts of CD3+ T cells, CD4+ T cells, CD8+ T cells. As the reported case numbers of HIV carriers increased and these HIV-(+) individuals getting younger, and prevalence rates of the co-infections of HIV and other STDs have remained high in recent years, we offer the following recommendations. (1) Those health care workers who are in the first-line caring for HIV carriers, should remind these individuals the importance of safe sex to prevent other co-infections’ altering immunity and thus increasing the risk of diseases onset and deaths. (2) For STD-infected persons, integrated prevention and control measures from surveillance system to epidemiological data analysis, health education, and self alertness should be implemented and regularly evaluated in government agencies.

並列關鍵字

HIV ； co-infections ； syphilis ； gonorrhea ； hepatitis B carrier ； hepatitis C virus infection ； CD4+ T cell ； CD8+ T cell ； Taiwan

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