一個老問題的新面貌

資料來源：剌胳針感染症醫學期刊；www.thelancet.com/infection Vol 17 December 2017；

財團法人台灣紅絲帶基金會編譯

愛滋病毒感染的發生率十年沒有變化。自2005年以來，每年約有260萬人新感染愛滋病毒。年輕婦女，特別是少女，在愛滋病毒新感染比率上更佔不成比例的高。制定預防愛滋病毒的成功策略可能需要更多創造性的方法以滿足最易受影響人群的需求，包括去探索性感染症如單純皰疹病毒2型（HSV-2）在愛滋病毒感染上的角色。

單純皰疹病毒2型( HSV-2 ) 的感染對愛滋病毒的高發生率具有貢獻 ；有證據顯示HSV-2感染增加愛滋病毒感染的風險，在「剌胳針感染症」醫學期刊中，Katharine Looker和同事提供了十多年來第一次的系統回顧和整合分析（meta-analysis［註1］，到2017年5月）評估HSV-2的感染對隨後的HIV感染的影響，他們分析了57項縱貫性的研究並得出普遍盛行或偶然的HSV-2感染與HIV感染關係的匯總隨機效應估計值。他們對普遍盛行的HSV-2感染的發現與先前的研究之數據一致，並顯示愛滋病毒感染風險在一般人群中大約為三倍，而在高風險人群中幾乎為二倍。他們匯總的估計值在偶然的HSV-2感染對HIV感染的影響上，顯示偶然的HSV-2感染對HIV感染的關聯在一般人群中其愛滋感染風險增加達五倍，而在高危人群中愛滋感染風險則增加達三倍。

在2012年對HSV-2感染的估計值強調了這一問題的嚴重性，對非洲的婦女和女孩則特別嚴重。在2012年全球的HSV-2的感染者約有4.17億人，其中女性佔感染者的64％。雖然感染HSV-2的女性只有四分之一為15-24歲年齡層，但三分之二的新感染來自這個年齡層，顯示政策回應應專注於年輕女性和青春期少女上。在2012年，估計在非洲15-49歲女性人群中其HSV-2感染的盛行率為38％。大約有1.35億15-49歲的非洲人感染了HSV-2；其中 2,240萬為15-24歲的女性。另外非洲有640萬個HSV-2新感個案；其中有230萬個是15-24歲的女性。這些數字特別令人擔憂，因為在2015年15至24歲的非洲婦女其愛滋病毒的新感人數在所有年齡層中人數是最多的。

在高HSV-2盛行率的人群中減輕愛滋病風險的策略已被探索。一項策略檢測使用acyclovir（400毫克每天兩次）［註2］來對HSV-2作抑制治療是否可以降低愛滋病毒風險，來自兩項研究的數據，顯示了acyclovir在HSV-2感染者身上沒有降低HIV的發生率。另一項研究則針對沒有服用抗反轉錄病毒藥物之愛滋病毒和HSV-2共病的感染者，與他們可能有或可能沒有感染過HSV-2的愛滋病毒陰性伴侶，評估了acyclovir對愛滋病毒傳播的影響。儘管於二種疾病共病的伴侶身上在HIV病毒載量和生殖器潰瘍的頻率上有所減少，但每日acyclovir治療並沒有減少愛滋病毒傳播的風險。提供多用途預防技術來對HSV-2、HIV或兩者的暴露前預防是另一種選擇。來自南非針對889名婦女之CAPRISA 004 HIV預防試驗的數據顯示，於陰道應用1％ tenofovir［註3］凝膠減少HIV感染率為39％，出乎意料的是HSV-2的感染亦減少51％。隨後的第3期試驗則顯示凝膠對可能的愛滋病毒感染並沒有效果，歸因於對研究產品的低順從性。口服的舒發泰（Truvada， emtricitabine-tenofovir）適用於暴露前預防可降低在高危成人中透過性行為感染HIV的風險。雖然舒發泰沒有適用於HSV-2，在HIV-1陰性的異性戀男性而其伴侶為HIV-1和HSV-2合併感染的女性伴侶中，舒發泰減少了這些男性HSV-2的感染達33％。但是，對於處在所有風險的個體中（HIV，HSV-2，或HIV以及HSV-2）舒發泰不是一項選擇，因為它在非洲撒哈拉沙漠以南和其他低收入地區的可獲性很差，使用者的接受度和順從性問題，以及對抗HSV-2的適度療效等因素。

因此，其他針對HSV-2和HIV的多用途預防技術，需要給予個案一系列廣泛的預防選擇，並針對最易感人群的偏好和生活方式，更應包括在全球中其HIV和HSV-2的發生率最高的非洲年輕女性。

註1：meta-analysis，整合分析『或稱「後設分析」、「薈萃分析」是一種運用統計技術，綜合先前獨立執行研究之結果的一種評述程序。整合分析為了統整發現，先大量蒐集個別研究的分析結果，再作統計分析，以尋求一般性結論的技術；具有對研究因果關係、敘述的討論，提出替代性處理，以便能擴充研究文獻的意義』。

註2：Acyclovir，阿昔洛韋又被寫作（Aciclovir，ACV）或Acycloguanosine，又稱無環鳥苷，是一種鳥嘌呤類似物類的抗病毒藥物。阿昔洛韋是最常用的抗病毒藥物之一，主要用於治療單純皰疹病毒感染，也可用於水痘、帶狀皰疹的治療。另外也應用在移植手術後，預防人類皰疹病毒第四型等巨細胞病毒感染的預防性投藥。同時具有口服劑型與靜脈注射劑型。

註3：Tenofovir，替諾福韋，商品名韋瑞德（英語：Viread）或其它，是一種用於治療慢性B肝以及預防和治療HIV感染/愛滋病的藥物。這種藥物屬於反轉錄酶抑制劑，可以抑制HIV病毒的複製。替諾福韋可用於預防高危人群感染HIV，但藥物不能治癒HIV/AIDS或B肝。

A fresh look at an old problem

The incidence of HIV infection has not changed in a decade. Since 2005, about 2·6 million people have

become newly infected with HIV annually. Young women, particularly adolescent girls, account for a disproportionate number of new HIV infections. Development of successful strategies to prevent HIV

acquisition might require more creative approaches to meet the needs of the most susceptible populations,

including exploration of the role of sexually transmitted infections, such as herpes simplex virus type 2 (HSV-2), in HIV infection.

HSV-2 contributes to the high incidence of HIV; evidence has shown that HSV-2 infection increases the risk of HIV infection. In The Lancet Infectious Diseases, Katharine Looker and colleagues provide the first systematic review and meta-analysis (to May 2017) in over a decade to assess the effect of HSV-2 infection on subsequent HIV acquisition. They analysed 57 longitudinal studies and derived pooled random-effect estimates of the association between prevalent or incident HSV-2 infection and HIV acquisition. Their findings for prevalent HSV-2 infection were in line with data from previous studies and showed that the risk of HIV acquisition was roughly tripled in general populations and almost doubled in high-risk populations. Their pooled estimates for the effect of incident HSV-2 infection on HIV infection showed that incident HSV-2 infection was associated with a five times increase in the risk of HIV in general populations and a three times increase in the risk of HIV in high-risk populations.

Estimates for HSV-2 infection in 2012 underscored the magnitude of the problem, which was particularly serious for women and girls in Africa. About 417 million people were living with HSV-2 worldwide in 2012, with women accounting for 64% of infected individuals. Although only a quarter of women infected with HSV-2 were aged 15–24 years, two-thirds of new infections came from this age group, suggesting that policy responses must focus on young women and adolescent girls. In 2012, the estimated overall prevalence of HSV-2 infection in African women aged 15–49 years was 38%. About 135 million people in Africa aged 15–49 years were infected with HSV-2; 22.4 million were women aged 15–24 years. Another 6.4 million people in Africa were newly infected with HSV-2; 2.3 million were women aged 15–24 years. These numbers are particularly concerning because women in Africa aged 15–24 years had the highest number of new HIV infections of all age groups in 2015.

Strategies to mitigate the risk of HIV in populations with a high HSV-2 prevalence have been explored. One strategy tested whether HSV-2 suppressive therapy with acyclovir (400 mg twice per day) could reduce the risk of HIV. Data from two studies showed that acyclovir did not decrease the incidence of HIV in HSV-2 infected individuals. Another study assessed the effect of acyclovir on HIV transmission from a person coinfected with HIV and HSV-2 who was not on antiretrovirals to a partner who was HIV negative and who might or might not have been infected with HSV-2. Despite a decrease in HIV viral loads and frequency of genital ulcers in the coinfected partner, daily acyclovir therapy did not reduce the risk of HIV transmission. A multipurpose prevention technology that provides pre-exposure prophylaxis for HSV-2, HIV, or both is another option. Data from the CAPRISA 004 HIV prevention trial of 889 women in South Africa showed that vaginally applied 1% tenofovir gel reduced HIV infection by 39% and, unexpectedly, HSV-2 infection by 51%. Subsequent phase 3 trials showed that the gel was not effective against HIV acquisition, which might be attributed to low adherence to the study products. Oral emtricitabine-tenofovir (Truvada) is indicated for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV infection in high-risk adults. Although not indicated for HSV-2, Truvada reduced HSV-2 acquisition in heterosexual men who were HIV-1 negative and in women with HIV-1 and HSV-2 coinfected partners by 33%. However, Truvada is not an option for all at-risk (HIV, HSV-2, or HIV and HSV-2) individuals because of its poor availability in sub-Saharan Africa and other low-income regions, user acceptability and adherence issues, and modest efficacy against