為什麼愛滋病毒爆發流行會重現於注射藥癮者當中?

 

為什麼愛滋病毒爆發流行會重現於注射藥癮者當中?

資料來源:刺胳針愛滋病毒醫學雜誌,線上發表,201949日;財團法人台灣紅絲帶基金會編譯

    2015年,在蘇格蘭的大格拉斯哥和克萊德地區目睹了注射藥癮者(PWID)爆發了愛滋病毒感染。這一事件有兩個特別罕見的原因:這是自20世紀80年代以來,於蘇格蘭在注射藥癮者中第一次的愛滋病毒流行,並且發生在針頭和針具之供應具有高覆蓋率以及在阿片類藥物替代治療計劃正實施的環境中。

   格拉斯哥的疫情是自2011年以來於歐洲和世界範圍內,在注射藥癮者當中所報告的一系列愛滋流行疫情之一。1980年至1990年代期間在西歐幾個城市(包括蘇格蘭的愛丁堡和鄧迪)所發生早期的流行後,經迅速採取了減害措施,且似乎多年來在避免爆發流行方面上取得了成功。 2011年,希臘的雅典和羅馬尼亞的布加勒斯特的注射藥癮者報告了兩次愛滋病毒爆發流行。從那時起,歐洲、北美和中東出現了更多的流行:包括以色列的特拉維夫(2012年)、盧森堡(2013年)、愛爾蘭的都柏林(2014年)、美國侈印第安納州(2014年),以及加拿大的薩斯喀徹溫省(2016年)。

在剌胳針愛滋病毒雜誌中,Andrew McAuley及其同事報導了格拉斯哥於2015年爆發的情況。他們的文章強調了在低閾值的環境中生物-行為監測方法,用於監測血液傳播病毒和風險行為上的價值,從而識別出爆發流行並確定其病因。他們利用2011-18針具交換監測計畫(NESI)調查的數據,針對注射藥癮者參加提供注射設施服務的一系列國家之橫斷式生物-行為調查,作者評估了造成愛滋病毒感染的個人和環境上的風險因素。在他們的最終模型中,McAuley及其同事發現,愛滋病毒感染與近期古柯鹼的注射史有密切相關(調整後的勝箅比為6.795%信賴區間為 3.8 - 12.1)或經歷過無家可歸者(3.0 1.7 - 5.0)。作者將格拉斯哥的疫情歸因於無家可歸者的增加;共用注射用具,反映在愛滋病毒感染者中高的C型肝炎盛行率;對愛滋病風險的認識欠佳;以及古柯鹼注射的增加等等因素。

古柯鹼使用的增加趨勢並不是局部現象。近年來,歐洲藥物市場中高純度古柯鹼的供應量激增,導致古柯鹼成為許多吸毒者首選的興奮劑。古柯鹼注射的增加似乎也在盧森堡注射藥癮者的愛滋病毒爆發流行中發揮了一定角色。

 無家可歸者在愛滋病毒傳播中的作用已經在格拉斯哥以及在都柏林和雅典爆發流行時發現,為什麼無家可歸的注射藥癮者即使在調整了高風險行為之後,也面臨更高的愛滋病風險?有些人認為無家可歸的注射藥癮者,更有可能是大型注射網絡中具連結成員的核心。如果一個或多個成員被感染,該核心有可能成為HIV傳播的中心。

McAuley及其同事發現女性注射藥癮者的風險非顯著性的增加(調整後的勝算比為1.795%信賴區間為 0.9 - 3.2p = 0.083),這表明在女性中性傳播可能導致HIV的感染。女性注射藥癮者的性傳播在雅典暴發流行期間,由女性性伴侶之數量與愛滋病風險間的關聯中得到了證實,而男性則沒有。儘管McAuley及其同事的結果證據不足,但這一發現值得注意的是,在都柏林和盧森堡的愛滋病毒爆發流行中,婦女尤其受到影響。

一個有趣的問題是,為什麼在格拉斯哥全面實施減害計畫的環境背景下,30年來第一次發生愛滋病毒的爆發流行。即使在具有高覆蓋率的針頭和針具計畫的環境中,也不可避免地存在注射藥癮者在注射器的獲取上並不充分;在2011-16的調查中,15-33%的參與者報告在過去6個月內其注射器覆蓋率低於100%。這一比例可能被低估,因為樣本係來自參加供應注射設施服務的注射藥癮者。假設減害服務的覆蓋範圍隨著時間的推移而保持穩定,儘管如此問題仍然存在:是什麼觸發了傳播?無家可歸者這一種經常被發現的危險因素,在蘇格蘭於2000年後增加,並在2010 - 11年之前維持在較高的水平中。來自格拉斯哥爆發流行由系統發生學上HIV序列的分析顯示,有效繁殖數量(即來自每個個體的繼發性HIV感染的平均數量)在同一時期增加,並在2009年達到頂峰。無家可歸者的增加可能導致網絡凝聚力的變化(即,在注射藥癮者網絡內的連結性)。即使風險行為隨著時間的推移保持穩定,網絡凝聚力的變化也可能解釋了傳播的增加。因此,當HIV被引進入具高度互聯的無家可歸者網絡中,兼以共用注射用具,可能激發了疫情爆發。此外,古柯鹼使用上的增加更可能導致採取更高水平的愛滋風險行為並擴大傳播之流行。

與雅典和布加勒斯特的疫情相比,格拉斯哥疫情的規模相對較小。然而,另一個有趣的問題是,為什麼愛滋病毒在格拉斯哥的傳播持續時間超過3年,儘管提供多層面的應對措施,包括對已感染愛滋病毒的注射藥癮者強化治療之連結、對處於風險者提供愛滋病毒教育、增加檢驗、和改善注射設施之供應等措施。然而這種方法可能無法足夠快速地達到那些最需要幫助的人身上。由此波流行在二次傳播高峰後6年仍被確認的事實上顯示,可能有一個注射藥癮者次群體並無法獲得他們可以接受診斷並連結治療等相關的服務。以社區為基礎的方法採用同儕導引鏈結之轉介,例如在雅典爆發流行時採用的ARISTOTLE計劃,以尋找、檢驗和治療注射藥癮者為策略,有助於提高對注射藥癮者網絡的滲透率,並快速接觸到那些最有可能感染愛滋病毒的人

格拉斯哥疫情以及最近在注射藥癮者當中爆發的其他流行疫情,突顯了這一人口群對經濟、社會和藥物市場變化上易受傷害的程度,以及在預防愛滋病毒爆發之介入措施其成功方面的脆弱程度。高覆蓋率的減害計畫應奠基於社區計畫並與愛滋病毒感染和相關行為之監測相結合,努力去觸及那些接受服務水平最低的人群,並迅速應對潛在的威脅。

作者:Vana Sypsa,雅典國立卡波迪斯特拉大學醫學院,衛生、流病和醫學統計系,雅典,希臘。

Why do HIV outbreaks re-emerge among people who inject drugs?

Published Online; April 9, 2019  www.thelancet.com/hiv Vol 6 May 2019

2015 witnessed an outbreak of HIV infection among people who inject drugs (PWID) in the Greater Glasgow and Clyde area of Scotland. There are two reasons why this incident is particularly exceptional: it was the first HIV epidemic among PWID in Scotland since the 1980s and it occurred in a setting where high-coverage needle and syringe provision as well as opioid substitution treatment programmes were implemented.

The Glasgow outbreak is one of a series of HIV epidemics reported among PWID in Europe and worldwide since 2011. After the early epidemics in the 198090s in several cities in western Europe, including Edinburgh and Dundee in Scotland, harm reduction measures were rapidly introduced and seemed to be successful in averting outbreaks for many years. In 2011, two major HIV outbreaks were reported among PWID in Athens, Greece, and Bucharest, Romania.Since then, more epidemics have occurred in Europe, North America, and the Middle East: in Tel Aviv, Israel (2012); Luxembourg (2013); Dublin, Ireland (2014); Indiana, USA (2014); and Saskatchewan, Canada (2016).1

In The Lancet HIV, Andrew McAuley and colleagues2 report on the Glasgow 2015 outbreak. Their Article Highlights the value of bio-behavioural surveillance in low-threshold settings to monitor blood-borne viruses and risk behaviours over time and thus to recognise outbreaks and identify their aetiology. Using data from the 201118 Needle Exchange Surveillance Initiative (NESI) surveys, a series of national crosssectional bio-behavioural surveys of PWID attending

services providing injecting equipment, the authors assessed the individual and environmental risk factors for HIV infection. In their final model, McAuley and colleagues found that HIV infection was most strongly associated with recent history of having injected cocaine (adjusted odds ratio 6.7, 95% CI 3.8 12.1) or experienced homelessness (3.0, 1.7 5.0). The authors attribute the outbreak in Glasgow to increases in homelessness; sharing of injecting equipment, as reflected by the high hepatitis C prevalence among HIV-infected cases; suboptimal awareness of HIV risk; and increases in cocaine injecting.

The increasing trend in cocaine use is not a local phenomenon. In recent years there has been a surge in the availability of high-purity cocaine in the European drug market, resulting in cocaine being the stimulant of choice for many drug users.The increase in cocaine injecting seems to have also had a role in the HIV outbreak among PWID in Luxembourg.

 The role of homelessness in HIV transmission has been identified in the Glasgow outbreak, as well as

in Dublin5 and Athens.Why are homeless PWID at higher risk of HIV, even after adjustment for high risk behaviours? It has been suggested that PWID who are homeless are more likely to be in the core of large, connected components in injection networks.This core has the potential to act as a centre of HIV transmission in case one or more of its members become infected.

McAuley and colleagues2 identified a non-significant increased risk among female PWID (adjusted odds ratio 1·7, 95% CI 0·93·2; p=0·083), which suggests that sexual transmission could have contributed to HIV infection among women. Sexual transmission among female PWID is corroborated by the association that was found between the number of sexual partners and HIV risk among women, but not among men, in the Athens outbreak.8 Despite the weak evidence in McAuley and colleagues results, this finding is worth noting as women were particularly affected in the HIV outbreaks in Dublin and Luxembourg.

An intriguing question is why a HIV outbreak occurred for the first time in 30 years in the context of a comprehensive harm reduction environment in Glasgow. Even in a setting with high-coverage needle and syringe programmes, there will inevitably be PWID with inadequate syringe acquisition; 1533% of participants in the 201116 surveys reported less than 100% syringe coverage in the past 6 months.This proportion is probably underestimated because it is derived from a sample of PWID attending injecting provision equipment services. Still, assuming that the coverage of harm reduction services was stable over time, the question remains: what triggered transmission? Homelessness, a frequently identified risk factor, increased in Scotland after 2000 and remained at high levels until 201011. Pylogenetic analysis of HIV sequences from the Glasgow outbreak reveals that the effective reproductive number (ie, the average number of secondary HIV infections originating from each individual) increased around the same period and peaked in 2009.Increases in homelessness might have resulted in changes in network cohesion (ie, in the connectedness within injection networks). Even if risk behaviours over time remain stable, changes in network cohesion might explain increased transmission.11 Thus, the introduction of HIV into a highly interconnected network of homeless people, along with the sharing of injecting equipment, might have triggered the outbreak. Additionally, the increased use of cocaine might have resulted in higher levels of HIV risk-taking behaviours and amplified transmission.

The size of the Glasgow outbreak was relatively small compared with those in Athens and Bucharest.1However, another intriguing question is why HIV transmission persisted for more than 3 years in Glasgow despite a multidisciplinary response that included linkage to HIV treatment of infected PWID, HIV education of those at risk, increased testing, and improved provision of injecting equipment.2 This approach might have not been successful in reaching those most in need quickly enough. The fact that the epidemic was recognised 6 years after the peak of secondary transmissionsuggests that there might be a subgroup of PWID not accessing services where they could be diagnosed and linked to treatment. Community-based approaches with peer-driven chain referrals, such as the ARISTOTLE programme in the Athens outbreakwhere this strategy was used to seek, test, and treat PWID, can help to increase the penetration into injection networks and to quickly reach those most at risk for HIV.

The Glasgow outbreak, along with other recent epidemics among PWID, underlines how vulnerable this population is to changes in the economic, social, and drugmarket scene and how fragile the success of interventions can be in preventing HIV outbreaks. High-coverage harm reduction programmes should be combined with surveillance of HIV infection and associated behaviours through community-based programmes, with an effort to reach the most underserved populations and to react rapidly to potential threats.

Vana Sypsa Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece