PrEP使用者的性傳染病感染增加主要集中在少數男性中,部分原

PrEP使用者的性傳染病感染增加主要集中在少數男性中,部分原因是因性病篩檢之擴增

在澳大利亞維多利亞省伯內特研究所的Michael Traeger,在阿姆斯特丹舉行的第22屆國際愛滋病大會報告了這些數據。該省中首次接受暴露前預防(PrEP)的男同性戀和雙性戀男性其細菌引起之性傳染病感染(STIs)顯著增加,但感染主要集中在PrEP使用者中的一部分--13%的男性,其中有53%的人先前即有性病之診斷。此外,一旦該研究的統計學家考慮到同時也提升了性病之測試48%這一點,這就減弱了性病總體發病率的增加。

會議還聽取了一個美國研究世代的數據,該世代描繪了同性戀和雙性戀男性在服用PrEP之前、期間和之後的性行為。在PrEP使用期間,人際間的分析顯示出在男性有更多的無套性行為,在停止使用PrEP期間則顯著下降。整體對性傳染病之感染的影響較小。

澳大利亞

澳大利亞於2014年對PrEP進行了首次試點研究,於2016年初獲得監管部門的批准,並於20183月開始提供其大部分費用。墨爾本(維多利亞省首府)的採用速度很快 -20151月使用PrEP者占同性戀者的6%,到20181月上升至18%。

許多服用PrEP的人都是PrEPX計畫的參與者,這是一項針對某一地區不同地點的10家診所的實施研究。該研究的主要目的是觀察PrEP的使用是否與全省愛滋病毒感染減少有關,但在本次會議中其期中調查結果亦呈現了該研究的次要結果 - 性傳染病之感染。

數據來自該研究的4,275名參與者中的2,981名參與者,這些參與者是在與強化數據監控之ACCESS計畫合作的部分診所中加入的。幾乎所有人(98%)都是同性戀和雙性戀男性,他們的中位年齡為34歲,48%的人在加入前的三個月內曾有接受性的無套肛交,28%的人之前使用過PrEP

在一年多一點的追蹤期間,52%沒有感染性病。性傳染病感染高度集中在少數重複感染的PrEP使用者中--25%的參與者有兩次或更多次的感染,佔感染者的76%;13%的參與者有三次或更多次感染,佔感染的53%。

所有參與者平均感染性傳染病感染的總發病率為每100人年91.9。這意味著在一組100人中追蹤一年,將有大約92個性病診斷。這並不意味著100名男性中的92人會患有性傳播途徑 - 其中一些男性在一年中會有多次的性病感染。

最常見的感染是披衣菌和淋病。直腸感染的發病率為每100人年56.6 ; 尿道感染每100人年22.​​4 ; 和咽部感染每100人年23.5

接下來的分析研究了在參加PrEPX之前就曾就診過同一診所的1,378名參與者。這使得研究人員能夠將加入前12個月的性病發病率與PrEPX進行中的性病發病率進行比較。

在加入PrEPX之前服用PrEP的男性中,加入研究前的發病率為每100人年92.4,而在PrEPX執行中為每100人年104.1。這種差異並未達統計學上意義。

然而,首次服用PrEP的男性其性病發病率大大增加 - 從每100人年55.1增加到每100人年94.2(增加71%,p = <0.001)。在查看關於該問題的任何數據時需要考慮的一個重要因素是,PrEP用戶需要每三個月測試一次性病感染,從而增加診斷感染性病的機會。首次服用PrEP的人的檢測率提高了48%,這引入了所謂「檢測偏差」。在對此進行統計調整後,性病發病率增加了21%。這仍然具有統計學意義(p = 0.006),但具有中等臨床意義。

與性病感染相關的主要行為因素是有更多的性伴侶和更頻繁的群體性行為。使用保險套或多或少經常對於性病率生率沒有任何影響。這顯示要減少PrEP使用者重複性的感染性病的介入措施,應該要更多地關注於性伴侶數量和群體的性行為,而不是保險套的使用。

美國

亨特學院的Jonathon Rendina提供了來自One Thousand Strong研究世代的男同性戀和雙性戀男性的數據。該世代並非設立用於追踪PrEP使用情況,但恰好緊接在PrEP2014年獲得批准後不久即招募參與者,並且從那時起繼續讓PrEP參與者參與年度調查。因此,該世代提供了在美國PrEP推出的最初幾年中行為改變的見解:3%的參與者在2014 - 15年參加研究時服用PrEP,在一年後完成調查後升至8%(2015- 16),14%完成兩年調查(2016-17),21%完成三年調查(2017-18)。這是一個主要是白人和相對富裕的世代。與其他一些研究世代相比,招募對象並不是針對愛滋病風險特別高的個人。

1,071名參與者中,有313人報告至少在一次調查中使用了PrEP。雖然之前的一些研究剛剛在使用PrEP之前和開始使用PrEP幾個月後對性行為進行了比較,但此等數據的一個優點是它包括一些人在開始PrEP後一年或兩年所收集的數據。在使用PrEP的最初幾週或幾個月內,有些人可能會有一種特別的自由感和大量的無套性行為,但這種行為不一定會持續下去。此外,上一次調查中有5%的受訪者之前曾使用過PrEP但已經停止使用 - 該研究亦提供了對停止PrEP後性行為的深入了解。

根據是否在使用PrEP前(2.79)、使用PrEP中(7.13)或停止PrEP後(2.09)的一段時間中,無套性行為的數量是非常不同的。並沒有太多男性報告曾與愛滋病毒陽性伴侶進行接受式無套性接觸,且這些數據顯示與前一研究具有相同的趨勢 - 使用PrEP前(0.19)、使用PrEP中(0.94)和停止PrEP之後(0.12)。這些差異在統計學上都很重要。

PrEP似乎正適切地在為使用它的人服務」Jonathon Rendina評論道。 「當他們處於高風險時,他們正在接受PrEP,並且當他們不再處於高風險時,他們正在停止PrEP」。

作為研究的一部分,參與者在調查的同時採取了直腸拭子以便治療披衣菌和淋病。在使用PrEP之前,7%的男性患有性病 ; 使用PrEP時有10%得到感染 ; 停止PrEP後,只有2%的人感染。

鑑於PrEPHIV感染的影響,Rendina質疑性病升高的重要性。他問:「繼續我們關於風險代償的辯論是否值得,如果這意味著從7%的發病率上升到10%的發病率呢?」

 

Increase in STIs in PrEP users is concentrated in a minority of men and is partly due to more STI screening

Roger Pebody

Published: 01 August 2018

There were significant increases in bacterial sexually transmitted infections (STIs) in gay and bisexual men taking pre-exposure prophylaxis (PrEP) for the first time in Victoria, Australia, but infections were concentrated in a subset of PrEP users – 13% of the men had 53% of the STI diagnoses. Moreover, there was a 48% increase in STI testing which attenuated the overall increase in STI incidence, once it had been taken into account by the study’s statisticians.

Michael Traeger of the Burnet Institute reported these data at the 22nd International AIDS Conference (AIDS 2018) in Amsterdam last week.

The conference also heard data from an American cohort which charted gay and bisexual men’s sexual behaviour before, during and after taking PrEP. Within-person analyses showed much more condomless sex during periods of PrEP use, which significantly decreased in periods when men had discontinued PrEP. There was less of an impact on STIs.

Australia

Australia had its first pilot studies of PrEP in 2014, gave regulatory approval in early 2016 and began to reimburse most of its cost in March 2018. Uptake has been rapid in Melbourne (the capital of the state of Victoria) – 6% of gay men were using PrEP in January 2015, rising to 18% in January 2018.

Many of those taking PrEP are participants in PrEPX, an implementation study at ten clinics in a range of locations. The study’s primary objective is to see if the use of PrEP is associated with a reduction in HIV infections across the state, but the conference presentation gave interim findings on the study’s secondary outcome – sexually transmitted infections.

Data come from 2981 of the study’s 4275 participants, those who enrolled at a clinic that contributes enhanced surveillance data as part of the ACCESS collaboration. Almost all (98%) are gay and bisexual men, their median age is 34 years, 48% had had condomless receptive anal sex in the three months before enrolling and 28% had used PrEP before.

During follow-up of a little more than a year, 52% had no STIs. STIs were highly concentrated in a minority of PrEP users who had repeat infections – 25% of participants had two or more infections, accounting for 76% of infections. Thirteen per cent of participants had three or more infections, accounting for 53% of infections.

The overall incidence of STIs, averaged out across all participants, was 91.9 per 100 person-years. This means that in a group of 100 people followed for one year, there would be around 92 STI diagnoses. It does not mean that 92 of the 100 men would have an STI – a few men would have multiple STIs during the course of the year.

The most common infections were chlamydia and gonorrhoea. Incidence of rectal infections was 56.6 per 100 person-years; urethral infections 22.4 per 100 person-years; and pharyngeal infections 23.5 per 100 person-years.

The next analysis looked at 1378 participants who had been attending the same clinic before they enrolled in PrEPX. This allowed the researchers to compare STI incidence in the 12 months before enrolment with STI incidence while in PrEPX.

Among men who had taken PrEP before joining PrEPX, incidence was 92.4 per 100 person-years before joining the study and 104.1 per 100 person-years while in PrEPX. This difference was not statistically significant.

However, incidence was greatly increased for men who took PrEP for the first time – from 55.1 per 100 person-years to 94.2 per 100 person-years (a 71% increase, p = < 0.001). An important factor that needs to be taken into account when looking at any data on this issue is that PrEP users are required to test for STIs every three months, thus multiplying the opportunities for infections to be diagnosed. The testing rate increased by 48% in people taking PrEP for the first time, which introduces a ‘detection bias’.

After making statistical adjustment for this, STI incidence increased by 21%. This remained statistically significant (p = 0.006) but is of moderate clinical significance.

The main behavioural factors which were associated with STIs were having more sexual partners and having group sex more frequently. Using condoms more or less often did not make any difference to STI rates. This suggests that interventions to reduce repeat STIs in PrEP users should focus more on partner numbers and on group sex than on condom use.

United States

Jonathon Rendina of Hunter College presented data from the One Thousand Strong cohort of gay and bisexual men. The cohort was not set up to track PrEP usage but happened to enrol participants shortly after PrEP was approved in 2014 and has continued to engage its participants with annual surveys since then. The cohort therefore provides insight into changing behaviour during the first years of PrEP rollout in the US: 3% of participants were taking PrEP when they enrolled in the study in 2014-15, rising to 8% completing a survey after one year (2015-16), 14% completing the two-year survey (2016-17) and 21% of those in the three-year survey (2017-18).

This is a predominantly white and relatively affluent cohort. In contrast to some other cohorts, recruitment was not focused on individuals at particularly elevated risk of HIV.

Of the 1071 participants, 313 reported using PrEP during at least one survey. Whereas some previous studies have just had comparisons of sexual behaviour immediately before using PrEP and a few months after starting it, one strength of this data set is that it includes some data collected a full year or two after people started PrEP. During the first few weeks or months of using PrEP, some people may have a particular feeling of freedom and a great deal of condomless sex, but that behaviour won’t necessarily be sustained. Also, 5% of respondents in the last survey had previously used PrEP but had discontinued – the study provides insight into sexual behaviour after stopping PrEP.

The number of condomless sex acts was very different according to whether it was a period of time before using PrEP (2.79), while using PrEP (7.13) or after stopping PrEP (2.09). Not many men reported condomless receptive sex with HIV-positive partners, but these data showed the same pattern – before using PrEP (0.19), while using PrEP (0.94) and after stopping PrEP (0.12). These differences were all statistically significant.

“PrEP appears to be serving its exact purpose for the men who use it,” commented Jonathon Rendina. “They are taking PrEP when they are engaging in high risk and they are stopping PrEP at times when they are no longer at high risk.”

As part of the study, participants took a rectal swab for chlamydia and gonorrhoea at the same time as the survey. Before using PrEP, 7% of men had STIs; while using PrEP, 10% did; and after stopping PrEP, only 2% did.

Rendina questioned the importance of such rises in STIs given PrEP’s impact on HIV infection. He asked: “Is it worthwhile to continue our debates about risk compensation if what this means may be a jump from 7% incidence to 10% incidence?”

References

Traeger M et al. Changes, patterns and predictors of sexually transmitted infections in gay and bisexual men using PrEP; interim analysis from the PrEPX demonstration study. 22nd International AIDS Conference (AIDS 2018), Amsterdam, abstract THAC0502, 2018.

Rendina HJ et al. Changes in rectal STI incidence and behavioral HIV risk before, during, and after PrEP in a national sample of gay and bisexual men in the United States. 22nd International AIDS Conference (AIDS 2018), Amsterdam, abstract TUAC0202, 2018.