在法國第一年的PrEP研究結果顯示按需要時給藥與每日給藥一樣

 

在法國第一年的PrEP研究結果顯示按需要時給藥與每日給藥一樣有效

在法國參加暴露前預防(PrEP)示範研究的1,628人中沒有新的愛滋病毒感染。巴黎狄德羅大學的Jean-Michel Molina在阿姆斯特丹第22屆國際愛滋大會上的新聞發布會上說,超過一半的參與者選擇按需要時服用PrEP,其餘的選擇每日服用,但兩者都同樣有效。

Prévenir”(預防)研究正在收集有關在巴黎及其郊區提供PrEP的最佳方式的數據。研究人員希望去顯示在額外3,000人服用PrEP後將導致該地區男男性接觸者的HIV診斷明顯下降。

Molina在三年研究的第一年(從20175月開始)提供了數據。研究共招募了1,628人,其中幾乎所有人(98.8%)都是男男性接觸者,只有十二名異性戀男女以及八名變性者加入。大多數參與者都是三十歲或四十出頭 ; 約有一半以上的人沒有經常之性伴侶 ; 57%的人之前曾在Prévenir註冊之前使用過PrEP

參與者可以選擇是否遵循在IPERGAY研究中驗證的按需要給藥時間表(有時稱為「事件驅動」或「基於事件方式」給藥),或者使用每日劑量,這種方式更常用於世界其他地方。按需給藥包括在預期性行為前2-24小時服用雙倍劑量的PrEP(兩片),然後,如果發生性行為,則在雙倍劑量後24小時和48小時內服用另外的藥丸。如果連續幾天發生性行為,應該每天服用一粒藥丸,持續直到最後一次性行為後48小時。在參加計畫時,選擇按需要給藥的比例為54.6%,選擇每日者為45.4%。根據需要選擇的數量遠遠高於比利時和荷蘭的研究,詳如底下所述。

選擇這兩種方式給藥的人的概況存在一些差異。那些選擇每日劑量的人往往有較多的性伴侶(過去3個月中有15個)和更多的無套性行為(過去4周中有3次),相對於選擇按需要給藥者(分別為102)。儘管該試驗已開放一年,但平均追蹤時間為7個月。 Molina分別在按需要和每日組中提供了506443人年的追蹤數據。結果兩組均無新感染。因此,按需要組的年發病率為095%信賴區間為0-0.7),每日組亦為095%信賴區間為0-0.8)。研究人員估計,到目前為止,在這一1,628人的世代中,已經避免了85例愛滋病毒感染。

根據自我報告,接受按需要使用PrEP的人的報告,96.2%的性行為已經被PrEP所「覆蓋」 - 這意味著該等人在性行為之前和之後服用了推薦的劑量。每日服用PrEP的人則相當於95.8%。在使用按需要和每日PrEP的人中,有22%和19%的人在性行為中使用避孕套。

有跡象顯示性行為發生了變化,在研究的第一年,雖然平均伴侶人數下降,但在過去四周中無套性行為則呈現增加,按需耍使用PrEP者其中位數為24 ; 而在每日PrEP用戶中則為三到六次。然而,由於只有不到十分之一的人,其參與研究之時間足以提供全年的數據,因此應謹慎解釋這些結果。

已經有11例A型肝炎、C型肝炎或E型肝炎感染(發病率在雙邊均僅略高於1%)。副作用和腎臟異常結果受到限制,兩組之間沒有差異。研究存留率良好(每年中輟率為3.3%)。

Molina認為這些數據強化了按需要採用PrEP方式的安全性和有效性(目前由歐洲愛滋病臨床協會以及法國、英國、加拿大和澳大利亞的國家機構指導支持)。他在新聞發布會上說,這是一個有可能提高PrEP接愛率的選擇。

在比利時和荷蘭按需要給藥之執行情形

比利時還有一項示範研究,提供按需要或每日PrEP,稱為Be-PrEP-ared。研究人員招募了197名男同性戀者和3名變性女性。與法國相比,超過四分之三的人選擇每日劑量,而四分之一的人選擇按需要服用。儘管數量很少,但按需要組的依從性似乎較差(約佔PrEP所涵蓋性行為的70%)。

儘管自我報告的風險行為水平很高,性傳播感染率亦很高,但在追蹤的前12個月內沒有人感染愛滋病毒。這些是中期結果,研究仍在繼續。

阿姆斯特丹PrEP項目(AmPrEP)的設置與此類似。 20158月至20183月期間,共有370名男同性戀者和兩名變性人參與,其中73%選擇每日PrEP27%選擇按需要服藥。正如之前報導的那樣,一個每天服用PrEP的人卻獲得HIV感染的情況實在是非常不尋常。

隨著荷蘭研究的有更長的追蹤時間,研究人員能夠提供有關人們在給藥方案間轉換之更有意義的數據。在服用PrEP的前兩年,49%開始按需要服用的人和20%開始每日服藥的人至少換過一次(有些人來回轉換)。年輕人更容易轉換 ; 有很多性行為的人更有可能從按需要服用藥物方式中轉離。

研究人員表示,大量的轉換顯示了PrEP用戶需求上的變化,研究者也因此建議在提供PrEP服務時應重視執行方法中以客戶為中心此種價值。

 

On-demand dosing as effective as daily dosing in first year of French PrEP study

 

Roger Pebody

Published: 24 July 2018

There have been no new HIV infections in the 1628 people taking part in a demonstration study of pre-exposure prophylaxis (PrEP) in France. Over half of participants chose to use on-demand dosing for PrEP, with the rest opting for daily dosing, but both have been equally effective, Jean-Michel Molina of the University of Paris Diderot told a press conference at the 22nd International AIDS Conference (AIDS 2018) in Amsterdam today.

The ‘Prévenir’ (prevent) study is gathering data on the best ways to deliver PrEP in Île-de-France, which is the region of Paris and its suburbs. The researchers hope to show that having an extra 3000 people take PrEP will result in a marked fall in HIV diagnoses among men who have sex with men in the region.

Molina presented data on the first year (from May 2017) of the three-year study. A total of 1628 people have enrolled, almost all of whom (98.8%) are men who have sex with men. Twelve heterosexual men and women as well as eight transgender people have enrolled.

Most participants are in their thirties or early forties; just over half do not have any regular sex partners; and 57% had previously used PrEP before enrolling in Prévenir.

Participants can choose whether to follow the on-demand dosing schedule (sometimes referred to as ‘event-driven’ or ‘event-based’ dosing) that was validated in the IPERGAY study, or to use daily dosing, which is more commonly used in other parts of the world. On-demand dosing involves taking a double dose of PrEP (two pills) from 2-24 hours before anticipated sex, and then, if sex happens, additional pills 24 hours and 48 hours after the double dose. In the event of sex on several days in a row, one pill should be taken each day until 48 hours after the last sexual intercourse.

At enrolment, on-demand dosing was chosen by 54.6% and daily by 45.4%. The number choosing on-demand is much higher than in the Belgian and Dutch studies, reported below.

There were some differences in the profiles of those choosing the two options. Those choosing daily dosing tended to have had more sexual partners (15 in the past three months) and more condomless sex (three times in the past four weeks) than those choosing on-demand dosing (ten and two, respectively).

Although the trial has been open for a year, the average (mean) period of follow-up is seven months. Molina presented data on 506 and 443 person-years of follow-up in the on-demand and daily groups, respectively.

There have been zero infections in both groups. Annual incidence in the on-demand group is therefore 0 (95% confidence interval 0-0.7) and in the daily group 0 (95% confidence interval 0-0.8). The researchers estimate that, so far, 85 HIV infections have been avoided in this cohort of 1628 people.

Based on self report, 96.2% of sexual acts reported by people taking on-demand PrEP have been ‘covered’ by PrEP – meaning that the person took the recommended doses before and after sex. The equivalent figure for those taking daily PrEP is 95.8%.

Condoms have been used during 22% and 19% of sexual acts, in those using on-demand and daily PrEP, respectively.

There are indications of changes in sexual behaviour. Over the first year of the study, while average partner numbers have declined, condomless sex has increased – in on-demand PrEP users, from a median of two to four times in the past four weeks; in daily PrEP users, from three to six times. However, as less than one in ten people have been in the study long enough to provide data over the full year, these results should be interpreted with caution.

There have been eleven infections of hepatitis A, C or E (an incidence of just over 1% in both arms). Side-effects and abnormal kidney results have been limited, with no differences between arms. Study retention has been good (a drop-out rate of 3.3% per year).

Molina believes these data strengthen the case for the safety and effectiveness of on-demand PrEP (currently supported by guidelines of the European AIDS Clinical Society as well as the national bodies in France, the UK, Canada and Australia). It is an option that has the potential to boost the uptake of PrEP, he told the press conference.

On-demand dosing in Belgium and the Netherlands

Belgium also has a demonstration study offering either on-demand or daily PrEP, known as Be-PrEP-ared. The researchers have recruited 197 gay men and three transgender women. In contrast to France, over three-quarters selected daily dosing, whereas a quarter chose on-demand. Although the numbers are small, adherence appears to be poorer in the on-demand group (around 70% of sexual acts covered by PrEP).

Despite high levels of self-reported risk behaviour and a high incidence of sexually transmitted infections, there have been no HIV infections in the first 12 months of follow-up. These are interim results and the study continues.

The set-up of the Amsterdam PrEP Project (AmPrEP) is similar. Between August 2015 and March 2018, 370 gay men and two transgender people have enrolled, with 73% choosing daily PrEP and 27% on-demand. As previously reported, there has been a highly unusual case of a man taking daily PrEP acquiring HIV.

With the Dutch study’s longer period of follow-up, the researchers are able to give more meaningful data on people switching between dosing regimens. In the first two years of taking PrEP, 49% of those who began with on-demand dosing and 20% of those who began with daily dosing have switched at least once (some people have switched back and forth). Younger people were more likely to switch; people having a lot of sex were more likely to switch away from on-demand dosing.

The researchers say that the high number of switches show how PrEP users’ needs vary and suggest the value of a client-centered approach in providing PrEP.

References

Molina JM et al. Incidence of HIV-infection in the ANRS Prevenir Study in the Paris Region with daily or on demand PrEP with TDF/FTC. 22nd International AIDS Conference (AIDS 2018), Amsterdam, abstract WEAE0406LB, 2018.

Vuylsteke B et al. Daily or event-driven PrEP? Interim results of “Be-PrEP-ared”, a PrEP demonstration project among men who have sex with men in Belgium. 22nd International AIDS Conference (AIDS 2018), Amsterdam, abstract THPEC320, 2018.

 

Hoornenborg E et al. Different PrEP modalities for different people: switches between daily and event-driven PrEP among MSM and TGP. 22nd International AIDS Conference (AIDS 2018), Amsterdam, abstract LBPEC034, 2018.