「真實世界」研究發現，PrEP 可能會阻止 60% 的法國愛滋病高危男性感染愛滋病毒

資料來源：格斯.凱恩斯 / 2022 年 6 月 29 日/ aidsmap / 財團法人台灣紅絲帶基金會編譯

 

圖片來源：邁克爾.莫洛尼/Shutterstock.com

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在法國進行的一項研究將服用 PrEP 的成年男性的新 HIV 診斷與未服用的具有相似風險的男性的診斷相匹配，發現 PrEP 在阻止這一高危人群感染方面的總體有效性為 60 %。

這個 60% 的有效性數據包括一些在研究期間停止 PrEP 至少三個月並且在許多情況下沒有恢復的男性。未停用 PrEP 的男性的 PrEP 有效性為 86%，與隨機對照試驗中的結果相似。

來自法國國家藥品和健康產品安全局 (ANSM) 的 Hugo Jourdain 及其同事也發現，PrEP 在 30 歲以下男性中的有效性僅為 26%，而在 40 歲以上男性中為 83%，並且在收入非常低的男性中成效為零甚至有負面影響，儘管該等人中只有少數的愛滋病毒病例。但這種低效率可能是由於在這些群體中難以堅持使用 PrEP。

該研究涵蓋了透過法國公共衛生系統免費提供 PrEP 的前五年。在法國推廣採用每日和基於事件的 PrEP方家。

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研究設計

這項研究是全國性的：它使用了一個匿名且具有代表性的數據庫，該數據庫包含所有使用法國衛生系統的人。

在類似的全國或全州研究以比較 PrEP 使用者和非使用者之間的 HIV 感染率，例如來自澳大利亞新南威爾士州或蘇格蘭的一項研究，均存在一項問題以顯示PrEP 使用者和非使用者確實有著相似罹患 HIV 的風險，因而所呈現的感染減少是由 PrEP 導致。

為了解決這個問題，研究人員抽取了 256 名在 2016 年 1 月至 2020 年 6 月的研究期間成為 HIV 陽性的男性（「病例」樣本，並將他們與同期保持 HIV 陰性的一組男性進行匹配，但他們被認為係具有同樣高的愛滋病毒風險（「控制」）。該對照組包含相同數量的服用和未服用 PrEP 的男性。

如果組中感染 HIV 的 PrEP 使用者較少，研究人員就可以計算 PrEP 預防的感染比例。

儘管如此，由於數據庫記錄了處方、診斷和程序，研究人員缺乏個人行為數據。因此，他們使用的「高風險」標準是基於匿名記錄中可用的：測試。

要成為保持 HIV 陰性的男性的匹配對照組，受試者必須在研究期間的兩年內進行至少四次 HIV 篩查測試和一次 STI 測試，之後至少再進行一次 HIV 測試。研究人員計算出，這種測試頻率與所有參與者可能感染愛滋病毒的「背景風險」相關，並且也與 PrEP 使用者的最低測試制度相似。

數據如下：在研究期間，總共有 28,352 名 18-65 歲的男性開始了 PrEP 並且至少有一次重複處方。在同一時間段內，研究人員發現了 18,354 名「高風險」非 PrEP 用戶，他們的 HIV 和 STI 檢測頻率如上所述。

在這組 46,706 名男性（包括 PrEP 使用者和非使用者）中，有 260 人在研究期間被診斷出感染了 HIV。

256 例病例均與 3 至 5 名對照者相匹配，每名對照者均處於同樣高風險且也具有其他相似特徵，即年齡、地理、他們所在地區的愛滋病毒流行率、以及他們是否參加了針對低收入人群的法國健康援助計劃。對照組在 591 名 PrEP 用戶和 622 名非用戶之間幾乎均分，但病例和對照組與 PrEP 的使用不匹配——僅與它們的其他特徵匹配。

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結果

在研究期間感染 HIV 的 256 人中，有 73 人 (29%) 使用了 PrEP——亦即 71% 的人沒有使用。這意味著 PrEP 使用者最終感染 HIV 的可能性僅為非使用者的 40%——換句話說，它的有效率為 60%。

在確實感染 HIV 的 PrEP 使用者中，大多數（78%）在研究期間使用 PrEP 的時間不到一半，只有 7%（五名男性）的使用時間超過 75%。相比之下，在未感染 HIV 的使用 PrEP 的對照組中，使用 PrEP 的時間不到一半者為40%，使用超過四分之三的時間者同樣是 40%。

「該研究無法區分不經常但正確按需要使用PrEP者和採每日使用 PrEP者但其依從性不足之間的區別」。

在 HIV 檢測呈陽性的 PrEP 使用者中，88%（73 名感染 HIV 的 PrEP 使用者中的 64 人）在研究期間的某個時間點停止了 PrEP。然而，其中 34 人重新啟動了它，其中 47% 感染了 HIV。

如果服用 PrEP 的人在第一次停藥後被排除在研究之外，那麼只有 10 人在第一次連續（儘管不一定完全依從）PrEP 期間感染了 HIV。這相當於 PrEP 的有效率為 86%，只要人們沒有停藥期。

如上所述，PrEP 對 30 歲以下男性的有效率僅為 26%（35% 的 HIV 病例是 PrEP 使用者，幾乎與未感染 HIV 的 42% 的 PrEP 使用者一樣高）。它對 30 多歲的男性有效率為 66%，對 40 歲及以上的男性有效率為 83%。

它對生活在大城市（人口超過 200,000）的人有 65% 的效果，但對生活在小社區（人口低於 10,000）的人只有 28% 的效果。它對居住在法國低流行地區的人的有效率僅為 24%，而在巴黎地區為 67%，在其他高流行地區為 70%。

實際上，在收入足夠低（定義為法國貧困水平的 50%）的 PrEP 使用者中，有更高比例的新 HIV 病例為有資格獲得免費的國家資助的醫療保健者，而並非大多數以保險為基礎的醫療保健者當中感染到。使用 PrEP 的 38 名男性中有 9 例（24%），而未使用 PrEP 的 61 名男性中有 11 例（18%），但數字太低而無統計學意義。然而，它確實顯示低收入人群——如年輕人和農村地區的人——可能難以繼續進行 PrEP。

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結論

本研究旨在包括具有相似 HIV 風險的 PrEP 使用者和非使用者群體，以排除可能高估或低估 PrEP 真正功效的風險差異。

研究人員確實承認他們在識別「高風險」控制方面存在局限性，這些控制是通過頻繁進行 HIV 和 STI 檢測來定義的。這意味著他們可能會錯過一部分愛滋病毒高風險但不經常或根本不進行檢測的男性。由於進行測試是服用 PrEP 的一部分，「隱形」的高風險非測試者群體往往會增加未服用 PrEP 的 HIV 感染者的比例。這往往會增加其明顯的有效性。

在評論中，來自巴伐利亞健康和食品安全局的 Liza Coyer 博士和阿姆斯特丹公共衛生服務局的 Elske Hoornenborg 博士也提請注意，在法國的男同性戀者中，256 例 HIV 病例僅佔每年診斷出的 1000 多例新病例的一小部分。因此可能不能代表所有新診斷出感染愛滋病毒的男性，尤其是感染愛滋病毒低風險的男性。

該研究的另一個限制是它對 PrEP 使用方法上的衡量——即處方補充——無法區分正確按需要但不經常使用PrEP者和按每日使用 PrEP但依從性不足者之差別。然而，以前的研究，包括關鍵的法國研究 IPERGAY，似乎顯示正確按需要使用PrEP 與每日 PrEP 一樣有效——包括在 Elske Hoornenborg 是合著者的這項「現實世界」研究中。

正如他們評論的那樣，最引人注目的發現是年輕男性中 PrEP 的低效率，這一發現在許多不同的研究中得到了重複。 Coyer 和 Hoornenborg 敦促採取新的結構性和個性化介入措施，以提高年輕男性 PrEP 的可及性、依從性和持續性，包括更多的線上取得、將性健康服務整合納入當地社區倡議，以及獲得新的藥效更持久的 PrEP 配方。

參考文獻：

Jourdain H 等人。法國 HIV 感染高危男性暴露前預防在真實世界的有效性：一項巢式病例對照研究。 刺胳針公共衛生 7，e529-e536，2022 年 6 月。見 https://doi.org/10.1016/S2468-2667(22)00106-2。

Coyer L 和 Hoornenborg E. 。充分發揮 HIV 暴露前預防的預防潛力。刺胳針公共衛生 7，e488-e489。見 https://doi.org/10.1016/S2468-2667(22)00116-5。

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

‘Real-world’ study finds PrEP may be stopping 60% of HIV infections in French men at high risk of HIV

Gus Cairns / 29 June 2022 / aidsmap

 

Michael Moloney/Shutterstock.com

A study in France that matched new HIV diagnoses in adult men who had been taking PrEP with diagnoses in men at similar risk who had not been taking it, has found that the overall effectiveness of PrEP in stopping infection in this high-risk population was 60%.

This 60% effectiveness figure included some men who discontinued PrEP for at least three months during the study period and who in many cases did not resume it. PrEP effectiveness in men who did not discontinue PrEP was 86%, similar to that found in randomised controlled trials.

Hugo Jourdain and colleagues, from the French National Agency for the Safety of Medicines and Health Products (ANSM), also found that PrEP only had 26% effectiveness in men under 30, compared with 83% in men over 40, and had zero or even negative effectiveness in men on very low incomes, though there were only a few HIV cases in this group. This low effectiveness may be due to difficulties in sticking with PrEP in these groups.

The study covers the first five years of PrEP being freely available through France’s public health system. Both daily and event-based PrEP are promoted in France.

The study design

This study was nationwide: it used an anonymised and representative database of all people using the French health system. 

Similar nation- or state-wide studies that compare the HIV infection rate among PrEP users and non-users, such as a study from New South Wales in Australia or one from Scotland, have the problem of showing that PrEP users and non-users really are at similar risk of HIV and therefore that it was PrEP that lead to the reduction in infections seen.

To solve this problem, the researchers took a sample of 256 men who became HIV-positive during the study period of January 2016 to June 2020 (‘cases’) and matched them with a group of men who remained HIV-negative during the same period, but who they deemed to have similarly high risk of HIV (‘controls’). This control group contained equal numbers of men who took PrEP and did not take it. 

If there were fewer PrEP users in the group that did acquire HIV, the researchers could then calculate the proportion of infections that were prevented by PrEP.

Nonetheless, because the database records prescriptions, diagnoses and procedures, the researchers lacked personal, behavioural data. The criteria for ‘high risk’ they used was therefore based on what is available in anonymised records: tests.

To be in the matched comparison group of men who stayed HIV negative, subjects had to have had at least four HIV screening tests and one STI test within two years during the study period, and at least one more HIV test thereafter. This frequency of tests, the researchers calculated, correlated with the likely ‘background risk’ of HIV in all participants, and was also similar to the minimum testing regime expected of PrEP users.

The figures are as follows: in total, 28,352 men aged 18-65 initiated PrEP and had at least one repeat prescription during the study period. Within the same timespan the researchers found 18,354 ‘high risk’ non-PrEP users with the frequency of HIV and STI tests described above.

In this group of 46,706 men, both PrEP users and non-users, there were 260 who were diagnosed with HIV in the study period. 

The two hundred and fifty-six cases were each matched with three to five controls each who were at similarly high risk and who also had other similar characteristics, namely age; geography; HIV prevalence in their area; and whether they were on the French health assistance programme for people on very low incomes. The controls were almost equally split between 591 PrEP users and 622 non-users, but the cases and controls were not matched by PrEP use – only by their other characteristics. 

Results

Seventy-three (29%) of the 256 people who acquired HIV during the study period had used PrEP – meaning that 71% had not. This means that PrEP users were only 40% as likely to end up acquiring HIV as non-users – in other words, it was 60% effective.

Of the PrEP users who did acquire HIV, most (78%) used PrEP less than half the time during the study period and only 7% (five men) used it more than 75% of the time. In contrast, among the PrEP-using controls who did not acquire HIV, equal numbers used PrEP less than half the time (40%) and more than three-quarters of the time (again, 40%).

“The study could not distinguish between infrequent but correct use of on-demand PrEP and inadequate adherence to daily PrEP.”

Of the PrEP users who tested HIV-positive, 88% (64 of the 73 PrEP users who acquired HIV) discontinued PrEP at some point during the study period. However 34 of them restarted it, and of these, 47% acquired HIV.

If people taking PrEP were excluded from the study after their first discontinuation, then there were only ten people who acquired HIV during their first continuous (though not necessarily fully adherent) period on PrEP. This equated to PrEP being 86% effective, as long as people did not have a period of discontinuation.

As mentioned above, PrEP was only 26% effective in men under 30 (35% of cases of HIV were PrEP users, almost as high a proportion as the 42% of PrEP users who did not catch HIV). It was 66% effective in men in their thirties and 83% effective in men aged 40 and above.

It was 65% effective in people living in large cities (population over 200,000), but only 28% effective in people living in small communities (population under 10,000). And it was only 24% effective in people living in low-prevalence areas of France, compared to 67% in the Paris region and 70% in other high-prevalence areas.

There was actually a higher proportion of new HIV cases in PrEP users who had a low-enough income (defined as 50% of the French poverty level) to be eligible for free state-financed healthcare, as opposed to the insurance-based healthcare most people get. There were nine cases among 38 men who used PrEP in this category (24%) versus 11 cases among 61 men who did not (18%), but the numbers were too low to be statistically significant. It does, however, indicate that people on low incomes – like young people and ones in rural areas – may have difficulty in PrEP continuation.

Conclusions

This study was constructed to include groups of PrEP users and non-users at similar risk of HIV, to rule out differences in risk that could over- or under-estimate the true efficacy of PrEP. 

The researchers do acknowledge limitations in their identification of ‘high-risk’ controls, who were defined by their taking frequent HIV and STI tests. This means they could be missing out a proportion of men who were at high risk of HIV but did not test often, or at all. Since having tests is a part of taking PrEP, a population of ‘invisible’ high risk non-testers would tend to increase the proportion of those acquiring HIV who did not take PrEP. This would tend to increase its apparent effectiveness.

In a commentary, Dr Liza Coyer from the Bavarian Health and Food Safety Authority and Dr Elske Hoornenborg of the Public Health Service of Amsterdam also draw attention to the fact that the 256 HIV cases represent a small proportion of the more than 1000 new cases diagnosed annually in gay men in France, so may possibly not have been representative of all men newly diagnosed with HIV, especially of lower-risk men who nonetheless acquired HIV.

The other limitation of the study was that its measure of PrEP use – which was prescription refills – could not distinguish between infrequent but correct use of on-demand PrEP and inadequate adherence to daily PrEP. However previous studies, including the pivotal French study IPERGAY, appear to show that on-demand PrEP used correctly is as effective as daily PrEP – including in this ‘real-world’ study of which Elske Hoornenborg was a co-author.

The most striking finding, as they comment, is the low effectiveness of PrEP among young men, a finding which has been duplicated in many different studies. Coyer and Hoornenborg urge new structural and personalised interventions to improve accessibility, adherence and continuation of PrEP among young men including more online access, sexual health services integrated into local community initiatives, and access to the new longer-lasting formulations of PrEP.

References

Jourdain H et al. Real-world effectiveness of pre-exposure prophylaxis in men at high risk of HIV infection in France: a nested case-control study. Lancet Public Health 7, e529-e536, June 2022. See https://doi.org/10.1016/S2468-2667(22)00106-2.

Coyer L and Hoornenborg E. Reaching the full preventive potential of HIV pre-exposure prophylaxis. Lancet Public Health 7, e488-e489. See https://doi.org/10.1016/S2468-2667(22)00116-5.