www.thelancet.com/hiv Vol 11 August 2024

富馬酸替諾福韋二吡呋酯 (Tenofovir disoproxil fumarate)與恩曲他濱 (emtricitabine) 聯合用作暴露前預防 (PrEP)，已被證明對於高感染風險個體（例如男男性行為者和血清相異伴侶）預防 HIV 非常有效。功效與劑量之次數直接相關，從每週2 天服用時的 76% 增加到每天服用時的 99%。正如所描繪的，PrEP 計畫的成功取決於依從性，這需要一個有效的監測系統來及時識別依從性不佳的個體。

主觀的依從性測量，例如自我報告和藥丸計數，具有廉價且易於實施的優點。然而，它們在準確性和可靠性方面存在很大的限制。由於這些限制，PrEP 的依從性已透過在各種生物基質（例如血漿、頭髮和乾血斑）中使用藥理學藥物濃度測定（替諾福韋或富馬酸替諾福韋二吡呋酯）來評估。在大多數藥理學測定中，治療藥物監測是透過使用液相層析串聯質譜法進行的，由於其無與倫比的準確性和精密度而被認為是黃金標準技術。然而，儘管液相層析串聯質譜法具有卓越的分析性能，但其成本高昂——不僅是測定本身，還因為設備昂貴、需要專業專業人員以及獲得結果所需的時間。這些因素對其在健康服務中的廣泛使用構成了障礙，特別是在低收入和中等收入國家擴大 PrEP 計畫時。因此，迫切需要更具成本效益的替代測定法，以促進更廣泛的取得和實施。

正是在這樣的背景下，莫妮卡 · 甘地及其同事在本期《刺胳針》愛滋病毒雜誌上報導的這項研究。作者使用了一種低成本的一站式照護點的免疫測定法，類似於用於 COVID-19 的測試，根據尿液中富馬酸替諾福韋二吡呋酯的濃度來檢測短期依從性。陽性結果顯示參與者在過去 4 天內服用了一劑藥物。考慮到測試可在 3 分鐘內提供結果，作者的目的是衡量醫療保健專業人員根據測試結果提供的即時回饋對提高參與者用藥依從性的影響。

為了實現這一目標，他們進行了一項隨機研究，涉及兩組沒有血清差異伴侶的肯亞婦女，該群體在撒哈拉以南非洲地區感染愛滋病毒的風險較高。這些女性在 PrEP 開始後進行每 3 個月的例行回診，在為期 12 個月的追蹤期中並每季進行一次訪視。所有參與者均接受 PrEP 治療，並在每次訪視時接受尿液檢測。然而，只有一組收到了基於測試結果的回饋，而另一組則收到了標準的遵守支持，因為醫療保健提供者不知道測試結果。

透過比較兩組女性中依從性的比例來評估測試知情回饋的效果。由於測試回饋的效果可能不僅限於短期依從性，Gandhi 和同事使用僅在最後一次追蹤時收集的頭髮富馬酸替諾福韋二吡呋酯濃度信息，根據女性的長期堅持情況對女性進行分類。如果在頭髮中檢測到富馬酸替諾福韋二吡呋酯，該女性被認為是具依從性的，然後比較兩組的長期依從性。

研究結果顯示，與接受標準照護組的女性相比，在四分之三的訪問中，接受測試告知回饋組的女性依從性比例顯著更高。介入前，尿液檢測諮詢組中可檢測到替諾福韋的比例為 65%，標準治療組為 71% (p=0·68)。 12 個月時，介入組43 人中有31 人(72%) 尿液中可檢測到替諾福韋，而標準照護組42 人中有19 人(45%) 尿液中可檢測到替諾福韋(p=0·0015)。此外，接受測試回饋的女性長期堅持的勝算比幾乎是接受標準護理的女性的三倍。儘管仍處於起步階段，但這些發現是有希望的，因為它們顯示尿液即時檢測結果對於制定向參與者提供即時回饋的策略上是有價值的信息，旨在提高那些持續在感染愛滋病毒高風險狀況的人之依從性。

鑑於基於即時測試結果的諮詢的相關作用，一些考慮因素很重要。儘管諮詢的目標族群是不遵從者，但有些策略也應該針對依從者，因為藥物陽性結果並不能提供有關其遵守程度的足夠詳細資訊。對於不依從的女性，重要的是要確定增加她們脆弱易感性的結構和社會因素。此外，有必要了解其對風險的認知，因為具有較高風險行為的人的依從性往往較高。

撒哈拉以南非洲地區的愛滋病毒預防必然涉及提供 PrEP 並制定策略以提高順性別婦女的依從性。正如作者指出的那樣，這項研究的進展可能會提供新的資訊來改善介入措施，從而增強這些婦女的權能，在減少伴侶干擾的情況下將愛滋病毒感染的風險降至最低。

作者聲明沒有競爭利益。

*Iuri da Costa Leite、丹尼爾·薩維尼翁·馬里尼奧 iuri.fiocruz@gmail.com

Escola Nacional de Saúde Pública Sergio Arouca，巴西里約熱內盧（IdCL、DSM）

Low-cost point-of-care urine test to enhance PrEP adherence

www.thelancet.com/hiv Vol 11 August 2024

    Tenofovir disoproxil fumarate combined with emtricitabine, used as pre-exposure prophylaxis (PrEP), has proven to be highly effective in preventing HIV among individuals at high risk of infection, such as men who have sex with men and serodifferent couples. Efficacy is directly related with the number of doses, increasing from 76% when taken 2 days per week to 99% when taken daily. As depicted, the success of a PrEP programme depends on adherence, which requires an efficient monitoring system to promptly identify individuals with suboptimal adherence.

    Subjective measures of adherence, such as self-report and pill count, have the advantages of being inexpensive and easy to implement. However, they have substantial limitations in terms of accuracy and reliability. Owing to these limitations, PrEP adherence has been assessed by use of pharmacological drug concentration assays (tenofovir or tenofovir disoproxil fumarate) in various biomatrices such as plasma, hair, and dried blood spot. In most pharmacological assays, therapeutic drug monitoring is carried out by use of liquid chromatography–tandem mass spectrometry, consi dered the gold-standard technique owing to its unmatched accuracy and precision. However, despite its superior analytical performance, liquid chromatography tandem mass spectrometry comes with substantial costs—not only for the assays themselves but also because of the expensive equipment, the need for specialised professionals, and the time required to obtain results. These factors pose barriers to its widespread use in health services, particularly in expanding PrEP programmes in low-income and middle-income countries. Consequently, there is a pressing need for more cost-effective alternative assays to facilitate broader access and implementation.

    It is within this context that the study reported in this issue of The Lancet HIV by Monica Gandhi and colleagues is set. The authors used a low-cost point-of-care immunoassay, similar to the test used for COVID-19, to detect short-term adherence on the basis of the concentration of tenofovir disoproxil fumarate in urine. A positive outcome indicated that a participant had taken a dose of the medication within the past 4 days. Considering the test provides results within 3 min, the authors aimed to measure the effect that immediate feedback from health-care professionals, based on the test results, can have on improving medication adherence among participants.

    To accomplish this objective, they carried out a randomised study with two arms involving Kenyan women without serodifferent partners, the group at higher risk of HIV exposure in sub-Saharan Africa. The women were enrolled at their 3-month routine visit after PrEP initiation and were followed quarterly for 12 months. All participants received PrEP and underwent urine testing at each visit. However, only one group received feedback based on the test results, whereas the other group received standard adherence support, as the health-care providers were unaware of the test results.

    The effect of test-informed feedback was assessed by comparing the proportion of adherent women in the two groups. As the effect of the test-informed feedback might not be restricted to short-term adherence, Gandhi and colleagues8 used information on hair tenofovir disoproxil fumarate concentration, collected only at the final follow-up visit, to classify women on the basis of their long-term adherence. Women were considered adherent if tenofovir disoproxil fumarate was detected in their hair. The two groups were then compared in terms of their long-term adherence.

    The study results indicate that the proportion of adherent women in the test-informed feedback group was significantly higher in three out of four visits, compared with those receiving standard care. Pre intervention, urine tenofovir was detectable in 65% in the urine-test counselling group and 71% in the standard of-care group (p=0·68). At 12 months, 31 (72%) of 43 in the intervention group had detectable urine tenofovir compared with 19 (45%) of 42 in the standard-of-care group (p=0·0015). Moreover, the odds of women with test-informed feedback having long-term adherence were almost three times higher than those of women with standard care. Although still incipient, these f indings are promising as they show that the urine point of-care test result is valuable information for developing strategies to provide real-time feedback to participants, aiming to increase adherence among those at ongoing high risk of HIV infection.

    Given the relevant role of counselling based on real time test results, some considerations are important. Although the target population for counselling is patients who are non-adherent, some strategies should be directed towards patients who are adherent as well, since a positive result does not provide detailed information on the degree of adherence. For non-adherent women, it is important to identify the structural and social factors that increase their vulnerability. Additionally, it is necessary to understand the perception of risk, as adherence tends to be higher among those with higher risk behaviours.

    HIV prevention in sub-Saharan Africa necessarily involves the availability of PrEP and the development of strategies to increase its adherence among cisgender women. Developments from this study, as the authors point out, might provide new information to improve interventions, resulting in greater empowerment of these women to minimise the risks of HIV infection with less interference from their partners.

The authors declare no competing interests.

*Iuri da Costa Leite, Daniel Savignon Marinho iuri.fiocruz@gmail.com

Escola Nacional de Saúde Pública Sergio Arouca, Rio de Janeiro, Brazil (IdCL, DSM)