普遍檢測和治療 (UTT) 對病毒抑制和抗反轉錄病毒治療 (ART) 順從性的影響
資料來源:www.thelancet.com/hiv 2022 年 11 月 9 日 / 財團法人台灣紅絲帶基金會編
鑑於早期治療對健康和預防有益的有力證據,世衛組織於 2015 年修訂了其愛滋病毒治療指南,並建議不論 CD4 細胞計數或疾病階段如何,所有愛滋病毒感染者開始抗反轉錄病毒治療 (ART)。這一建議產生了巨大的影響,在資源有限的環境中改變 HIV計畫以及在非洲擴大 ART 計畫。然而,文獻中最初的擔憂和混合證據顯示,早期治療,尤其是對無症狀的 HIV 感染者,可能會導致較低的順從率和隨後的病毒抑制和較差的留存率。
普遍檢測和治療 (UTT) 包括在社區範圍內為所有 HIV 感染者提供帶有 ART 的 HIV 檢測服務。在 The Lancet HIV 中,David Macleod 及其同事在 UTT 社區隨機試驗中評估了 HIV 感染者的 ART順從性和病毒抑制。 HPTN 071 (PopART) 試驗於 2013 年至 2018 年在南非和尚比亞的 21 個社區進行。社區要麼是接受了 UTT 和其他連結照護、順從性和存留等的支持性介入,要麼就是根據國家指南提供對照社區標準的照護和ART。這項研究分析了人口發生率世代的橫斷面數據;只有那些知道並向採訪者透露了自己的愛滋病毒感染狀況,且目前正在接受抗反轉錄病毒治療的愛滋病病毒感染者才被納入分析。在世代中確定的 6,259 名 HIV 陽性者中,3,570 名 (57%) 符合納入標準。
對 UTT 介入實施 3 年後之 2016 年 5 月至 2017 年 5 月期間所獲得的橫斷面數據的分析發現,沒有證據顯示大規模介入的引入與較低的病毒抑制率或自我報告的順從率相關。這些發現具有重要的計畫意義,因為 UTT 和早期治療提供了識別、連結和治療HIV 感染者的機會,以實現病毒抑制的目標,特別是對於那些在高流行地區並不知悉自己的感染狀況、且可能沒有症狀、且否則可能不會以其他方式尋求檢測或治療者。
總體而言,接受 ART 並披露其狀態的個體的病毒未抑制率為 11·7%(3,554 人中的 416 人),自我報告的未順從率為 9·7%(3,566 人中的 345 人)。作者報告說,在所有分析的亞組中,目前接受 ART 的參與者中至少有 10% 沒有受到病毒抑制,即使他們報告說他們堅持治療。此外,在基準線時觀察到約 10% 的病毒未抑制率,並在整個研究過程中保持不變。作者懷疑這可能是由於耐藥性和未順從性的結合。在年輕人、男性、從事有害飲酒和娛樂性用藥的個人以及報告遭受恥辱的人中,病毒未被抑制的比例最高。這些發現顯示,許多 HIV 感染者是順從性強且病毒受到抑制,幾乎不需要支持性介入;然而,一些順從差和病毒不受抑制等風險較高的亞群體,可能會受益於或需要更有針對性和更深入的介入措施,以解決影響他們繼續接受治療的能力之問題和障礙。這一發現已在其他研究中得到證實,並且可以解釋為什麼在控制年齡和性別時,儘管在UTT組中已對連結、須從性和存留進行了額外的支持性介入,但研究的介入組和對照組之間的順從性或病毒抑制率並沒有差異。
隨著我們從 Macleod 及其同事和其他人的研究中,更多地了解影響最需要支持和介入的特定人群的問題後,我們將需要策略性地瞄準低計畫資源來解決這些特定人群的順從性問題。此外,在 PopART 和其他 UTT 研究的介入組中介入措施的實施(即與治療的連結以及對患者的追踪)可能會顯示對新開始 ART 的無症狀 HIV 陽性人群的順從性比那些已經接受照護和治療者的順從性上有更大的好處,因為新出現的證據顯示在開始 ART 的最初幾個月中存留率不佳的比例更高。在整個研究過程中觀察到的至少 10% 的病毒未抑制率,一致強化了定期病毒載量監測的重要性,尤其是在 U=U(無法檢測到=不會造成傳播)消息傳遞時代。
儘管 PopART 和其他 UTT 研究在識別和啟動 HIV 感染者治療方面取得了成功,但 Macleod 及其同事揭示了非洲環境中 ART 計畫面臨的持續挑戰。例如,在這項研究中,只有知道並披露了自己的愛滋病毒感染狀況並且目前正在接受抗反轉錄病毒治療的個人才被納入分析。因此,樣本中 88·8%(3,570 人中的 3,171 人)接受抗反轉錄病毒治療的愛滋病毒感染者是女性,這突出顯示在南非、尚比亞和其他國家,男性在了解自己的愛滋病毒狀況和接受治療方面仍然存在巨大差距。此外,在所有知道並披露其狀況的 HIV 感染者中,目前只有 82·1%(4,346 人中的 3,570 人)正在接受 ART。由於樣本中的潛在偏差以及更順從的 HIV 感染者的過多代表,在解釋這些數據時可能需要謹慎。
我們聲明沒有競爭利益。
*Pamela Bachanas, Janet Moore dtt6@cdc.gov
美國喬佐治亞州亞特蘭大,美國疾病控制和預防中心,全球愛滋病毒/愛滋病和結核病司
Effect of UTT on viral suppression and ART adherence
www.thelancet.com/hiv Vol 9 November 2022
With strong evidence of the health and prevention benefits of early treatment, WHO revised its HIV treatment guidelines in 2015 and recommended that all people living with HIV start antiretroviral therapy (ART) irrespective of CD4 cell count or disease stage.1 This recommendation resulted in dramatic changes to HIV programmes in resource-limited settings and the scale-up of ART programmes in Africa. However, there was initial concern and mixed evidence in the literature that early treatment, especially for people living with HIV who are asymptomatic, could lead to lower rates of adherence and subsequent viral suppression and poor retention.
Universal testing and treatment (UTT) includes the community-wide offer of HIV testing services with ART for all people living with HIV. In The Lancet HIV, David Macleod and colleagues evaluated ART adherence and viral suppression among people living with HIV in a community-randomised trial of UTT. The HPTN 071 (PopART) trial took place in 21 communities in South Africa and Zambia from 2013 to 2018. Communities either received UTT and other supportive interventions for linkage to care, adherence, and retention, or were control communities with standard of care and ART provided according to national guidelines. This study analysed cross-sectional data from a population incidence cohort; only people living with HIV who knew and disclosed their HIV status to the interviewer and were currently on ART were included in the analyses. Of 6259 HIV-positive people identified in the cohort, 3570 (57%) met the inclusion criteria.
Analysis of the cross-sectional data obtained between May, 2016, and May, 2017, following 3 years of delivery of the UTT intervention found no evidence that introduction of the large-scale intervention was associated with lower rates of viral suppression or self-reported ART adherence. These findings have important programme implications as UTT and early treatment offer opportunities to identify, link, and treat people living with HIV with the goal of achieving viral suppression, especially in people who are not aware of their status and are likely to be asymptomatic and might not otherwise seek testing or treatment in high prevalence areas.
Overall, the viral non-suppression rate among individuals on ART who disclosed their status was 11·7% (416 of 3554), and the self-reported nonadherence rate was 9·7% (345 of 3566). The authors reported that in all subgroups analysed, at least 10% of participants currently on ART were not virally suppressed, even when they reported being adherent to treatment. Further, viral non-suppression rates of about 10% were observed at baseline and remained throughout the study. The authors suspect that this could be due to a combination of drug resistance and non-adherence. Proportions of viral non-suppression were highest among young people, men, individuals who engaged in harmful drinking and recreational drug use, and those who reported experiencing stigma. These findings suggest that many people living with HIV are adherent and virally suppressed and could require little supportive intervention; however, some sub-groups at higher risk for non-adherence and non-suppression could benefit from or need more targeted and intensive interventions addressing the issues and barriers that interfere with their ability to remain on treatment. This finding has been shown in other studies5 and could explain why there were no differences in adherence or viral suppression rates between intervention and control arms of the study when controlling for age and gender, despite the additional supportive interventions for linkage, adherence, and retention in the UTT arms.
As we learn more about the issues that affect specific populations most in need of support and interventions from studies like this one by Macleod and colleagues and others, we will need to strategically target low programme resources to address the problems of adherence in these particular groups. In addition, interventions implemented in the intervention arms of PopART and other UTT studies (ie, linkage to treatment, and tracking and tracing of patients) could show greater benefits on adherence rates among asymptomatic HIV-positive people newly initiating ART than on adherence for those already enrolled in care and on treatment, as emerging evidence is revealing higher proportions of poor retention in the early months on ART initiation. The consistent rates of at least 10% viral non-suppression observed throughout the study reinforce the importance of regular viral load monitoring, especially in the era of U=U (undetectable=untransmissible) messaging.
Despite the success of PopART and other UTT studies for identifying and initiating people living with HIV on treatment, Macleod and colleagues4 revealed ongoing challenges for ART programmes in African settings. For example, in this study, only individuals who knew and disclosed their HIV status and were currently on ART were included in analyses. Consequently, 88·8% (3171 of 3570) of people living with HIV on ART in the sample were women, highlighting the continued large gap that remains in men learning their HIV status and getting on treatment in South Africa, Zambia, and other countries.10 In addition, of all the people living with HIV who knew and disclosed their status, only 82·1% (3570 of 4346) were currently on ART. Caution in interpreting these data might be warranted due to potential bias in the sample and over-representation of people living with HIV who are more adherent.
We declare no competing interests. *Pamela Bachanas, Janet Moore dtt6@cdc.gov Division of Global HIV/AIDS and TB, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA (PB, JM)