長效抗反轉錄病毒藥物：非洲的研究和實施考慮因素

資料來源：www.thelancet.com/hiv Vol 10 July 2023

    我們對 Jean B Nachega 及其同事最近對長效抗反轉錄病毒治療 (ART) 和順從性的審查表示讚賞。這個問題對於世衛組織非洲區域尤為重要，該區域承擔著全球愛滋病毒/愛滋病負擔的三分之二，並且有超過2,000萬人正在接受抗反轉錄病毒療法。迄今為止，波札納是唯一一個批准長效卡博特韋加利匹韋林 (cabotegravir plus rilpivirine) 的非洲國家，理由是潛在的順從性益處。然而，交付尚未開始，有待數據來指導實施。

長效卡博特韋聯合利匹韋林在這種情況下（包括兒童、青少年和妊娠期）的臨床試驗已計畫或已經在進行中。我們目前正在進行「用長效抗反轉錄病毒藥物改善非洲愛滋病毒結果」(IMPALA) 試驗，研究每月2 次使用卡博特韋加利匹韋林對有病毒學控制不佳史的成年人的有效性。正如模型研究所示，這一人群尤其可以受益於更有利於順從性的長效 ART，同時並將出現耐藥性的額外風險降至最低。

長效卡博特韋聯合利匹韋林因其在減少恥辱和藥物負擔方面的潛在益處而受到很高的需求，鑑於持續的流行病，迫切需要提供長效產品。然而，還有一些重要的實施挑戰需要解決，包括儘管獲得耐藥性檢測的機會有限，但仍要仔細針對病毒學失敗風險低的個體、HIV病毒載量監測頻率、冷鏈要求以及排除B型肝炎合併感染。附錄中列出的研究將提供線上查看附錄通信關鍵數據，以告知愛滋病毒治療模式典範轉移的最大影響，這對於實現聯合國愛滋病規劃署到2030年終止愛滋病流行的目標至關重要。

FVC 已獲得楊森 (Janssen)、ViiV 和吉利德 (Gilead) 的資助，並且是 ViiV 資助的實施試驗的指導委員會成員。 LAO 已獲得 ViiV 和吉利德 (Gilead) 的贈款資金、邁蘭 (Mylan) 的差旅支持，並且是葛蘭素史克 (GSK) 領導的科學顧問委員會的成員。 所有其他作者均聲明不存在競爭利益。

*Claire Norcross、Loice Achieng Ombajo、Sheetal Kassim、Nigel Garrett、Fiona V Cresswell、Eugene Ruzagira claire.norcross@lshtm.ac.uk

英國倫敦衛生與熱帶醫學院臨床研究系（CN、FVC）； 內羅畢大學臨床醫學和治療學系，肯亞內羅畢（LAO）； 內羅畢大學流行病學建模和分析中心，肯亞內羅畢（LAO）； 德斯蒙德·圖圖健康基金會，南非開普敦（SK）； 開普敦大學德斯蒙德·圖圖愛滋病毒中心，南非開普敦（SK）； 南非愛滋病研究計畫中心 (CAPRISA)，誇祖魯–納塔爾大學，南非德班 (NG)； 南非德班誇祖魯納塔爾大學護理與公共衛生學院公共衛生醫學系（NG）； 英國布萊頓布萊頓和蘇塞克斯醫學院全球健康與感染系 (FVC)； 醫學研究委員會/烏干達病毒研究所和倫敦衛生與熱帶醫學學院烏干達研究中心，烏干達恩德培（ER、FVC）； 英國倫敦衛生與熱帶醫學院傳染病流行病學系（ER）

Long-acting antiretrovirals: research and implementation considerations in Africa

www.thelancet.com/hiv Vol 10 July 2023

    We applaud Jean B Nachega and colleagues on their recent review of long-acting antiretroviral therapy (ART) and adherence. This issue is particularly important for the WHO African region, which bears two-thirds of the global HIV/AIDS burden and has more than 20 million people on ART. To date, Botswana is the only African nation that has approved long-acting cabotegravir plus rilpivirine, citing potential adherence benefits. However, delivery has not yet commenced, pending data to guide implementation.

Clinical trials of long-acting cabotegravir plus rilpivirine in this setting, including in children, adolescents, and pregnancy, are planned or already underway (appendix). We are currently conducting the Improving HIV outcomes in Africa with Long-acting Antiretrovirals (IMPALA) trial, investigating the effectiveness of 2-monthly cabotegravir plus rilpivirine among adults with a history of suboptimal virological control. This population could particularly benefit from more adherence-friendly lon-acting ART with the least additional risk of emergent resistance, as shown in modelling studies.

Long-acting cabotegravir plus rilpivirine is in high demand for its potential benefits in reducing stigma and pill burden, and there is an urgent need to make longacting products accessible given the ongoing epidemic. However, there are important implementation challenges to address, including careful targeting of individuals at low risk of virological failure despite limited access to drug resistance testing, HIV viral load monitoring frequency, coldchain requirements, and exclusion of hepatitis B co-infection. The studies listed in the appendix will provide See Online for appendix Correspondence critical data to inform a maximum impact of this paradigm shift in HIV treatment, essential to reaching the UNAIDS target of ending the AIDS epidemic by 2030.

FVC has received grant funding from Janssen, ViiV, and Gilead and is on the steering committee of a ViiV-funded implementation trial. LAO has received grant funding from ViiV and Gilead, travel support from Mylan, and is on a GSK-led scientific advisory board. All other authors declare no competing interests.

*Claire Norcross, Loice Achieng Ombajo, Sheetal Kassim, Nigel Garrett, Fiona V Cresswell, Eugene Ruzagira claire.norcross@lshtm.ac.uk

Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK (CN, FVC); Department of Clinical Medicine and Therapeutics, University of Nairobi, Nairobi, Kenya (LAO); Center for Epidemiological Modelling and Analysis, University of Nairobi, Nairobi, Kenya (LAO); Desmond Tutu Health Foundation, Cape Town, South Africa (SK); Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa (SK); Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu–Natal, Durban, South Africa (NG); Department of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa (NG); Global Health & Infection Department, Brighton & Sussex Medical School, Brighton, UK (FVC); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda (ER, FVC); Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK (ER)