進展上的不完善：阿片類藥物依賴的治療選擇
資料來源：剌胳針愛滋病毒www.thelancet.com/hiv Vol 8 February 2021，財團法人台灣紅絲帶基金會編譯
聯合國的會員國已制定了以下目標，將於2030年結束愛滋病毒大流行：到2025年，95％愛滋病毒感染者應了解自己的感染狀況，其中的95％感染者應接受抗反轉錄病毒治療（ART），接受ART者中應有95％將實現病毒被抑制。藥癮者可以且應該從抗反轉錄病毒療法中受益，抗反轉錄病毒療法將改善其健康狀況並保護其性伴侶避免遭受到愛滋病毒的傳播。
世衛組織針對靜脈注射藥癮者的公共衛生應對定義為涵括多項的健康介入措施（清潔針具設施的取得，美沙酮維持的替代治療或丁丙諾啡用於阿片類藥物依賴的人，以及獲得愛滋病毒檢測和治療的機會），並解決其於獲取這些服務上的結構性障礙。人們擔心，沒有接受阿片類藥物依賴治療的阿片類藥癮者可能無法成功維持其抗病毒藥物治療方案和達到病毒被抑制。一些國家仍將活躍於注射毒品的人排除在抗反轉錄病毒療法治療範圍之外（於136個報告國家中有3個）。阿片類激動劑療法可以幫助阿片類藥物依賴且係HIV之感染者維持其抗病毒治療方案，並達到病毒被抑制。
P Todd Korthuis及其同事在《剌胳針愛滋病毒》期刊中報告了越南一項隨機、開放性、非劣效性試驗的結果，該試驗比較了以愛滋病毒診所為基礎的丁丙諾啡加納洛酮與轉介接受美沙酮維持治療的阿片依賴的愛滋病毒感染者之比較。他們的假設（丁丙諾啡加納洛酮在病毒抑製作用上不會有較差程度的表現，可增加了阿片類藥物依賴治療上的選擇）於他們所得到的數據上並未獲得支持。他們發現丁丙諾啡加納洛酮的療效明顯不及轉介美沙酮維持治療的療效。丁丙諾啡價格昂貴，尤其是與納洛酮合用時，但潛在地可提供了藥癮者減少門診次數。受限於越南國家政策，這項研究並未採用帶回家的劑量，這明顯上是丁丙諾啡方案的優勢之一；越南於2020年12月4日批准了多日美沙酮試點計劃（第5074 QD-BYT號決定）。
美沙酮和丁丙諾啡名列於世界衛生組織的基本藥物中，但對丁丙諾啡與納洛酮的聯合用藥則沒有明確的建議。社區偏好和個人選擇對於阿片類激動劑治療計劃的成功至關重要。阿片類激動劑療法往往是長期的治療，有時是終身治療。計劃應以人為本，重點是促進靈活的交付選擇和綜合服務，以減輕服務使用者和衛生系統每日觀察配藥上的負擔。兩種藥物的回家劑量至關重要。衛生服務的整合必須根據服務使用者的喜好仔細考量，並且必須提供有利的環境，能減少污名和歧視並有受歡迎之員工；還必須解決基於性別的障礙。根據美沙酮和丁丙諾啡的不同藥物配方，以及不同的生理耐受性和個人喜好，藥物使用者通常會對某一種藥物的耐受性更高。通常，習慣於較高劑量的阿片類藥物的人使用美沙酮可獲得更好的療效。阿片類藥癮者應在低閾值的基礎上獲得最適合他們劑量的藥物，其中並包括一旦服藥穩定後可提供帶回家的劑量。
獲得包括阿片類激動劑在內的管製藥物是健康權的既定且關鍵要素。為實現這一權利，人們採取了基於實證的藥物依賴療法的選擇應該是可用的、可近的、可接受的，並應具有高品質。且應擴大服務使用者的治療素養，以促進自我倡導並提高服藥順從性。
在Korthuis及其同事進行的研究中，拘留和監禁是接受研究參與者常見的障礙。拘留對丁丙諾啡加納洛酮於計畫中的存留產生負面影響，在這種情況下，等同於抗病毒治療ART的存留。聯合國在2012年呼籲關閉強制性藥癮拘留設施，並於2018年將藥物使用和擁有的行為除罪化。對藥物依賴採取懲罰性措施會對公共衛生產生負面影響，並有可能對全球愛滋病毒治療的系列目標減緩其進展。
Korthuis等認為，在HIV治療診所中，與HIV有關的恥辱感可能已成為阿片類藥物依賴治療的障礙。由越南愛滋病毒感染者的恥辱指數（2012年）研究發現，比起愛滋病毒感染者，將自己識別為注射毒品的人更具恥辱感。恐怕單僅係因愛滋病毒的恥辱感似乎並非是丁丙諾啡加納洛酮組藥效結果欠佳的原因。越南值得稱許的是擴大了美沙酮維持療法方案並考慮使用丁丙諾啡。但是，在越南和全球範圍內，藥癮者仍然面臨到結構性，程序性和個人上的障礙。
透過最大程度地增加阿片類藥物依賴和愛滋病毒等之治療機會，提供服務使用者彈性的選擇，並且在沒有污名和歧視下，這將使我們更接近愛滋病毒的治療目標。
Imperfect progress: treatment options for opioid dependence
UN Member States have set the following targets to end the HIV pandemic by 2030: by 2025, 95% of people living with HIV will know their status, 95% of those will receive antiretroviral therapy (ART), and 95% of those receiving ART will achieve viral suppression. People who use drugs can, and should, benefit from ART, which will improve their health and wellbeing and protect their sexual partners from HIV transmission.
WHO defines a public health response for people who inject drugs as one that involves interventions for health (access to sterile injecting equipment, substitution therapy with maintenance methadone or
buprenorphine for people dependent on opioids, and access to HIV testing and treatment) and addresses structural barriers to accessing these services. There are concerns that people with opioid dependence who are not receiving treatment for opioid dependence might not successfully maintain their ART regimen and viral suppression. Some countries still exclude people who are actively injecting drugs from access to ART (17 of 136 reporting countries). Opioid agonist therapy can help people living with opioid dependence and HIV to maintain their ART regimen and, subsequently, viral suppression.
In The Lancet HIV, P Todd Korthuis and colleagues report the results of an open-label, randomised, noninferiority trial in Vietnam to compare HIV clinicbased buprenorphine plus naloxone with referral for methadone maintenance therapy for people with opioid dependence living with HIV. Their hypothesis— that buprenorphine plus naloxone would lead to noninferior levels of viral suppression, adding a treatment option for opioid dependence—was not supported by their data. They found that buprenorphine plus naloxone was significantly less efficacious than referral for methadone maintenance therapy. Buprenorphine is more expensive, especially combined with naloxone, but offers potentially reduced numbers of clinic visits for service users. Limited by national policy, this study did not apply take-home dosing, which is ostensibly one of the strengths of buprenorphine programmes; Vietnam approved a pilot of multi-day methadone on Dec 4, 2020 (decision 5074 QD-BYT).
Methadone and buprenorphine are listed as WHO essential medicines, but there is no explicit recommendation regarding combined buprenorphine plus naloxone. Community preferences and individual options are important to the success of opioid agonist therapy programmes. Opioid agonist therapy tends to be a long-term, occasionally life-long, treatment. Programmes should be people-centred, focusing on promotion of flexible delivery options and integrated services to reduce the burden of daily observed dispensing for service users and the health system. Take-home doses of both medications are essential. Integration with health services needs to be considered carefully, based on the preferences of service users, and must be accompanied by enabling environments, with reduced stigma and discrimination and welcoming staff. Gender-based barriers must also be addressed. People who use drugs usually tolerate one medication better than another, based on the different pharmaceutical formulations of methadone and buprenorphine, as well as divergent physiological tolerance and individual preferences. Typically, people accustomed to higher doses of opioids achieve better results with methadone. People who are opioid dependent should have access to the medication that suits them best on a low-threshold basis, which includes the provision of take-home doses, once stabilised.
Access to controlled medicines, including opioid agonist therapy, is an established and key element of the right to health. In fulfilment of this right, options for evidence-based therapy for drug dependence
should be available, accessible, acceptable, and of good quality. Treatment literacy among service users should be expanded to promote self-advocacy and improve adherence.
Detention and imprisonment were common barriers to treatment access among participants in the study by Korthuis and colleagues. Detention negatively affected retention on buprenorphine plus naloxone, which, in this case, is equivalent to retention on ART. The UN called for the closure of compulsory drug detention facilities in 2012 and for decriminalisation of drug use and possession in 2018. Punitive approaches towards drug dependence negatively affect public health, potentially slowing gains towards global HIV treatment targets.
Korthuis and colleagues suggested that HIV-related stigma might have been a barrier to treatment uptake for opioid dependence in HIV treatment clinics. The Vietnam People Living with HIV Stigma Index (2012) found that identifying as a person who injects drugs was more stigmatising than living with HIV. It seems unlikely that fear of HIV stigma alone was a causal factor in the suboptimal outcomes of the buprenorphine plus naloxone group. Vietnam can be commended for expanding methadone maintenance therapy programmes and considering buprenorphine. However, structural, programmatic, and individual barriers remain for people who use drugs, both in Vietnam and globally. Maximising treatment access for opioid dependence and HIV with flexible service-user options, and without stigma and discrimination, will bring us closer to HIV treatment targets.
*Keith M Sabin, Naomi Burke-Shyne, Judy Chang, Colleen Daniels, Van T T Nguyen, Annette Verster sabink@unaids.org
Strategic Information Department, UNAIDS, 20 Avenue Appia, 1211 Geneva 27, Switzerland (KMS); Harm Reduction International, London, UK (NB-S, CD); International Network of People who Use Drugs, London, UK (JC); HIV, Viral Hepatitis and STI Team, WHO, Hanoi, Vietnam (VTTN); Department of Global HIV, Hepatitis, and STI Programmes, WHO, Geneva, Switzerland (AV)