直接觀察治療可以成為照顧HIV治療失敗患者的有用工具
Michael Carter / 2019年8月13日/ aidsmap news/ 財團法人台灣紅絲帶基金會編譯
美國一項新的研究表明，一些愛滋病毒陽性患者具有抗反轉錄病毒治療（ART）的豐富經驗，抗藥性和極少之治療選擇顯示需要強化順從性之支持，以便將其病毒載量抑製到不可檢測的水平。
該研究表明，順從性不佳很大比例是重度先前治療患者中病毒持續複製的可能原因，並且有治療順從性問題的人，往往生活在高度社會排斥中。該研究發表在「臨床傳染病」線上版中，收治了20名重度重覆經歷ART治療的患者，並具有可檢測的病毒載量和耐藥性。他們接受了住院治療，並在施用ART時採直接觀察治療法（DOT）進行。
雖然大多數服用現代抗反轉錄病毒療法的人都有很好的療效，但有少數人在接受抗反轉錄病毒治療後，仍持續維持病毒量，可能的原因包括缺乏ART效力，預先存在的耐藥性和對治療的順從性不佳。
當缺乏順從性是ART失敗的原因時，必須確定原因並制定未來的支持策略。否則，患者可能會循環於不同治療方案中並進一步發展出耐藥性。
由美國國立衛生研究院的Nicole Winchester所領導的一個研究小組發現，一些重度重覆接受過ART治療且具有可檢測到之病毒載量的住院患者，在按照護理人員指示每天服用抗反轉錄病毒治療後病毒載量大幅下降。因此，他們假設順從性不佳是許多重度重覆ART治療患者中其病毒學失敗的根本原因。
為了驗證這一理論，他們設計了一項涵括20名儘管至少採用了兩種先前的ART方案，仍然病毒學失敗之確診個案的研究（最近兩次病毒載量測量超過1000拷貝/ ml），而所有人都使用目前的抗愛滋病毒藥物組合至少六個月。
從患者的病歷中獲得治療史和先前的耐藥性測試結果。
在給予知情同意後，參與者被送進診所進行為期8天的研究。參與者被要求繼續服用他們現有的抗反轉錄病毒療法，並在家中模仿進行他們的抗反轉錄病毒治療方案。若在規定的給藥時間的兩小時內沒有服用，則要求由護理人對治療的個體進行治療。這種情況亦記錄在患者的病歷中。
病毒載量和抗逆轉錄病毒藥物濃度水準持續監測。並向患者提供有關愛滋病毒、順從性諮詢的教育，並提供心理評估和支持。在研究結束時，參與者返回到門診治療。
研究參與者的中位年齡為46歲，60％為男性，85％為黑人，25％在出生時獲得愛滋病毒。大多數患有晚期HIV疾病，其中90％的CD4計數低於200個細胞/立方毫米，且在此世代中的中位數細胞數為54個細胞/立方毫米。研究開始時的中位病毒載量約為40,000拷貝/毫升。在治療史上，參與者平均服用了12種抗反轉錄病毒藥物，有21種主要的耐藥性突變，並且平均接受抗反轉錄病毒治療17年。四分之一的患者之前曾接受過單劑或雙劑治療不佳的ART治療。
有45％的參與者對直接觀察治療( DOT ) 產生反應（病毒載量下降至少0.5 log10）。這證實了不順從是病毒學失敗的原因。
對DOT有反應的參與者其病毒載量平均下降1.52 log10，而沒有反應的參與者則下降0.10 log10。
在研究期間，三分之一具有病毒學反應之參與者和45％沒有反應的參與者中，至少有一次沒有按時地要求治療之情況。
對直接觀察治療( DOT ) 的反應，參與者之間存在顯著差異。與沒有反應的個體相比，有反應的參與者服用較少的抗HIV藥物（平均9對14，p = 0.004），他們也有較少的主要抗藥性突變（6對24，p = 0.001），且其身上病毒對ART更敏感（p <0.001）。
調查人員發現了在遵循醫囑上的重大社會經濟障礙。對DOT做出回應的人其教育水平較低，在就業、住房、糧食不安全和心理健康狀況上需要更多的社會工作者之支持。「提供住院的設置為跨學科團隊提供了更多時間來識別和解決關鍵的順從性障礙」，作者評論道。
在研究結束後，三分之二對DOT做出反應的參與者有至少六個月的門診治療追蹤。其中有5名參與者至少有一次病毒載量測量低於40拷貝/毫升，但長期只有一名患者保持病毒抑制；然而，所有六名參與者的CD4細胞計數均顯著增加。對DOT沒有反應的8名參與者有活躍的ART選擇上的變換，並返回第二次DOT住院停留以便開始新的治療方案；其中有三個人出現了新的耐藥性。
「我們發現，短期DOT可以成為有效的工具，去確認順從性不佳是導致病毒學失敗的主要原因，並防止不必要的處方改變並指導隨後的追蹤」，研究者總結道。他們認為針對門診患者採用較不密集的策略，例如使用智能手機虛擬DOT的方式，也可能具有價值。
Directly observed therapy can be a useful tool in caring for people with HIV treatment failure
Michael Carter/ 13 August 2019
Some HIV-positive patients with extensive experience of antiretroviral therapy (ART), drug resistance and few treatment options need intensive adherence support in order to suppress viral load to undetectable levels, according to new US research.
The study demonstrated that suboptimal adherence was the likely cause of ongoing viral replication in a significant proportion of heavily pre-treated patients, and that people with adherence issues were often living with high levels of social exclusion. Published in the online edition of Clinical Infectious Diseases, the research involved 20 heavily ART-experienced patients with detectable viral load and drug resistance. They were admitted to inpatient care where ART was administered using directly observed therapy (DOT).
Although most people taking modern ART have excellent outcomes, a minority of people on ART have a persistent viral load. Possible reasons include lack of ART potency, pre-existing resistance and suboptimal adherence to therapy.
When lack of adherence is the reason for ART failure, it is essential to identify the causes and to develop strategies for support in the future. Otherwise, there is a risk that patients will cycle through treatment options and develop further drug resistance.
A team of investigators led by of the US National Institutes of Health noticed that several heavily ART-experienced patients with a detectable viral load who were admitted to hospital had substantial falls in viral load following daily dosing of ART by nursing staff. They therefore hypothesised that suboptimal adherence was the underlying reason for the virological failure of ART in many heavily treated patients.
To test this theory, they designed a study involving 20 people with confirmed virologic failure (two recent viral load measurements above 1000 copies/ml), despite taking at least two previous ART regimens. All had been taking their current combination of anti-HIV drugs for at least six months.
Treatment history and results of previous resistance tests were obtained from the patients’ notes.
After giving informed consent, the participants were admitted to a clinic for an eight-day study. The participants were asked to continue taking their existing ART and to mimic their ART adherence regimen at home. Individuals who did not ask for their therapy within two hours of their stated dosing time had the therapy administered by nursing staff. Such instances were recorded in the patients’ notes.
Viral load and antiretroviral drug levels were monitored. The patients were provided with education about HIV, adherence counselling and received psychological assessments and support. At the end of the study, the participants returned to outpatient care.
Study participants’ median age was 46, 60% were male, 85% were black and 25% acquired HIV at birth. Most had advanced HIV disease, with 90% having a CD4 count below 200 cells/mm3 and a median cell count in the cohort of 54 cells/mm3. Median viral load at the start of the study was approximately 40,000 copies/ml. In terms of treatment history, participants had taken an average of twelve previous antiretroviral drugs, had 21 major resistance mutations and had been on ART for an average of 17 years. A quarter of patients had previously taken suboptimal ART with single or dual therapy.
A response to DOT (a fall in viral load of at least 0.5 log10) was seen in 45% of participants. This confirmed non-adherence as the cause of virologic failure.
Viral load fell by an average of 1.52 log10 in participants with a response to DOT compared to a fall of 0.10 log10 in participants who did not have a response.
During the study, a third of participants with a virological response and 45% of those without a response did not request their therapy on time on at least one occasion.
There were significant differences between participants according to DOT response. Participants with a response had taken fewer previous anti-HIV drugs compared to individuals without a response (average 9 vs 14, p = 0.004), they also had fewer major drug resistance mutations (6 vs 24, p = 0.001) and had virus that was more susceptible to ART (p < 0.001).
The investigators identified significant socio-economic barriers to adherence. People who responded to DOT had lower education levels and required more frequent social worker support with employment, housing, food insecurity and mental health conditions. “The inpatient setting provided the multidisciplinary team more time to identify and address key adherence barriers,” comment the authors.