誰會有注射治療失敗的風險？
資料來源：Keith Alcorn / 2022 年 11 月 1 日 / aidsmap / 財團法人台灣紅絲帶基金會編譯
Chloe Orkin 教授在 2022 年格拉斯哥 HIV 大會上發表演講。圖片來自 Alan Donaldson Photography。
倫敦大學瑪麗女王大學的 Chloe Orkin 教授上週在 HIV 感染藥物治療國際大會 (HIV Glasgow) 上報告說，在開始聯合用藥之前存在的三個因素強烈預測使用可注射型 cabotegravir 和 rilpivirine 進行的抗反轉錄病毒治療的病毒學失敗。這些因素可用於識別 HIV 感染者是否有更高的風險經歷該治療方案的失敗。
儘管可注射的 cabotegravir/rilpivirine 方案失敗在臨床試驗中很少見，僅影響 1.4% 的參與者，但預測那個人不太可能從該方案中獲益，可以防止治療失敗和耐藥性的發展。這對於可注射的 cabotegravir/rilpivirine 而言尤為重要，因為這些長效製劑會在血液中保留很長時間，可能會加劇耐藥性的出現。
導致注射用 cabotegravir/rilpivirine 獲得許可的 III 期臨床試驗的研究人員對來自三項研究的試驗數據進行了分析，以確定整個研究期間病毒學失敗的風險因素。
在 HIV Glasgow 2022 上，Chloe Orkin 教授談到誰有注射治療失敗的風險。
該分析匯集了 ATLAS 研究（至第 96 週）、FLAIR 研究（至第 124 週）和 ATLAS-2M 研究（至第 152 週）的數據。分析了兩組因素：變量在開始治療前和治療期間測量（在 1,224 名具有完整研究數據的參與者中）和在開始治療前存在的變量（在 1,363 名參與者中）。
在這三項研究中，病毒治療失敗的匯總率為 1.4% 或每 100 人年追蹤 0.54 次。給藥時間方案之間的病毒學失敗沒有顯著差異：每 8 周而不是每 4 週接受一次卡博特韋/利匹韋林注射與更高的病毒學失敗風險無關。
出現了五個因素作為病毒學失敗的重要預測因素：利匹韋林 (rilpivirine) 抗藥性突變的存在； HIV-1 A6 或 A1 亞型；在開始治療 4 週後預測卡博特韋(cabotegravir) 之濃度，並在開始治療 44 週後預測卡博特韋和利匹韋林濃度。
具有利匹韋林耐藥性突變的人發生病毒學失敗的風險是沒有利匹韋林耐藥性的人的 25 倍。攜帶 HIV-1 A6 亞型（俄羅斯和東歐最常見的 HIV 形式）或 A1（最初來自東非的亞型）的人病毒學失敗的風險高 15 倍（近 15% 的參與者患有疾病的這些亞型之一）。相比之下，低藥物濃度對病毒學失敗風險的影響要小得多。身體質量指數並未成為該分析中的重要因素，但 Orkin 指出，它與卡博特韋濃度高度相關。
僅查看開始治療前確定的因素，存在利匹韋林耐藥突變、HIV-1 A6 或 A1 亞型以及更高的身體質量指數可預測病毒學失敗。
在確定與病毒反彈或病毒學失敗相關的重要因素後，研究人員評估了哪些因素組合最能預測病毒失敗。
在三項研究期間接受卡博特韋和利匹韋林治療的 1,431 人中，有 970 人沒有基線之危險因素。該組中有四人 (0.4%) 經歷了病毒學失敗。
404 人存在一個基線之風險因素，該組中有 8 人 (2%) 經歷了病毒學失敗。
57 人存在兩個或更多基線風險因素，該組中有 11 人 (19%) 經歷了病毒學失敗。
在臨床實踐中使用這些預測因子需要注意患者的臨床病史，特別是任何非核苷反轉錄酶抑制劑(NNRTI) 的使用史，因為檢測存檔的 NNRTI 耐藥突變的 HIV 前病毒 DNA 測序並不是常規進行的。
Orkin 教授強調了仔細尋找多種因素存在的重要性，並強調與沒有預測因素相比，單獨一個因素並不會帶來更高的病毒學失敗風險。
參考文獻：
Orkin C et al. 擴展多變量模型以幫助患者選擇長效卡博特韋+利匹韋林治療：在超過 152 週後患者、藥物濃度和與病毒學失敗相關的病毒因素組合的臨床效用。國際愛滋病毒感染藥物治療大會（格拉斯哥愛滋病毒會議），摘要 O44，2022 年。
Who is at risk of injectable treatment failure?
Keith Alcorn / 1 November 2022 / aidsmap
Professor Chloe Orkin presenting at HIV Glasgow 2022. Image by Alan Donaldson Photography.
Three factors present before starting the combination strongly predict virologic failure of injectable antiretroviral treatment with cabotegravir and rilpivirine, Professor Chloe Orkin of Queen Mary University of London reported at the International Congress on Drug Therapy in HIV Infection (HIV Glasgow) last week. These factors can be used to identify people with HIV at higher risk of experiencing the failure of this regimen.
Although failure of the injectable cabotegravir/rilpivirine regimen was rare in clinical trials, affecting only 1.4% of participants, predicting who is less likely to benefit from the regimen can prevent treatment failure and the development of resistance. This is especially important in the case of injectable cabotegravir/rilpivirine, because these long-acting formulations remain in the blood for a long time, potentially reinforcing the emergence of resistance.
Investigators on the phase III clinical trials that led to the licensing of injectable cabotegravir/rilpivirine carried out an analysis of trial data from three studies to identify risk factors for virological failure throughout the study periods.
At HIV Glasgow 2022, Professor Chloe Orkin talks about who is at risk of injectable treatment failure.
The analysis pooled data from the ATLAS study (to week 96), the FLAIR study (to week 124) and the ATLAS-2M study (to week 152). Two sets of factors were analysed: variables measure both before starting the regimen and during treatment (in 1224 participants with complete study data) and variables present before starting the regimen (in 1363 participants).
During the three studies, the pooled rate of viral failure was 1.4% or 0.54 per 100 person-years of follow-up. There was no significant difference in viral failure between dosing regimens: receiving cabotegravir/rilpivirine injections every eight weeks rather than every four weeks was not associated with a higher risk of viral failure.
Five factors emerged as significant predictors of viral failure: the presence of rilpivirine resistant mutations; HIV-1 A6 or A1 subtype; predicted cabotegravir trough concentration four weeks after starting treatment and predicted cabotegravir and rilpivirine concentrations 44 weeks after starting treatment.
People with rilpivirine resistance mutations had a 25-times greater risk of viral failure than those without rilpivirine resistance. People with the HIV-1 A6 subtype, the most common form of HIV in Russia and eastern Europe, or A1, a subtype originally from east Africa, had a 15-times higher risk of viral failure (nearly 15% of participants had one of these subtypes). In comparison, low drug concentrations had a much smaller impact on the risk of viral failure. Body mass index did not emerge as a significant factor in this analysis, but Orkin noted that it is highly correlated with cabotegravir concentrations.
Looking only at factors identified before starting treatment, the presence of rilpivirine resistant mutations, HIV-1 A6 or A1 subtype and greater body mass index predicted viral failure.
After identifying the significant factors associated with viral rebound or viral failure, the investigators assessed which combinations of factors best predicted viral failure.
In 1431 people who received cabotegravir and rilpivirine during the three studies, 970 people had no baseline risk factors. Four people (0.4%) experienced viral failure in this group.
One baseline risk factor was present in 404 people and eight people (2%) experienced viral failure in this group.
Two or more baseline factors were present in 57 people and 11 people (19%) in this group experienced viral failure.
Using these predictors in clinical practice will require attention to a patient’s clinical history, in particular any history of NNRTI use, as sequencing of HIV proviral DNA to detect archived NNRTI drug resistance mutations is not carried out routinely.
Professor Orkin highlighted the importance of looking carefully for the presence of multiple factors and stressed that one factor alone did not confer a higher risk of viral failure than the absence of predictive factors.
References
Orkin C et al. Expanded multivariable models to assist patient selection for long-acting cabotegravir+rilpivirine treatment: clinical utility of a combination of patient, drug concentration, and viral factors associated with virological failure over 152 weeks. International Congress on Drug Therapy in HIV Infection (HIV Glasgow), abstract O44, 2022.