在病毒反彈後，以多替拉韋為基礎 (dolutegravir-based) 的治療更有可能抑制 HIV
資料來源：基思·奧爾康 / 2022 年 10 月 31 日 /aidsmap / 則財團法人台灣紅絲帶基金會編譯
Andrew Hill 博士在 HIV Glasgow 2022 上發表演講。圖片來自 Alan Donaldson Photography。
一項對四項大型臨床試驗的薈萃分析報告說，與含有依非韋倫 (efavirenz) 的治療相比，基於 Dolutegravir 的治療更可能導致病毒反彈後對 HIV 的重新抑制。
利物浦大學的 Andrew Hill 博士本週在國際愛滋病毒感染藥物治療大會（格拉斯哥愛滋病毒）上介紹了這些發現。
在病毒反彈至檢測限制以上後，抗反轉錄病毒治療方案重新抑制 HIV 的能力對於可用治療方案數量有限的中、低收入環境來說是一個特別重要的問題。
如果一線治療失敗，二線治療的費用要高得多，因此根據世界衛生組織的指導方針，在病毒性反彈的管理上，了解當人們繼續使用現有的治療方案並接受強化的順從性諮詢時，病毒再抑制的可能性至關重要。
這個問題在二線治療中變得更加關鍵，因為替代治療的選擇較少。
推薦基於多替拉韋 ( Dolutegravir) 的治療作為一線治療的首選方案，因為它具有較高的耐藥屏障。且與基於依非韋倫 (efavirenz) 的治療相比，多替拉韋治療的耐受性也更好。
為了評估基於 dolutegravir 的治療是否更有可能在病毒反彈後導致 HIV 的重新抑制，研究人員匯總了來自四項大型研究的數據，這些研究將 dolutegravir 與基於依非韋倫 (efavirenz) 或基於蛋白酶抑製劑的治療在撒哈拉以南非洲進行了比較。
分析中包括的研究是：
• ADVANCE，在南非以前未經治療的人群中進行，對多替拉韋或依非韋倫與替諾福韋/恩曲他濱(tenofovir/emtricitabine) 抑或是與替諾福韋艾拉酚胺/恩曲他濱 (tenofovir alafenamide/emtricitabine) 相配對的比較。
• NAMSAL，在喀麥隆針對以前未經治療的人群中進行，對多替拉韋或低劑量依非韋倫與替諾福韋/拉米夫定 (tenofovir/lamivudine) 配對的比較。
• DOLPHIN-2，在烏干達以前未經治療的孕婦中進行，多替拉韋和依非韋倫與替諾福韋/拉米夫定(tenofovir/lamivudine) 配對的比較。
• VISEND，在轉換到含有多替拉韋或增強型蛋白酶抑製劑的二線治療時比較幾種 NRTI 之組合。
該分析觀察了四項研究中經歷過病毒失敗（第 24 週後病毒載量超過 1000 個拷貝）且未改變治療的參與者的病毒再抑制率。病毒失敗的參與者可以被歸類為HIV重新抑制、病毒水平持續高於 1000 拷貝或失訪。
在 ADVANCE 中，三個研究組的病毒失敗率相似（8-13%），但再抑制率從依非韋倫 (efavirenz) 研究組的 23% 到多替拉韋 (dolutegravir) 組的 41% 和 59% 不等。同樣的模式在 NAMSAL 中也很明顯。兩個研究組中 15% 和 17% 的人經歷了病毒失敗，而多替拉韋組中 60% 的人重新抑制了病毒載量，而依非韋倫組中只有 27% 的人這樣做了。
在 VISEND 中，病毒載量高於 1,000 拷貝/ml 的人比基準線病毒載量低於 1,000 拷貝/ml 的人更有可能經歷病毒失敗。加強型蛋白酶抑製劑研究組 (20-27%) 比多替拉韋組 (12% – 18%) 更常發生病毒失敗。與多替拉韋組 (34-41%) 相比，增強型蛋白酶抑製劑組 (17-19%) 的再抑制發生率較低。
在 DOLPHIN-2 中，多替拉韋 (dolutegravir) 和依非韋倫 (efavirenz) 組之間的病毒失敗和再抑制沒有顯著差異。
在薈萃分析中，多替拉韋的病毒再抑制率顯著高於依非韋倫（p=0.04）。
在四項研究中的三項中，在持續性病毒血症高於 1,000 拷貝/ml的病毒學失敗患者中未接受多替拉韋治療者更為常見。例如，在 ADVANCE 中，52% 的依非韋倫組病毒失敗者在研究第 24 週後病毒載量持續高於 1,000 拷貝/毫升，而在多替拉韋組中這一比例為 14% 和 27%。在 NAMSAL 和 VISEND 中看到了相同的模式，但在 DOLPHIN-2 中沒有。
Andrew Hill 博士在介紹研究結果時說，需要進行更多的研究來評估在轉向服用 dolutegravir 的人提供新方案之前需要多少順從性的諮詢和持續性的病毒血症。他指出，新的南非治療指南僅在檢測到整合酶抑製劑耐藥性時才建議從多替拉韋轉換。
開普敦大學 Desmond Tutu HIV 中心的 Linda-Gail Bekker 教授說，需要對使用 dolutegravir 重新抑制病毒載量的人進行長期追蹤。她詢問重新抑制的人是否最終在 dolutegravir 上仍失敗，正如之前基於 NNRTI 的治療所顯示的那樣。
參考文獻：
Hill A et al. 在 3,116 名參與者中進行的四項多替拉韋、依非韋倫或蛋白酶抑製劑治療隨機試驗中的病毒學失敗和 HIV RNA 的再抑制率。國際愛滋病毒感染藥物治療大會（格拉斯哥愛滋病毒），格拉斯哥，摘要 O42，2022 年。
After viral rebound, dolutegravir-based treatment more likely to suppress HIV
Keith Alcorn / 31 October 2022 / aidsmap
Dr Andrew Hill presenting at HIV Glasgow 2022. Image by Alan Donaldson Photography.
Dolutegravir-based treatment is significantly more likely to result in re-suppression of HIV after viral rebound than treatment containing efavirenz, a meta-analysis of four large clinical trials has reported.
The findings were presented this week at the International Congress on Drug Therapy in HIV Infection (HIV Glasgow) by Dr Andrew Hill of Liverpool University.
The capacity of an antiretroviral regimen to re-suppress HIV after viral rebound above the limit of detection is an especially important question for lower- and middle-income settings where a limited number of regimens are available.
If first-line treatment fails, second-line treatment is considerably more expensive, so it is critical to understand the likelihood of viral re-suppression when people continue with their existing regimen and receive enhanced adherence counselling, in line with World Health Organization guidelines for the management of viral rebound.
The question becomes even more critical in second-line treatment, where options for replacement treatment are fewer.
Dolutegravir-based treatment is recommended as a preferred option for first-line treatment due to its high barrier to resistance. Treatment with dolutegravir is also better tolerated than efavirenz-based treatment.
To evaluate whether dolutegravir-based treatment is more likely to lead to re-suppression of HIV after viral rebound, investigators pooled data from four large studies that compared dolutegravir to efavirenz-based or protease inhibitor-based treatment in sub-Saharan Africa.
The studies included in the analysis were:
•ADVANCE, a comparison of dolutegravir or efavirenz, paired with either tenofovir/emtricitabine or tenofovir alafenamide/emtricitabine, carried out in previously untreated people in South Africa
•NAMSAL, a comparison of dolutegravir or lower-dose efavirenz, paired with tenofovir/lamivudine, carried out in previously untreated people in Cameroon
•DOLPHIN-2, a comparison of dolutegravir and efavirenz, paired with tenofovir/lamivudine, carried out in previously untreated pregnant women in Uganda
•VISEND, a comparison of several NRTI combinations when switching to second-line treatment containing dolutegravir or a boosted protease inhibitor
The analysis looked at viral re-suppression rates in participants in the four studies who had experienced viral failure (a viral load above 1000 copies after week 24) and did not change treatment. Participants with viral failure could be classified either as re-suppressing HIV, having persistent virus levels above 1000 copies or lost to follow-up.
In ADVANCE, viral failure rates were similar across the three study arms (8-13%) but re-suppression rates ranged from 23% in the efavirenz study arm to 41% and 59% in the dolutegravir arms. The same pattern was evident in NAMSAL; 15% and 17% experienced viral failure in the two study arms but whereas 60% in the dolutegravir arm re-suppressed viral load, only 27% in the efavirenz arm did so.
In VISEND, people who entered the study with viral load above 1,000 copies/ml were more likely to experienced viral failure than those with baseline viral load below 1,000 copies/ml. Viral failure occurred more often in the boosted protease inhibitor study arms (20-27%) than in the dolutegravir arms (12% – 18%). Re-suppression occurred less often in the boosted protease inhibitor arms (17-19%) than in the dolutegravir arms (34-41%).
In DOLPHIN-2, viral failure and re-suppression did not differ substantially between the dolutegravir and efavirenz arms.
In the meta-analysis, the rate of viral re-suppression was significantly higher for dolutegravir than efavirenz (p=0.04).
In three of the four studies, sustained viraemia above 1,000 copies/ml was more common in those with viral failure who did not receive dolutegravir. For example, in ADVANCE, 52% of those with viral failure in the efavirenz arm had a sustained viral load above 1,000 copies/ml after week 24 of the study, compared with 14% and 27% in the dolutegravir arms. The same pattern was seen in NAMSAL and VISEND, but not in DOLPHIN-2.
Presenting the study findings, Dr Andrew Hill said that more research was needed to assess how much adherence counselling and sustained viraemia are required before people taking dolutegravir are offered a new regimen. He pointed out that new South African treatment guidelines only recommend a switch from dolutegravir if integrase inhibitor resistance is detected.
Professor Linda-Gail Bekker of the Desmond Tutu HIV Centre at the University of Cape Town said that long-term follow-up of people who re-suppress viral load on dolutegravir is needed. She asked whether people who re-suppress ultimately fail on dolutegravir, as has been previously shown for NNRTI-based treatment.
References
Hill A et al. Virological failure and HIV RNA re-suppression rates in four randomised trials of dolutegravir, efavirenz or protease inhibitor-based treatment in 3116 participants. International Congress on Drug Therapy in HIV Infection (HIV Glasgow), Glasgow, abstract O42, 2022.