於高CD4細胞計數時開始抗病毒藥劑治療( ART )對於病毒載量低的人來說具有明顯的益處
資料來源：Michael Carter; 2019年7月10日，aidsmap news，財團法人台灣紅絲帶基金會編譯
根據發表於「後天免疫缺乏症候群雜誌」大型治療的初始研究結果分析，開始抗反轉錄病毒治療（ART）具有顯著的益處，並且對治療前病毒載量低的個體幾乎沒有風險。 ART的迅速啟動與CD4細胞計數的強烈增加，持續的病毒抑制和炎性生物指標的有利變化相關。調查人員還計算出在透過幾乎消除了愛滋病毒向外傳播的風險，治療將對公共衛生有益。
該研究涉及將病毒載量低於3000拷貝/亳升基準線的患者招募至START（(Strategic Timing of Antiretroviral Treatment，策略性時間的抗反轉錄病毒治療）研究中。這明確地確定了ART對CD4細胞計數較高（500細胞/ 立方毫米以上）患者的益處。世界各地的治療指南現在都是無論CD4細胞計數如何，均推薦所有人使用ART。然而，即使不使用抗反轉錄病毒治療，少數愛滋病毒感染者的病毒載量仍然很低，因此有人質疑抗病毒治療是否必要。 START研究的研究人員檢查了他們的數據，看看這些患者是否從治療中獲益。
共有4684名HIV陽性成年患者被招募進入該研究。所有患者的CD4細胞計數均高於500個細胞/ 立方毫米，隨機分組進入到立即開始進行抗反轉錄病毒治療組或直至其CD4細胞計數降低至低於此水平的延遲治療組中。目前的分析僅限於1134個人（佔研究總人口的25％），其治療前病毒載量低於3000拷貝/亳升。
研究人員比較了直接和延期ART組之間的臨床結果（包括非HIV相關的嚴重疾病、住院治療和全死因死亡率），病毒載量，CD4細胞計數和生物指標（包括那些指示發炎現象的指標）。
CD4細胞計數之中位基線為714個細胞/ 立方亳米，平均年齡為37歲，大多數參與者（60％）為男性。一小組患者（n = 93）的治療前病毒載量低於50拷貝/ ml。而隨機分派至至即時（n = 555）或延期治療（n = 579）的參與者人數幾乎相等。
在64名直接治療患者和61名延遲治療患者中觀察到嚴重的臨床結果，並無顯著差異。
即時的治療在病毒抑制方面具有明顯的益處。在追蹤12個月後，有93％的立即治療患者相較於有22％的延遲治療組患者，其病毒載量低於200拷貝/亳升。有證據顯示，如果沒有ART，病毒載量抑制低於50拷貝/ ml將無法維持。在追蹤的第一年，於延遲治療組原本基線病毒載量低於50拷貝/ 亳升的患者當中有55％經歷到其病毒血症增加超過該水平。
立即開始接受抗反轉錄病毒治療的患者其CD4細胞計數增加，但延遲治療的患者其CD4細胞計數則下降。追蹤12個月後，直接ART組的平均CD4細胞計數高出125個細胞/ 立方毫米，到第36個月時，平均差異增加到235個細胞/立方毫米。儘管如此，無論其研究組別，在基線病毒載量低於50拷貝/毫升的患者亞組當中，其CD4細胞計數則保持穩定。
直接組和延遲組兩者間在三年的追蹤後，其血紅蛋白、血小板計數、血清肌酸酐（Creatinine，註：檢測腎功能指標）、ALT（註：肝發炎指數）和腎功能等經歷嚴重變化的比例，幾乎沒有差異。
然而，在即時研究組中有一些顯示系統性發炎狀態的生物指標中存在著有益的變化，但在推遲治療的患者中則沒有。而在基線病毒載量低於50拷貝/毫升的亞組中，則這些差異並不顯著。
最後，經計算立即治療顯著的具有公共衛生益處。研究人員估計，超過12個月，直接組中每100名患者的HIV向外傳播率為0.2，而延遲組則每100名患者為3.2。
即使本研究中僅有93名患者在治療前病毒載量低於50拷貝/毫升，Irini Sereti博士及其同事表示，這仍是迄今為止涵括這些個案之最大的隨機研究。對於該群個案，沒有觀察到立即開始抗反轉錄病毒治療的明顯臨床益處，但也沒有出現傷害的證據。由於臨床試驗並沒有為如何治療具有這種罕見疾病表型的個體提供明確的指導，他們建議臨床決策時應與患者基於伙伴關係並予以個人化考量。
「最後總結來說」，作者寫道，「對於大多數HIV RNA低於3000拷貝/毫升的愛滋病毒陽性族群，儘管很少會有臨床上的事件，但我們的分析顯示，即刻開始抗反轉錄病毒療法導致HIV RNA被抑制，CD4細胞計數增加，且幾乎沒有證據顯示嚴重臨床結果增加，而愛滋病毒向外傳播之比率亦有適度的下降」。
Starting ART at a high CD4 cell count has clear benefits for people with a low viral load
Michael Carter; 10 July 2019
Starting antiretroviral therapy (ART) has significant benefits and entails few risks for individuals with a low pre-treatment viral load, according to analysis of results from a large treatment initiation study published in the Journal of Acquired Immune Deficiency Syndromes. Prompt initiation of ART was associated with robust increases in CD4 cell count, sustained viral suppression and favourable changes in inflammatory biomarkers. The investigators also calculated that treatment would have public health benefits by almost eliminating the risk of onward HIV transmission.
The study involved patients with a baseline viral load below 3000 copies/ml recruited to the START(Strategic Timing of Antiretroviral Treatment) study. This unequivocally established the benefits of ART for patients with higher CD4 cell counts (above 500 cells/mm3). Treatment guidelines around the world now recommend ART for all individuals, regardless of CD4 cell count.
However, a small number of individuals with HIV have a persistently low viral load even without the use of ART, leading some to question whether ART is necessary. Investigators from the START study examined their data to see if these patients benefit from therapy.
A total of 4684 adult HIV-positive patients were recruited to the study. All had a CD4 cell count above 500 cells/mm3 and were randomised to start immediate ART or to defer therapy until their CD4 cell count fell below this level.The current analysis was restricted to the 1134 individuals (25% of the total study population) who had a pre-treatment viral load below 3000 copies/ml.
The investigators compared clinical outcomes (serious non-HIV-related illnesses, hospitalisations and all-cause mortality), viral load, CD4 cell count and biomarkers (including those indicating inflammation) between the immediate and deferred ART groups.
The median baseline CD4 cell count was 714 cells/mm3, average age was 37 years and the majority of participants (60%) were male. A small sub-set of patients (n = 93) had a pre-treatment viral load below 50 copies/ml.
Participants were almost equally randomised to immediate (n = 555) or deferred therapy (n = 579).
A serious clinical outcome was observed in 64 patients in the immediate and 61 patients in the deferred group, a non-significant difference.
Immediate therapy had clear benefits in terms of viral suppression. After twelve months of follow-up, 93% of patients in the immediate compared to 22% of those in the deferred group had a viral load below 200 copies/ml. There was evidence that viral load suppression below 50 copies/ml would not be maintained without ART. During the first year of follow-up, 55% of individuals in the deferred group with a baseline viral load below 50 copies/ml experienced an increase in viraemia above this level.
CD4 cell counts increased among the patients who started immediate ART but declined among the patients deferring treatment. After twelve months of follow-up, mean CD4 cell count was 125 cells/mm3 higher in the immediate ART group and by month 36 this had increased to a mean difference was 235 cells/mm3. Nonetheless, regardless of study arm, CD4 cell count remained stable in the sub-group of patients with a baseline viral load below 50 copies/ml.
There was little difference over three years of follow-up between the immediate and deferred groups in the proportion experiencing serious changes in haemoglobin, platelet count, creatinine, ALT and kidney function.
However, there were beneficial changes in several biomarkers indicating systemic inflammation in the immediate study arm, but not among patients who deferred treatment. In the sub-group with a baseline viral load below 50 copies/ml, these differences were not significant.
Finally, immediate treatment was calculated to have significant public health benefits. The investigators estimated that over twelve months the rate of onward HIV transmission would be 0.2 per 100 patients in the immediate group but 3.2 per 100 patients in the deferred group.
Even with just 93 individuals with a pre-treatment viral load below 50 copies/ml included, Dr Irini Sereti and colleagues say that this is the largest randomised study of such individuals to date. For this group, a clear clinical benefit to starting ART was not observed, but neither was there evidence of harm. As clinical trials do not provide clear guidance on how to treat individuals with such rare disease phenotypes, they recommend that clinical decision making should be individualised and based on a partnership with the patient.
“In conclusion,” write the authors, “for most HIV-positive people with HIV RNA below 3000 copies/ml, although there are low numbers of clinical events, our analyses show that immediate ART results in suppressed HIV RNA, CD4 cell count increases, little evidence of increased serious clinical outcomes, and an estimated modest decrease in onward HIV transmission.”
References
Sereti I et al. ART in HIV-positive persons with low pre-treatment viremia: results from the START trial. J Acquir Immune Defic Syndr, 81: 456-62, doi: 10.1097/QAI.0000000000002052, 2019.