立即治療可能對近期感染愛滋病毒的人特別有益

 

立即治療可能對近期感染愛滋病毒的人特別有益

Keith Alcorn, aidsmap news, 發佈時間:201973日;財團法人台灣紅絲帶基金會編譯

 

由及時提供HIV治療的START研究之分析中發現,對於先前感染愛滋病毒不到6個月的人立即啟動抗反轉錄病毒藥物治療,對其CD4細胞之計數產生了最大的提升。該研究調查人員在7月份的愛滋病期刊中寫道,在近期感染愛滋病毒者中,早期治療的益處可能在START研究中被低估了。

START試驗的總體結果是,在CD4計數超過500個細胞/立方亳米時即開始治療,與延遲直至CD4計數降到350個細胞/ 立方亳米或愛滋病相關症狀已發展時才治療相比,發生愛滋病定義相關事件的風險降低了72%。

近期感染的人其CD4計數的更大提升將可保護其對抗愛滋相關的疾病。儘管START研究的目的不是根據感染持續的時間來觀察臨床結果上的差異(它需要更多的參與者才能進行這些比較),但研究人員能夠將CD4細胞計數上的變化視為替代標記。

START研究將CD4細胞計數超過500個細胞/立方毫米的4,684HIV成年感染者,隨機分配到立即開始治療組中,或是直到CD4計數降至350個細胞/立方毫米或HIV相關之症狀已經發展的推遲治療組中。

START研究中,有373人被歸類為近期感染(第1組)。他們要嘛在加入研究之前的六個月內自我報告感染了愛滋病毒,要不然便是在過去六個月內被診斷出感染愛滋病毒,並且有抗體標記顯示係近期感染了愛滋病毒。在已知感染日期的患者中,在暴露於HIV的時間和被隨機分配的時間,其期間的中位數時間為4.8個月。

 

近期感染HIV而並未立即進行治療的人特別容易受到HIV疾病進展的傷害

 

在研究中大多數研究參與者其感染愛滋病毒的時間為624個月(2,634人,第2組) 。另有1,605名參與者感染愛滋病毒至少兩年(第3組)。亦有72名參與者被排除在分析之外,由於樣本流失。

在基準線上,近期感染組的CD4細胞計數略高於其他組(660細胞/立方毫米,而第2組為654,第3組為644p = 0.007)。而他們的CD8 +細胞計數也較低,顯示在這一組中其免疫功能上有較高異常性。

近期感染組其病毒載量更有可能高於50,000拷貝/毫升以上,並且其病毒載量低於3,000拷貝/ 亳升的可能性亦顯著地低於其他組(均為p <0.001)。

在開始治療並平均追蹤3年後,立即治療組其平均CD4細胞增加高出194個細胞/ 立方亳米,但在近期感染組(增加231細胞)與第2和第3組相比之下差異更大(分別為增加202和增加171細胞/立方毫米,p <0.001)。近期感染組也經歷了CD4CD8比值更大幅的增加,顯示免疫功能更正常化。

在推遲治療的患者中,最近感染組的CD4細胞減少至<350細胞/立方毫米或發展成為愛滋病的比率更高。感染不到6個月者相較於其他感染至少兩年的人,當中有52%的人更容易達到前述任一的終點,(風險比為1.52 , 95%信賴區間 1.14 - 2.05),顯示近期感染HIV者若無立即治療則特別容易受到HIV疾病進展之傷害。在近期感染組中,其疾病進展的發生率為15.6/100追蹤人年,而在感染兩年或更長時間的人當中,則為10.5/100追蹤人年。

近期感染HIV者在進行即時治療或相對地延遲治療上,本START研究所發現的結果亦強化了另一SPARTAC研究的結果,研究顯示,被隨機被分派至於血清陽轉後不到12週便立即接受治療的患者,較不可能去經歷到CD4細胞衰減至低於350或因其他原因需要開始治療。

HIV感染後不久便開始治療可能特別具有保護作用。研究結果亦強調可以提供當天便開始治療之臨床服務的重要性,。

START的研究人員將繼續追踪參與者到2,021年,去檢視研究結果的長期影響,包括近期感染HIV之參與者其免疫上更大的恢復情況。

Immediate treatment is probably especially beneficial for people with recent HIV infection

Keith AlcornPublished: 03 July 2019

Immediate initiation of antiretroviral treatment produced the biggest boost in CD4 cell count for people infected with HIV less than six months previously, an analysis of the START study of prpt HIV treatment has found. Writing in the July issue of AIDS, the study investigators say that the benefit of early treatment for people with recent HIV infection may have been understated in START.

The START trial's overall finding was that starting treatment at a CD4 count above 500 cells/mm3 was associated with a 72% reduction in the risk of AIDS-defining events when compared to deferring treatment until a CD4 count of 350 cells/mm3 was reached or HIV-related symptoms developed.

A greater CD4 count increase in people with recent infection might protect against HIV-related illness. Although the START study was not designed to look at differences in clinical outcomes according to duration of infection (it would have needed many more participants to carry out these comparisons), investigators were able to look at changes in CD4 cell count as a surrogate marker.

The START study randomised 4684 adults living with HIV with CD4 cell counts above 500 cells/mm3 to start treatment immediately or defer treatment until a CD4 count of 350 cells/mm3 was reached or HIV-related symptoms.

 

In START, 373 people were classified as recently infected (Group 1). They either self-reported acquiring HIV within the six months prior to joining the study or had been diagnosed with HIV in the previous six months and had antibody markers that indicated recent HIV infection. Of those with a known infection date, the median time between exposure to HIV and randomisation in the study was 4.8 months.

People with early HIV infection are especially vulnerable to HIV disease progression without immediate treatment. 

The majority of study participants had been living with HIV for between 6 and 24 months (2634 persons, Group 2). A further 1605 participants had been living with HIV for at least two years (Group 3). Seventy-two participants were excluded from the analysis owing to missing samples.

At baseline the recently-infected group had slightly higher CD4 cell counts than the other groups (660 cells/mm3 compared to 654 in Group 2 and 644 in Group 3 (p=0.007). They also had lower CD8+ cell counts, indicating greater abnormality in immune function in this group.

The recently-infected group were significantly more likely to have a viral load above 50,000 copies/ml and significantly less likely to have a viral load below 3,000 copies/ml (both p<0.001) than the other groups.

After starting treatment, the mean CD4 cell gain was 194 cells/mm3 higher in the immediate treatment group after an average follow-up of three years, but this difference was greater in the recently-infected group (+231 cells) compared to groups 2 and 3 (+202 and +171 cells/mm3 respectively, p< 0.001). The recently-infected group also experienced greater increase in CD4:CD8 ratio, indicating greater normalisation of immune function.

In those who deferred treatment, the rate of CD4 cell decline to <350 cells/mm3 or development of AIDS was greater in the recently-infected group. People infected for less than six months were 52% more likely to reach one of these endpoints than people infected for at least two years (HR 1.52, 95% CI 1.14-2.05), showing that people with early HIV infection are especially vulnerable to HIV disease progression without immediate treatment. The incidence of disease progression was 15.6 per 100 person-years of follow-up in the recently-infected group compared to 10.5 per 100 person-years in those infected for two years or more.

 

The findings from the START study reinforce the findings of the SPARTAC study of immediate versus deferred treatment in early HIV infection, which showed that people randomised to immediate treatment less than 12 weeks after seroconversion were less likely to experience a CD4 cell decline below 350 or need to start treatment for other reasons.

Starting treatment soon after HIV infection may be especially protective. The study findings emphasise the importance of clinical services which can offer same-day treatment initiation.

START investigators will continue to follow participants to 2021 to look at the long-term implications of the study findings, including the greater immunological recovery in recently-infected participants.

Reference

Sharma S et al. The benefit of immediate compared with deferred antiretroviral therapy on CD4+ cell count recovery in early HIV infection. AIDS, 33: 1335-44, 2019.