A randomized open-label study of 3- versus 5-drug combination antiretroviral therapy in newly HIV-1-infected individuals.
A randomized open-label study of 3- versus 5-drug combination antiretroviral therapy in newly HIV-1-infected individuals.
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对新近HIV-1感染的个体的3-药物组合抗逆转录病毒疗法的随机开放标签研究。
DOI：
10.1097/qai.0000000000000111
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发表时间：
2014-06-01
期刊：
影响因子：
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通讯作者：
Mohri H
中科院分区：
文献类型：
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作者：
Markowitz M;Evering TH;Garmon D;Caskey M;La Mar M;Rodriguez K;Sahi V;Palmer S;Prada N;Mohri H
为了了解联合抗逆转录病毒治疗（cART）是否已经优化，我们询问了与类似应用的基于3种药物蛋白酶抑制剂（PI）的cART相比，在早期感染期间使用雷特格韦和马拉韦罗强化并启动的基于3种药物蛋白酶抑制剂（PI）的cART是否会改善结局。将40例HIV-1新发感染者按1：2随机分为3药组（N=14）和5药组（N=26）。主要终点是48周后使用标准RT-PCR和单拷贝测定（SCA）检测不到血浆病毒血症的受试者百分比。次要终点包括第96周时细胞相关HIV-1 DNA和RNA水平、静息CD 4 + T细胞中感染性病毒水平以及定量和定性免疫应答。第48周时，34例受试者仍在研究中，并纳入实际治疗分析。3种药物组11例患者中的3例（27.3%）和5种药物组21例患者中的9例（42.9%）血浆HIV-1 RNA水平均低于标准RT-PCR和SCA检测值（P= 0.46，Fisher精确检验）。在96周的治疗期间，前病毒DNA的绝对水平或细胞相关RNA的变化没有显著差异。第96周，7例接受3种药物治疗的受试者和13例接受5种药物治疗的受试者的静息CD 4 + T细胞中的感染性HIV-1平均水平分别为0.67和0.71 IUPM（P= 0.81）。在定量或定性免疫学测定（包括免疫活化标志物）中未观察到差异。在早期感染期间启动的强化5种药物cART未能显著进一步影响病毒学或免疫学应答，超过标准的基于3种药物PI的cART所实现的应答。
To understand whether combination antiretroviral therapy (cART) has been optimized, we asked whether 3-drug protease inhibitor (PI)-based cART intensified with raltegravir and maraviroc and initiated during early infection would improve outcomes when compared to similarly applied 3-drug PI-based cART. 40 newly HIV-1 infected patients were randomized 1:2 to receive 3-drug (N=14) or 5-drug (N=26) therapy. The primary endpoint was the percent of subjects with undetectable plasma viremia using standard RT-PCR and the single copy assay (SCA) after 48 weeks. Secondary endpoints included levels of cell-associated HIV-1 DNA and RNA and levels of infectious virus in resting CD4+ T cells at week 96 and quantitative and qualitative immunologic responses. At 48 weeks, 34 subjects remained on study and are included in the as-treated analysis. Three of 11 (27.3%) in the 3-drug arm and 9 of 21 (42.9%) in the 5-drug arm had plasma HIV-1 RNA levels below detection by both standard RT-PCR and SCA (P= 0.46, Fishers exact test). No significant differences in absolute levels of proviral DNA or changes in cell-associated RNA were seen during 96-weeks of therapy. Mean levels of infectious HIV-1 in resting CD4+ T cells at week 96 in 7 subjects treated with 3-drugs and 13 with 5-drugs were 0.67 and 0.71 IUPM respectively (P= 0.81). No differences were seen in quantitative or qualitative immunologic determinations including markers of immune activation. Intensified 5-drug cART initiated during early infection fails to significantly further impact virologic or immunologic responses beyond those achieved with standard 3-drug PI-based cART.