*Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY; †The Rockefeller University, New York, NY; and ‡Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Solna, Sweden (Dr Palmer is now with the Westmead Millennium Institute for Medical Research and University of Sydney, Westmead, New South Wales, Australia).
J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):140-7. doi: 10.1097/QAI.0000000000000111.
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 with similarly applied 3-drug PI-based cART.
Forty newly HIV-1-infected patients were randomized 1:2 to receive 3-drug (N = 14) or 5-drug (N = 26) therapy. The primary end point was the percent of subjects with undetectable plasma viremia using standard reverse transcriptase-polymerase chain reaction and the single copy assay after 48 weeks. Secondary end points 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 reverse transcriptase-polymerase chain reaction and single copy assay (P = 0.46, Fisher 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 infectious units per million, 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.
为了了解是否已经优化了联合抗逆转录病毒治疗（cART），我们研究了在早期感染时，用拉替拉韦和马拉维若强化的 3 药蛋白酶抑制剂（PI）为基础的 cART 是否比同样应用的 3 药 PI 为基础的 cART 有更好的疗效。
40 例新感染 HIV-1 的患者被随机分为 1:2 接受 3 药（N=14）或 5 药（N=26）治疗。主要终点是 48 周后用标准逆转录酶-聚合酶链反应和单拷贝法检测不可测的血浆病毒载量的患者比例。次要终点包括细胞相关 HIV-1 DNA 和 RNA 水平，以及 96 周时静止 CD4 T 细胞中感染性病毒水平，以及定量和定性免疫反应。
48 周时，34 例患者仍在研究中，并被纳入治疗分析。3 药组 11 例中 3 例（27.3%）和 5 药组 21 例中 9 例（42.9%）的血浆 HIV-1 RNA 水平均低于标准逆转录酶-聚合酶链反应和单拷贝法的检测下限（P=0.46，Fisher 确切检验）。在 96 周的治疗过程中，未见前病毒 DNA的绝对水平或细胞相关 RNA 的变化有显著差异。在 7 例用 3 药和 13 例用 5 药治疗的患者中，在第 96 周时，静止 CD4 T 细胞中感染性 HIV-1 的平均水平分别为 0.67 和 0.71 感染单位/百万个细胞（P=0.81）。在定量或定性免疫测定中，包括免疫激活标志物，均未见差异。
在早期感染时强化的 5 药 cART 并不能显著提高病毒学或免疫反应，超过标准的 3 药 PI 为基础的 cART。
