Intensifying Antiretroviral Therapy With Raltegravir and Maraviroc During Early Human Immunodeficiency Virus (HIV) Infection Does Not Accelerate HIV Reservoir Reduction.
Intensifying Antiretroviral Therapy With Raltegravir and Maraviroc During Early Human Immunodeficiency Virus (HIV) Infection Does Not Accelerate HIV Reservoir Reduction.
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DOI：
10.1093/ofid/ofv138
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发表时间：
2015-12
影响因子：
4.2
通讯作者：
Kovacs C
中科院分区：
文献类型：
--
作者：
Ostrowski M;Benko E;Yue FY;Kim CJ;Huibner S;Lee T;Singer J;Pankovich J;Laeyendecker O;Kaul R;Kandel G;Kovacs C
背景。CD4+ t细胞库中的持久性人类免疫缺陷病毒（HIV）是根除的障碍。我们假设，在早期HIV感染期间，在标准联合抗逆转录病毒治疗（cART）中加入雷替格拉韦和马拉韦洛克可以大大减少病毒库，从而实现根除。方法。一项前瞻性、随机、双盲、安慰剂对照试验招募了32名记录早期（<6个月）HIV感染的参与者，他们要么接受标准cART（恩曲他滨/替诺福韦/洛匹那韦/利托那韦），要么接受强化cART（标准方案+雷替格拉韦/马拉韦）。人类免疫缺陷病毒库在基线和48周时通过(1)原病毒DNA，(2)细胞相关RNA，(3)复制能力病毒（均来自纯化的血液CD4+ T细胞）和(4)肠道原病毒DNA进行评估。一种基于基线血清的多分析算法（MAA）估计感染时间。结果。30人完成了48周的研究。血液前病毒负荷的减少为- 1.03 log DNA拷贝/106 CD4+ T细胞。标准组和强化组分别为84例（P = 0.056）。总的来说，在48周内，HIV相关RNA、血液CD4+ T细胞中的复制能力病毒和前肠道HIV DNA的下降速度没有显著差异。最近出现HIV感染的个体具有明显较低的病毒库，而cART倾向于在更大程度上降低其病毒库。结论。与标准cART相比，强化cART在48周时没有导致血液病毒库的额外减少。在HIV感染早期，人类免疫缺陷病毒库的大小较小。将需要其他新的治疗策略结合早期cART来消除HIV潜伏库。
Background. Persistent human immunodeficiency virus (HIV) within the CD4+ T-cell reservoir is an obstacle to eradication. We hypothesized that adding raltegravir and maraviroc to standard combination antiretroviral therapy (cART) during early HIV infection could substantially reduce viral reservoirs as a step towards eradication. Methods. A prospective, randomized, double-blinded, placebo-controlled pilot trial enrolled 32 participants with documented early (<6 months) HIV infection to either standard cART (emtricitabine/tenofovir/lopinavir/ritonavir) or intensive cART (standard regimen + raltegravir/maraviroc). Human immunodeficiency virus reservoirs were assessed at baseline and at 48 weeks by (1) proviral DNA, (2) cell-associated RNA, and (3) replication-competent virus, all from purified blood CD4+ T cells, and (4) gut proviral DNA. A multiassay algorithm (MAA) on baseline sera estimated timing of infection. Results. Thirty individuals completed the study to the 48-week endpoint. The reduction in blood proviral burden was −1.03 log DNA copies/106 CD4+ T cells versus −.84 log in the standard and intensive groups, respectively (P = .056). Overall, there was no significant difference in the rate of decline of HIV-associated RNA, replication-competent virus in blood CD4+ T cells, nor proviral gut HIV DNA to 48 weeks. Individuals who presented with more recent HIV infection had significantly lower virus reservoirs, and cART tended to reduce their reservoirs to a greater extent. Conclusions. Intensive cART led to no additional reduction in the blood virus reservoir at 48 weeks compared with standard cART. Human immunodeficiency virus reservoir size is smaller earlier in HIV infection. Other novel treatment strategies in combination with early cART will be needed to eliminate the HIV latent reservoir.