Puertas Maria C, Massanella Marta, Llibre Josep M, Ballestero Monica, Buzon Maria J, Ouchi Dan, Esteve Anna, Boix Jaume, Manzardo Christian, Miró Josep M, Gatell Josep M, Clotet Bonaventura, Blanco Julià, Martinez-Picado Javier
aAIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona b'Lluita contra la SIDA' Foundation, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona cCenter for Epidemiological Studies on STI and HIV/AIDS of Catalonia dHospital Universitari Germans Trias i Pujol, Badalona eHospital Clinic - IDIBAPS, University of Barcelona fCatalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. *Maria C. Puertas, Marta Massanella, and Josep M. Llibre have contributed equally to the writing of this article.
AIDS. 2014 Jan 28;28(3):325-34. doi: 10.1097/QAD.0000000000000066.
Latent HIV-1-infected cells generated early in the infection are responsible for viral persistence, and we hypothesized that addition of maraviroc to triple therapy in patients recently infected with HIV-1 could accelerate decay of the viral reservoir.
Patients recently infected (<24 weeks) by chemokine receptor 5 (CCR5)-using HIV-1 were randomized to a raltegravir + tenofovir/emtricitabine regimen (control arm, n = 15) or the same regimen intensified with maraviroc (+MVC arm, n = 15). Plasma viral load, cell-associated HIV-1 DNA (total, integrated, and episomal), and activation/inflammation markers were measured longitudinally.
Plasma viral load decayed in both groups, reaching similar residual levels at week 48. Total cell-associated HIV-1 DNA also decreased in both groups during the first month, although subsequently at a slightly faster rate in the +MVC arm. The transient increase in two long terminal repeat (2-LTR) circles observed in both groups early after initiation of treatment decreased earlier in MVC-treated individuals. Early (week 12) increase of CD4 T-cell counts was higher in the +MVC arm. Conversely, CD8 T-cell counts and CD4 T-cell activation decreased slower in the +MVC arm. Absolute CD4 T-cell and CD8 T-cell counts, immune activation, CD4/CD8 T-cell ratio, and soluble inflammation markers were similar in both arms at the end of the study.
Addition of maraviroc in early integrase inhibitor-based treatment of HIV-1 infection results in faster reduction of 2-LTR newly infected cells and recovery of CD4 T-cell counts, and a modest reduction in total reservoir size after 48 weeks of treatment. Paradoxically, CCR5 blockade also induced a slower decrease in plasma viremia and immune activation.
感染早期产生的潜伏性HIV-1感染细胞是病毒持续存在的原因，我们推测在近期感染HIV-1的患者三联疗法中加用马拉维若可加速病毒储存库的衰减。
近期感染趋化因子受体5（CCR5）型HIV-1的患者被随机分为raltegravir+替诺福韦/恩曲他滨治疗方案组（对照组，n=15）或加用马拉维若强化的相同治疗方案组（+MVC组，n=15）。纵向检测血浆病毒载量、细胞相关HIV-1 DNA（总量、整合型和游离型）以及激活/炎症标志物。
两组血浆病毒载量均下降，在第48周时达到相似的残留水平。两组细胞相关HIV-1 DNA总量在第一个月也均下降，尽管随后+MVC组下降速度稍快。治疗开始后早期两组均观察到的两个长末端重复序列（2-LTR）环的短暂增加在接受马拉维若治疗的个体中下降更早。+MVC组早期（第12周）CD4 T细胞计数增加更高。相反，+MVC组CD8 T细胞计数和CD4 T细胞激活下降更慢。研究结束时两组的绝对CD4 T细胞和CD8 T细胞计数、免疫激活、CD4/CD8 T细胞比值以及可溶性炎症标志物相似。
在基于整合酶抑制剂的HIV-1感染早期治疗中加用马拉维若可更快减少2-LTR新感染细胞并使CD4 T细胞计数恢复，且治疗48周后病毒储存库总体大小有适度减少。矛盾的是，CCR5阻断也导致血浆病毒血症和免疫激活下降更慢。
