Karris Maile Y, Jain Sonia, Day Tyler R C, Pérez-Santiago Josué, Goicoechea Miguel, Dubé Michael P, Sun Xiaoying, Spina Celsa, Daar Eric S, Haubrich Richard H, Morris Sheldon
a Department of Medicine , University California San Diego , San Diego , CA , USA.
b Department of Family and Preventive Medicine , University California San Diego , San Diego , CA , USA.
HIV Clin Trials. 2017 Mar;18(2):67-74. doi: 10.1080/15284336.2017.1282578. Epub 2017 Jan 30.
Nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens may potentially minimize antiretroviral (ART) toxicities, but demonstrate mixed efficacy and toxicity results. The impact of an integrase strand transfer inhibitor (INSTI) and protease inhibitor (PI) regimen on HIV viral dynamics and T cell kinetics remains underdescribed.
To compare the effect of raltegravir + ritonavir boosted lopinavir (RAL + LPV/r) to efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) on HIV kinetics and T cell dynamics.
Fifty participants naïve to ART underwent HIV viral kinetic sampling evaluated using biexponential mixed effects modeling. A subset of 28 subjects (with complete viral suppression) underwent flow cytometry and evaluation of soluble markers of inflammation at weeks 0, 4, and 48 of ART.
RAL + LPV/r compared to EFV/TDF/FTC resulted in a prolonged first phase viral decay rate (18 vs. 13 days p < 0.01). From weeks 0 to 4, RAL + LPV/r was associated with a trend toward greater decreases in activated CD4 T cells (-3.81 vs. -1.18 p = 0.09) and less decreases in activated effector memory CD4 T cells (-0.63 vs. -2.69 p-0.07). These trends did not persist to week 48. No differences were noted at any time point for soluble markers of immune activation.
The prolonged first phase viral decay observed with RAL + LPV/r in persons starting ART did not result in differences in viral suppression at week 48. We also observed trends in declines in certain cellular markers of immune activation but it remains unclear if this could translate to long-term immunologic benefits in persons on an INSTI + PI.
不含核苷类逆转录酶抑制剂(NRTI)的治疗方案可能会将抗逆转录病毒(ART)毒性降至最低,但疗效和毒性结果不一。整合酶链转移抑制剂(INSTI)和蛋白酶抑制剂(PI)方案对HIV病毒动力学和T细胞动力学的影响仍未得到充分描述。
比较拉替拉韦+利托那韦增强型洛匹那韦(RAL+LPV/r)与依非韦伦/替诺福韦酯/恩曲他滨(EFV/TDF/FTC)对HIV动力学和T细胞动力学的影响。
50名初治ART患者接受了HIV病毒动力学采样,采用双指数混合效应模型进行评估。28名受试者(病毒完全抑制)的亚组在ART治疗的第0、4和48周接受了流式细胞术检测和炎症可溶性标志物评估。
与EFV/TDF/FTC相比,RAL+LPV/r使病毒第一阶段衰减率延长(18天对13天,p<0.01)。从第0周到第4周,RAL+LPV/r与活化CD4 T细胞更大程度下降的趋势相关(-3.81对-1.18,p=0.09),而活化效应记忆CD4 T细胞下降较少(-0.63对-2.69,p=0.07)。这些趋势在第48周时未持续存在。免疫激活可溶性标志物在任何时间点均未观察到差异。
在开始ART治疗的患者中,RAL+LPV/r观察到的第一阶段病毒衰减延长在第48周时并未导致病毒抑制的差异。我们还观察到某些免疫激活细胞标志物下降的趋势,但尚不清楚这是否能转化为接受INSTI+PI治疗患者的长期免疫学益处。