Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in people with HIV.

To investigate the associations of plasma lamivudine (3TC), abacavir (ABC), emtricitabine (FTC) and tenofovir (TFV) concentrations with cognitive function in a cohort of treated people with HIV (PWH). Pharmacokinetics (PK) and cognitive function (Cogstate, six domains) data were obtained from PWH recruited in the POPPY study on either 3TC/ABC or FTC/tenofovir disoproxil fumarate (TDF)-containing regimens. Association between PK parameters (AUC0-24: area under the concentration-time curve over 24 hours, Cmax: maximum concentration and Ctrough: trough concentration) and cognitive scores (standardized into z-scores) were evaluated using rank regression adjusting for potential confounders. Median (IQR) global cognitive z-scores in the 83 PWH on 3TC/ABC and 471 PWH on FTC/TDF were 0.14 (-0.27, 0.38) and 0.09 (-0.28, 0.42), respectively. Higher 3TC AUC0-24 and Ctrough were associated with better global z-scores [rho = 0.29 (p = 0.02) and 0.27 (p = 0.04), respectively], whereas higher 3TC Cmax was associated with poorer z-scores [rho = -0.31 (p<0.01)], independently of ABC concentrations. Associations of ABC PK parameters with global and domain z-scores were non-significant after adjustment for confounders and 3TC concentrations (all p’s>0.05). None of the FTC and TFV PK parameters were associated with global or domain cognitive scores. Whilst we found no evidence of either detrimental or beneficial effects of ABC, FTC and TFV plasma exposure on cognitive function of PWH, higher plasma 3TC exposures were generally associated with better cognitive performance although higher peak concentrations were associated with poorer performance.

在一组接受治疗的艾滋病病毒感染者（PWH）中研究拉米夫定（3TC）、阿巴卡韦（ABC）、恩曲他滨（FTC）和替诺福韦（TFV）的血浆浓度与认知功能的关联。 从POPPY研究中招募的使用含3TC/ABC或FTC/富马酸替诺福韦二吡呋酯（TDF）方案的艾滋病病毒感染者获取药代动力学（PK）和认知功能（Cogstate，六个领域）数据。使用秩回归并对潜在混杂因素进行调整，评估药代动力学参数（AUC0 - 24：24小时浓度 - 时间曲线下面积，Cmax：最大浓度，Ctrough：谷浓度）与认知评分（标准化为z评分）之间的关联。 83名使用3TC/ABC的艾滋病病毒感染者和471名使用FTC/TDF的艾滋病病毒感染者的总体认知z评分中位数（四分位间距）分别为0.14（-0.27，0.38）和0.09（-0.28，0.42）。较高的3TC AUC0 - 24和Ctrough与较好的总体z评分相关[rho分别为0.29（p = 0.02）和0.27（p = 0.04）]，而较高的3TC Cmax与较差的z评分相关[rho = -0.31（p<0.01）]，且与ABC浓度无关。在对混杂因素和3TC浓度进行调整后，ABC药代动力学参数与总体和领域z评分的关联无统计学意义（所有p>0.05）。FTC和TFV的药代动力学参数均与总体或领域认知评分无关。 虽然我们没有发现ABC、FTC和TFV的血浆暴露对艾滋病病毒感染者的认知功能有有害或有益影响的证据，但较高的血浆3TC暴露通常与较好的认知表现相关，尽管较高的峰值浓度与较差的表现相关。