Institute for Global Health, University College London, London, United Kingdom.
Department of Infectious Disease, Imperial College London, London, United Kingdom.
PLoS One. 2021 Jul 21;16(7):e0253861. doi: 10.1371/journal.pone.0253861. eCollection 2021.
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.
研究血浆拉米夫定（3TC）、阿巴卡韦（ABC）、恩曲他滨（FTC）和替诺福韦（TFV）浓度与接受抗 HIV 治疗人群（PWH）认知功能的相关性。
从参加 POPPY 研究的接受 3TC/ABC 或 FTC/替诺福韦二吡呋酯（TDF）方案治疗的 PWH 中获得药代动力学（PK）和认知功能（Cogstate，六个领域）数据。使用秩回归调整潜在混杂因素，评估 PK 参数（AUC0-24：24 小时内浓度-时间曲线下面积、Cmax：最大浓度和 Ctrough：谷浓度）与认知评分（标准化为 z 分数）之间的相关性。
在 83 名接受 3TC/ABC 和 471 名接受 FTC/TDF 的 PWH 中，全球认知 z 评分中位数（IQR）分别为 0.14（-0.27，0.38）和 0.09（-0.28，0.42）。较高的 3TC AUC0-24 和 Ctrough 与更好的全球 z 评分相关[rho=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)]，独立于 ABC 浓度。在调整混杂因素和 3TC 浓度后，ABC PK 参数与全球和领域 z 评分的相关性均无统计学意义（所有 p 值均>0.05）。FTC 和 TFV PK 参数均与全球或领域认知评分无关。
虽然我们没有发现 ABC、FTC 和 TFV 血浆暴露对 PWH 认知功能的有害或有益影响，但较高的血浆 3TC 暴露通常与更好的认知表现相关，尽管较高的峰值浓度与较差的表现相关。
