Muñoz de Benito Rosa María, Arribas López Jose Ramón
Hospital La Paz, Unidad de HIV, Paseo de La Castellana, 261, 28046 Madrid, Spain.
Expert Rev Anti Infect Ther. 2006 Aug;4(4):523-35. doi: 10.1586/14787210.4.4.523.
Truvada is the coformulation of tenofovir disoproxil fumarate (TDF; 300 mg) and emtricitabine (FTC; 200 mg) in a single tablet, providing the nucleotide backbone for once-daily dosing, as a component of highly active antiretroviral therapy (HAART). TDF (the bioavailable prodrug of tenofovir) is hydrolyzed to tenofovir intracellularly and phosphorylated to the active metabolite, tenofovir diphosphate. Tenofovir is a nucleotide analog of deoxyadenosine monophosphate, with activity against HIV-1, -2 and hepatitis B virus. FTC, the fluorinated derivative of lamivudine, is an analog of deoxycitidine, active against HIV-1, -2 and hepatitis B virus. Their long half-lives in plasma and in peripheral blood mononuclear cells allow once-daily dosing. Both are eliminated renally. Resistance mutation K65R is selected for by tenofovir and confers a two- to fourfold reduced susceptibility to this drug. The incidence of K65R is low (3%) and has not been observed in clinical trials with the concomitant use of tenofovir and FTC. FTC selects for M184V mutation less frequently than lamivudine. Tenofovir drug interactions include increased exposure to didanosine and inferior immune recovery that preclude their concomitant use. Boosted protease inhibitors increase exposure to tenofovir without dose adjustment required. FTC has no significant drug interactions. They are not metabolized by cytochrome P450, which confers little potential for interactions with drugs metabolized by these enzymes. As tenofovir and FTC are renally eliminated, drugs eliminated by tubular secretion must be avoided. Both antiretrovirals, as individual agents and in coadministration have evidenced antiviral potency in clinical trials. Pivotal study 934 evidenced superior efficacy of the combination TDF/FTC/efavirenz (EFV) versus zidovudine/FTC/EFV. The toxicity profile of tenofovir and FTC has been extensively studied. Lipid profile is more favorable with tenofovir than thymidine analog. Tenofovir requires surveillance of glomerular filtration rate and dosing interval adjustment when creatinine clearance is less than 50 ml/min and avoidance less than 30 ml/min. Fat loss is less likely with tenofovir than with thymidine analog. Clinical trials have assessed the performance of the coformulation of TDF and FTC.
特鲁瓦达是富马酸替诺福韦二吡呋酯（TDF；300毫克）和恩曲他滨（FTC；200毫克）的复方制剂，制成单片剂型，作为高效抗逆转录病毒疗法（HAART）的组成部分，提供每日一次给药的核苷酸骨架。TDF（替诺福韦的生物可利用前体药物）在细胞内水解为替诺福韦，并磷酸化为活性代谢物替诺福韦二磷酸。替诺福韦是脱氧腺苷单磷酸的核苷酸类似物，对HIV-1、-2和乙型肝炎病毒具有活性。FTC是拉米夫定的氟化衍生物，是脱氧胞苷的类似物，对HIV-1、-2和乙型肝炎病毒具有活性。它们在血浆和外周血单核细胞中的半衰期较长，允许每日一次给药。两者均经肾脏排泄。替诺福韦可选择耐药突变K65R，该突变使对该药物的敏感性降低2至4倍。K65R的发生率较低（3%），在替诺福韦与FTC联合使用的临床试验中未观察到。FTC选择M184V突变的频率低于拉米夫定。替诺福韦的药物相互作用包括与去羟肌苷的暴露增加以及免疫恢复较差，因此禁止两者同时使用。增强型蛋白酶抑制剂可增加替诺福韦的暴露，无需调整剂量。FTC没有显著的药物相互作用。它们不会被细胞色素P450代谢，因此与这些酶代谢的药物发生相互作用的可能性很小。由于替诺福韦和FTC经肾脏排泄，必须避免使用经肾小管分泌排泄的药物。这两种抗逆转录病毒药物作为单一药物以及联合使用在临床试验中均已证明具有抗病毒效力。关键研究934证明TDF/FTC/依非韦伦（EFV）组合相对于齐多夫定/FTC/EFV具有更高的疗效。替诺福韦和FTC的毒性特征已得到广泛研究。与胸苷类似物相比，替诺福韦对血脂的影响更有利。当肌酐清除率低于50毫升/分钟时，替诺福韦需要监测肾小球滤过率并调整给药间隔，当肌酐清除率低于30毫升/分钟时应避免使用。与胸苷类似物相比，替诺福韦导致脂肪流失的可能性较小。临床试验评估了TDF和FTC复方制剂的性能。
