de Jong M D, Vella S, Carr A, Boucher C A, Imrie A, French M, Hoy J, Sorice S, Pauluzzi S, Chiodo F, Weverling G J, van der Ende M E, Frissen P J, Weigel H M, Kauffmann R H, Lange J M, Yoon R, Moroni M, Hoenderdos E, Leitz G, Cooper D A, Hall D, Reiss P
National AIDS Therapy Evaluation Centre, Department of Infectious Diseases, University of Amsterdam, Netherlands.
J Infect Dis. 1997 Apr;175(4):966-70. doi: 10.1086/514002.
High-dose nevirapine treatment has been reported to confer sustained antiretroviral effects, despite a rapid development of resistance. The use of this strategy was evaluated in 20 previously untreated human immunodeficiency virus type 1 (HIV-1) p24 antigenemic persons with CD4 cell counts between 100 and 500/mm3. Treatment consisted of 400 mg of nevirapine, after a 2-week lead-in dose of 200 mg. Rash was the most frequently reported adverse event, occurring in 25%. While sustained declines in p24 antigen levels were observed in the majority, serum HIV-1 RNA load and CD4 cell counts returned to baseline values within 12 weeks in virtually all subjects. The resistance-conferring tyrosine-to-cysteine substitution at reverse transcriptase position 181 was detected after 4 weeks in most subjects. These observations suggest that plasma drug levels attained with high-dose nevirapine were not sufficient to inhibit nevirapine-resistant virus, although they were approximately 2-fold higher than reported IC50 values of resistant virus.
据报道，高剂量奈韦拉平治疗可产生持续的抗逆转录病毒作用，尽管耐药性会迅速产生。在20名先前未经治疗、CD4细胞计数在100至500/mm³之间的1型人类免疫缺陷病毒（HIV-1）p24抗原血症患者中评估了该策略的使用情况。治疗方案为在2周导入剂量200mg奈韦拉平后，给予400mg奈韦拉平。皮疹是最常报告的不良事件，发生率为25%。虽然大多数患者的p24抗原水平持续下降，但几乎所有受试者的血清HIV-1 RNA载量和CD4细胞计数在12周内均恢复至基线值。大多数受试者在4周后检测到逆转录酶第181位密码子由酪氨酸突变为半胱氨酸，该突变可导致耐药。这些观察结果表明，高剂量奈韦拉平达到的血浆药物水平不足以抑制奈韦拉平耐药病毒，尽管该水平比已报道的耐药病毒IC50值高约2倍。
