基于国产司他夫定和齐多夫定的抗HIV治疗优化方案的探索

Study of optimized regimens based on generic stavudine and zidovudine in antiretroviral therapy of HIV/AIDS patients

目的探索基于国产仿制高效抗反转录病毒治疗药物司他夫定(D4T)胶囊、齐多夫定(AZT)片为初始治疗方案的优化治疗策略,以达到良好的治疗效果,降低药物不良反应发生率,合理地使用国产仿制药物,最终能长期可持续的治疗。方法选择75例无机会性感染的、CD4+T淋巴细胞<350×106/L的、完成96周随访的艾滋病病毒(HIV)感染者/艾滋病(AIDS)患者,随机分为A组27例,服用D4T+拉米夫定(3TC)+奈韦拉平(NVP)/依非韦伦(EFV));B组27例,服用AZT+3TC+NVP/EFV;C组21例,前24周服用D4T+3TC+NVP/EFV,24周后服用AZT+3TC+NVP/EFV。观察3组的治疗效果及D4T、AZT的不良反应发生规律。结果治疗96周前后,A组患者的CD4+T淋巴细胞计数中位数分别是219(15～332)×106/L和420(203～635)×106/L,B组分别为224(28～332)×106/L和366(178～724)×106/L,C组分别为153(19～350)×106/L和411(95～728)×106/L。A、B、C 3组患者血浆HIV RNA<40拷贝/mL的比率分别为92.6%、96.3%、100%。A组D4T的不良反应发生率高达81.5%,主要发生在治疗36周之后;B组AZT的不良反应发生率高达48.2%,主要发生在治疗前12周内;C组在服用D4T24周后改服AZT,D4T的不良反应发生率为0,AZT的相关不良反应发生率为9.5%,明显低于A组(P<0.05)和B组(P<0.05)。结论 D4T治疗24周后更换为AZT的优化方案与长期服用D4T或AZT方案,均能获得满意的治疗效果,但不良反应发生概率优化方案明显低于长期D4T或AZT方案治疗者,可做为目前国产仿制药物初始治疗的优化方案。

Objective To identify an optimized highly active antiretroviral therapeutic（HAART） strategy based on domestically manufactured generic stavudine capsules（D4T） and zidovudine tablets（AZT） as reasonable initial regimens,in order to reduce the incidence of adverse reactions and enhance the therapeutic efficacy.Methods Seventy five HIV/AIDS subjects with CD＋4 cell count less than 350×106/L and without opportunistic infections who completed 96 week treatment were randomly assigned to Group A（27 subjects） receiving D4T＋3TC＋NVP/EFV and Group B（27 subjects） receiving AZT＋3TC＋NVP/EFV.and Group C（21 subjects） receiving D4T＋3TC＋NVP/EFV in the first 24 weeks and AZT＋3TC＋NVP/EFV in the second 24 weeks.The therapeutic efficacy and the incidence of adverse reactions due to D4T and AZT among the 3 groups were observed.Results The median CD＋4 counts in the 3 groups before and after the 96-week treatment in group A were 219（15-332）×106/L and 420（203-635）×106/L Group B were 224（28-332）×106/L and 366（178-724）×106/L in respectively;and those in Group C were 153（19-350）×106/L and 411（95-728）×106/L respectinely.The rates of plasma HIV RNA lower than 40 copies/mL were 92.6% in Group A,96.3% in Group B and 100% in Group C.The rate of adverse reactions related with D4T reached 81.48% in Group A,which mainly occurred after 36 weeks treatment;the rate of AZT related adverse reactions was 48.15% in Group B,which occurred in the first 12 weeks after beginning ART;and in Group C,D4T was changed to AZT after 24 weeks,then the rates of adverse reactions due to D4T was 0 and that due to AZT was 9.25%,obviously lower than in Group A（P0.05）and Group B（P0.05）.Conclusion The optimized HAART regimen using D4T for the first 24 weeks,and then switching to AZT showed the same satisfactory therapeutic efficacy as compared with the regimens based on D4T or AZT used for a long term,but the rate of adverse reactions in the former was obviously lower than in the latter.The optimized regimen can be recommended as an initial antiretroviral therapy based on domestically manufactured generic drugs.