抗人类免疫缺陷病毒1型化学治疗方案的新进展

Newest developments on therapeutic principles against HIV-1 infections

人类免疫缺陷病毒1型(HIV-1)感染者的CD4^+数目低于500×10~6个·L^(-1),应立即开始治疗。若CD4^+数目高于500×10~6个·L^(-1)可根据患者的综合病况作个性化处理,如患者病毒载量大于100 000拷贝·mL^(-1)、CD4^+细胞数目每年减低100×10~6个·L^(-1)以上,或是出现急性乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)合并感染以及有心血管疾病的危险和HIV-1相关的肾病症状也应迅速开始治疗。开始治疗方案常用依非韦伦(EFV)或由利托那韦激活(r)的另一个蛋白酶抑制剂加上2个核苷类逆转录酶抑制剂如替诺福韦酯(TDF)/恩曲他滨(FTC)或阿巴卡韦(ABC)/拉米夫定(3TC),但基本用药原则是因人而异。当发现治疗失败时应立即改换治疗,替代方案中,化疗药物至少应包括2～3个完全有效的药物,再加上一个作用于新靶点的药物,如雷特格韦,麦瑞韦若克或依曲韦林。随着高效抗逆转录病毒治疗的推广,急性的机会性感染率下降,而结核菌、HBV、HCV等慢性并发感染,非HIV-1相关的心血管疾病、肾疾病、骨骼疾病及脂质代谢障碍突显,因此认识和处理上述疾患是改善患者生存质量和延长患者生命的重要举措。齐多夫定(AZT)+3TC+洛匹那韦(LPV)/r、AZT/3TC/ABC被推荐用于HIV-1感染的妊娠妇女,可使婴儿感染HIV-1百分率降到1%以下。对HIV-1阳性的妊娠妇女及儿童应立即开始治疗,不管他们的病毒载量多高和CD4^+细胞数目多少。对那些职业HIV-1暴露者,特别是对于那些暴露于耐药病毒株的人员最好使用3药的治疗方案,如基于非核苷类逆转录酶抑制剂的EFV/(3TC或FTC)/(AZT或TDF);或基于蛋白酶抑制剂的LPV/r+(3TC或FTC)+AZT,而且力争在病毒暴露72 h内开始用药。

It is necessary to start therapy more than 500 CD4^＋ cells .μL-1, the initiating morbidities, including a high plasma virus load before CD4^＋ cell count drops below 500·μL-1. In patients with therapy should be individualized based on the presence of co （eg, 〉 100 000 copies·mL^-1）, a rapidly declining CD4^＋ cell count （〉 100./.IBL^-1 per year） , active hepatitis B or C co-infection, cardiovascular disease risk and HIV-1 associate nephropathy. The initiating regimen should be personalized, but the regimen usually includes EFV or a RTV-boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors （TDF/FTC or ABC/3TC） . Treatment failure should be identified and managed promptly, and the replacing regimen should include at least 2 - 3 fully active drugs plus a drug from a new class, such as RAL, MVC or TMC-125. With advances in antiretroviral therapy, acute opportunistic infections （OIs） have fallen dramatically, but chronic OIs such as tuberculosis, hepatitis B or C and non-AIDS-related events such as cardiovascular disease, renal disease, bone disease and lip dystrophy increase markedly. Managing and preventing these diseases are very important to the progress of HIV-1 infections. It is reported that the incidence of HIV infection in infants is decreased to less than 1% when HIV-l-infected women received antiretroviral therapy （AZT ＋ 3TC ＋ LPV/r, AZT/3TC/ABC）. HIV-l-infected children and pregnant women should start antiretroviral therapy despite their CD4^＋ cell number is high and viral load is low. The individuals who have the risk of occupational and non-occupational exposure to HIV-1 should use anti-HIV drugs （EFV/（3TC or FTC）/（AZT or TDF） or LPV/r ＋ （3TC or FTC） ＋ AZT within 72 hours after the exposure.