Jevtović Dj, Ranin J, Salemović D, Brmbolić B, Zerjav S
Srp Arh Celok Lek. 1992 Nov;120 Suppl 5:38-41.
The unique nature of the replication cycle of the retroviruses, including HIV, offera number of possible targets for chemotherapeutic agents. These are RNA viruses which have the capacity to make DNA copies through their characteristic enzyme, reverse transcriptase, encoded in the pole region of the viral genoma. Reverse transcription is an attractive target for therapeutic intervention as this event is uniquelly associated with retroviruses. Dideoxynucleoside analogues can compete with endogenous nucleosides that are the natural substrate for reverse transcriptase or may be incorporated intro the growing chain of proviral DNA and terminate elongation. Reverse transcriptase inhibition is the principal mechanism of action of zidovudine (AZT) and related nucleosides, dideoxyinosine (ddl) and dideoxycitidine (ddC), which all attach to reverse transcriptase to the same site. This review will discuss current approaches to the antiretroviral therapy in AIDS patients. Several well controlled clinical trials have established both the efficacy and toxicity of AZT in patients with AIDS and severe ARC and it was shown that this drug decreased the incidence and severity of opportunistic infections, with the highly significant reduction in early mortality. The efficacy of newer reverse transcriptase-inhibiting nucleoside derivatives will be discussed too, as well as the issue of combination therapies.
包括人类免疫缺陷病毒(HIV)在内的逆转录病毒复制周期具有独特性质,这为化疗药物提供了多个可能的靶点。这些是RNA病毒,它们能够通过其特征性酶——逆转录酶,在病毒基因组的pol区域编码,来制造DNA拷贝。逆转录是治疗干预的一个有吸引力的靶点,因为这一过程与逆转录病毒独特相关。双脱氧核苷类似物可以与作为逆转录酶天然底物的内源性核苷竞争,或者可能被掺入前病毒DNA的生长链中并终止延伸。逆转录酶抑制是齐多夫定(AZT)及相关核苷(双脱氧肌苷(ddI)和双脱氧胞苷(ddC))的主要作用机制,它们都在同一位点与逆转录酶结合。本综述将讨论目前针对艾滋病患者的抗逆转录病毒治疗方法。多项严格对照的临床试验已经证实了AZT在艾滋病患者和严重艾滋病相关综合征(ARC)患者中的疗效和毒性,结果表明这种药物降低了机会性感染的发生率和严重程度,早期死亡率显著降低。还将讨论新型逆转录酶抑制核苷衍生物的疗效,以及联合治疗的问题。