De Clercq E
Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10 - B 3000 Leuven.
Verh K Acad Geneeskd Belg. 2007;69(2):65-80.
Of the 38.6 million people living with HIV/AIDS globally, almost 25 million (65%) live in sub-Saharan Africa. Preventive strategies and measures fall short, often simply because they are not available or are largely male-controlled. A preventive HIV vaccine is still far away; hence the drive to develop alternative prevention technologies, such as microbicides and oral pre-exposure prophylaxis, that could be female controlled. There are, at present, twenty-two anti-HIV drugs which have been formally licensed for clinical use in the treatment of HIV infections (AIDS): zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir, nevirapine, delavirdine, efavirenz, saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir, darunavir and enfuvirtide. These compounds, in combination, form the basis of HAART (highly active antiretroviral therapy), which has led to the development of a single daily pill existing of the combination of tenofovir disoproxil fumarate, emtricitabine and efavirenz, which has to be taken orally once daily for the treatment of AIDS. Beyond development of new drugs and clinical evaluation of existing medications, several companies within the pharmaceutical industry have established innovative policies that provide HIV medications at affordable prices in the least-developed countries. Reduced pricing is not alone a solution, and thus companies are actively working in partnership with the World Health Organization and other multinational groups to address roadblocks such as complex registration and procurement systems. Even in this period of successful anti-HIV therapy via HAART, a growing number of patients is cycling through the various remaining therapeutic options and are increasingly becoming dependent of the availability of newly developed anti-HIV agents. It is of concern that existing and future therapies will have to be effective against newly evolving (including drug-resistant) HIV variants in patients who currently face many years, if not decades, of chronic anti-HIV drug treatment. In spite of continuous long-term interventions to promote safer sexual behaviour, HIV prevalence is high and still rising in many parts of the world. The face of the epidemic is now black, female, young and poor..., and female controlled methods are urgently needed. Female controlled methods such as microbicides and cervical barrier methods provide hopeful perspectives when condom use is low due to social, cultural and/or economic factors, but, after all, the oral administration of a single daily pill would seem the most convenient way to prevent HIV infection, as its protective activity may be independent of the route of viral transmission.
全球3860万艾滋病毒/艾滋病感染者中,近2500万(65%)生活在撒哈拉以南非洲。预防策略和措施往往效果不佳,原因很简单,要么是无法获得这些策略和措施,要么主要由男性掌控。预防性艾滋病毒疫苗仍遥遥无期;因此人们努力研发其他预防技术,如杀菌剂和口服暴露前预防药物,这些可以由女性掌控。目前,有22种抗艾滋病毒药物已正式获得临床使用许可,用于治疗艾滋病毒感染(艾滋病):齐多夫定、去羟肌苷、扎西他滨、司他夫定、拉米夫定、阿巴卡韦、恩曲他滨、替诺福韦、奈韦拉平、地拉韦啶、依非韦伦、沙奎那韦、利托那韦、茚地那韦、奈非那韦、安普那韦、洛匹那韦、阿扎那韦、福沙那韦、替拉那韦、达芦那韦和恩夫韦肽。这些化合物联合使用构成了高效抗逆转录病毒疗法(HAART)的基础,该疗法促成了一种每日服用一次的单片复方制剂的研发,其成分是富马酸替诺福韦二吡呋酯、恩曲他滨和依非韦伦,用于治疗艾滋病时需每日口服一次。除了研发新药和对现有药物进行临床评估外,制药行业的几家公司制定了创新政策,以实惠的价格在最不发达国家提供艾滋病毒药物。降价并非唯一的解决办法,因此各公司正积极与世界卫生组织及其他跨国组织合作,以解决复杂的注册和采购系统等障碍。即便在通过HAART成功进行抗艾滋病毒治疗的现阶段,越来越多的患者在尝试各种剩余的治疗方案,并且越来越依赖新研发的抗艾滋病毒药物的供应。令人担忧的是,对于目前面临多年甚至数十年长期抗艾滋病毒药物治疗 的患者而言,现有及未来的疗法必须能有效对抗新出现的(包括耐药的)艾滋病毒变种。尽管持续进行长期干预以促进更安全的性行为,但在世界许多地区,艾滋病毒感染率依然很高且仍在上升。如今这一流行病的面貌是黑人、女性、年轻人和穷人……,因此迫切需要由女性掌控的方法。当由于社会、文化和/或经济因素导致避孕套使用率较低时,杀菌剂和子宫颈屏障方法等由女性掌控的方法提供了充满希望的前景,不过,每日口服一片药似乎是预防艾滋病毒感染最便捷的方式,因为其保护作用可能与病毒传播途径无关。