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重回德班:站在终结艾滋病的开端
来源:中国科学报      作者:张章      时间:2016-08-01 00:00      关键词:科学家正在探索抗逆转录药物长期影响
摘要:16年前,一个11岁儿童遭遇了横扫南非的艾滋病流行。当时,瘦弱矮小的Nkosi Johnson代表南非艾滋病患者在该国举行的德班国际艾滋病大会上发言,恳请南非政府为携带艾滋病病毒(HIV)的孕妇提供azidothymidine(一种抗艾滋病药物),以防止孕妇将HIV传染给孩子。

“与艾共舞” 图片来源:Brent Stirton

16年前,一个11岁儿童遭遇了横扫南非的艾滋病流行。当时,瘦弱矮小的Nkosi Johnson代表南非艾滋病患者在该国举行的德班国际艾滋病大会上发言,恳请南非政府为携带艾滋病病毒(HIV)的孕妇提供azidothymidine(一种抗艾滋病药物),以防止孕妇将HIV传染给孩子。

“不要害怕我们,我们和普通人是一样的。”他对眼含泪水的听众说。Johnson从出生就携带HIV。但在之后的一周里,科学家、活动家和艾滋病否定论者之间发生了激烈争执。当时的南非总统Thabo Mbeki也否定了HIV是艾滋病的病因,一时激起公愤。

德班会议是全球防治艾滋病工作的分水岭。作为首个在发展中国家举行的国际艾滋病会议,它把全球目光聚焦到了南非这块病魔肆虐的土地上。在发达国家,抗逆转录病毒药物(ARV)给HIV染者带来了希望,但在贫困国家,艾滋病仍等于死刑,原因是治疗费用十分昂贵:每人每年的治疗费用超过1万美金。仅在该会议期间,大约有2500个南非人死于艾滋病,其中1/4是儿童。不到1年后,Johnson去世。

7月底,国际艾滋病大会又一次在德班举行,但这次情况完全改变了。政府内的艾滋病否定论者开始沉默,大量国际资金注入。如今,在南非700万名HIV感染者中,超过一半开始使用ARV——这是全球最大的抗艾项目。

2004年,南非平均人口寿命仅为53.4岁,而2015年,这一数字已达到62.5岁,这当中ARV的推广居功至伟。21世纪初,母婴HIV传播率高达30%,而现在下降至1.5%。“这简直是奇迹。”美国加州大学圣地亚哥分校全球卫生科学学院副院长、本次会议的主要演讲者之一的Steffanie Strathdee这样说道。

但巨大的挑战依然存在。南非仍是全球HIV感染率最高的国家,新发感染率居高不下,尤其是年轻女性。HIV感染率最高的是夸祖鲁-纳塔尔省,这里的一些小区,15岁的女孩一生中感染HIV的概率高达80%。因为这些感染非常难以追踪,所以流行病学家一直想弄清出现这种情况的原因。另外,大规模的ARV治疗计划对公共卫生系统产生了巨大压力,而且南非刚刚签署了一个扩展计划,把接受ARV治疗的人数扩大了一倍。

对于医生和医学研究人员而言,ARV带来了一个新问题:长期感染HIV和服用ARV对不同年龄患者健康的影响。部分研究者正在探索,当中老年患者服用了几十年ARV后,身体会出现哪些变化。其他科学家则试着弄清,如果胎儿在母体子宫内暴露于HIV或ARV,面临的健康风险,即便他们没有感染该病毒。

这些结果对世界其他地区也有重要意义,因为之后ARV会在全球范围内推广。联合国艾滋病规划署(UNAIDS)设立了一个名为90-90-90的目标:到2020年,90%的HIV感染者确诊其感染情况;90%的确诊阳性感染者获得ARV药物治疗;90%的ARV服用患者的病毒载量达到无法检测的水平。

可以说,南非是个试验场:查看ARV项目能否成功在发展中国家大规模展开,以及展开后能实现哪些效果。正如南非ARV项目中心主任Salim Abdool Karim 所说,“南非战胜艾滋病对全球消灭艾滋病非常关键。”

与艾共舞

年轻女孩Thembisa Mbhobho是南非抗艾明星。开普敦N2高速公路路口有她的大幅宣传画,上面的标语是“与HIV共舞”。 Mbhobho是南非数以百万计、每天服用ARV的患者之一。她指出,“如果你正确服药,多活50年不成问题。”

去年全球艾滋病日时,在无国界医生组织的支持下,当地艺术家需要绘制一幅宣传画进行艾滋病宣传,Mbhobho主动要求成为画中人。

26岁的Mbhobho表示,“2008年,我被确诊感染HIV,2014年开始服用ARV。”如今,她体内的HIV控制得非常好,血液测试甚至无法检出,大大降低了她传播HIV的风险。她希望人们能从她的宣传画或电视广告中得到勇气,从而更好地面对HIV。

南非推广ARV之路一直非常坎坷。它的第一个社区治疗计划于2001年开始,但由于HIV否定论者向政府提意见,很多HIV初期项目都只能被称为“可行性研究”。

国际医学界一直怀疑非洲能否有效地使用ARV进行治疗。2001年,美国国际开发署署长Andrew Natsios因为说,“很多非洲人一生都见不到一个钟或者手表,所以很难准时服药”,而备受指责。

事实证明他是错的。早期研究表明,在坚持用药和服药效果上,非洲患者比美国患者做得好。2004年,南非开始免费提供ARV,不到5万公民接受治疗。到了2007年,这个数字超过38万,而今天已然超过了300万。

但这个项目在南非和在欧洲和北美等发达地区的结果完全不同。南非无国界医生组织调解员Gilles van Cutsem指出,在欧洲,艾滋病病人不愿意接受ARV治疗。在南非,病人争相排队接受这种治疗。

不过,追踪ARV治疗非常具有挑战性。位于开普敦大学的南非国际流行病学艾滋病评估数据中心从2006年就开始追踪药物的发放。但该中心资深研究员和项目经理Morna Cornell表示,这些简单数据难以收集和解读。有时同一个人有多份记录,而且很多患者只有一些初期数据,后期数据都没有跟踪到。长期以来,该中心数据显示,艾滋病死亡的人数减少,而随访人数会不断减少。

Cornell指出,如果给病人设置特殊的标识符,那么追踪应该简单得多。她认为,更好的数据将帮助南非改善HIV项目,有助于今后的研究。许多科学家希望看到更详细的临床资料,以便研究长期服用ARV的副作用。

危险耐药性

耐药性是一个迫在眉睫的问题。在富裕国家,每个患者都会接受耐药性测试,确保药物对其有效。但是在南非,ARV是通过国家卫生系统免费发放的,耐药性测试几乎完全被忽略。英国维康信托资助非洲人口健康中心主任Deenan Pillay指出,“人们认为耐药性不是问题。但未来南非将出现耐ARV问题。你不能在没有测试的情况下,随便给大批人口用这些药。”

该中心拥有超过15年的纵向数据,这些数据来自夸祖鲁-纳塔尔省一个小区,该小区人口超过10万。数据显示,耐药性问题日益突出。2010年到2012年间,新发病例耐药比例增加了7%。Pillay认为,这个数字还会增加。“一旦这些药物组合失效,耐药的病人就根本无药可用了。这是很危险的。”

南非服用ARV的老年群体是另一个研究重点。未来30年里,50岁以上的HIV感染者占总数的比例将增加两倍。

一些研究已发现,服用ARV的患者发生某些肿瘤的概率更高,并且长期使用药物已被证实与高血压、糖尿病和肥胖风险增加有关——不过难以确定是药物还是HIV本身造成的。为了找到答案,研究人员正在寻找ARV对人体代谢的影响。虽然ARV的好处远超过这些潜在的副作用,但公共健康研究人员仍然急于知道ARV服用者到底会面临哪些问题。

伦敦卫生与热带医学院社会科学家Janet Seeley等人在研究乌干达和南非的50岁以上的病人时,惊讶地发现,服用ARV的HIV感染者生活质量比同龄HIV阴性者生活质量更高,日常活动更活跃。

她的第一念头是“这不可能”,但事实的确如此。不过研究者发现,在南非,相比于正常人组,接受HIV治疗的老年人更容易得其他慢性疾病。

另外,开普敦大学免疫学家Clive Gray正在调查子宫内HIV和ARV暴露对胎儿发育及对“暴露未感染”儿童的长期健康的影响。他和同事研究了尼日利亚和南非500对母婴——包括感染了HIV和未感染HIV的母亲。这项研究尚未完成,但Gray等人已经发现“暴露未感染”的儿童出生后第一年就出现免疫低下的问题。

打破恶性循环

但也许最紧迫的问题是ARV的大规模推广会对HIV的感染率有什么影响。低病毒载量的患者的传染力比较低,这促使世界卫生组织推荐HIV阳性者尽快使用ARV治疗,而不是等到CD4检测下降。今年5月,南非卫生部长Aaron Motsoaledi宣布,该国将从9月实施这些准则,把接收ARV治疗的患者人数增加一倍。 Motsoaledi还表示,卫生部将为感染率极高的性工作者提供预防性治疗。

即使小幅增加ARV覆盖率也能降低感染率。非洲中心的一项研究发现,有30%~40%的HIV感染者接受治疗的社区,新发HIV感染率会比小于10%的人接受治疗的低38%。

无论如何,这10多年里,南非抗艾滋病的战争取得了诸多成果。美国埃默里大学医学院全球健康研究者Carlos del Rio 表示,“多年前的德班会议让我们相信,没有什么是不可能的,现在南非的HIV感染者也能活下来了。”

但Rio认为,革命尚未成功。“我们面临的问题是,如果不能在这一代人里把HIV控制好,以后HIV更容易肆虐。”

人们已经处于艾滋病被终结的时代了吗?Rio认为,事实上,人们正处于终结艾滋病的开端。如果不继续投入资金,不继续把焦点放在HIV上,HIV仍会带来灾难性后果

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