Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared.
Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared.
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DOI：
10.1371/journal.pmed.0050148
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发表时间：
2008-07-08
期刊：
影响因子：
15.8
通讯作者：
Swiss HIV Cohort Study (SHCS) and the International Epidemiologic Databases to Evaluate AIDS in Southern Africa (IeDEA-SA)
中科院分区：
文献类型：
--
作者：
Keiser O;Orrell C;Egger M;Wood R;Brinkhof MW;Furrer H;van Cutsem G;Ledergerber B;Boulle A;Swiss HIV Cohort Study (SHCS) and the International Epidemiologic Databases to Evaluate AIDS in Southern Africa (IeDEA-SA)
在资源有限的情况下提供高效抗逆转录病毒疗法遵循一种公共卫生方法，其特点是治疗方案数量有限，临床和实验室监测标准化。在工业化国家，医生根据现有的全部抗逆转录病毒药物开出处方，并辅以耐药性检测和频繁的实验室监测。我们比较了南非和瑞士开始HAART治疗的hiv感染患者的病毒学反应、一线治疗方案的改变和死亡率。我们分析了来自瑞士HIV队列研究和南非开普敦乡镇的两个HAART项目的数据。我们纳入了treatment-naïve年龄在16岁及以上且自2001年起开始使用至少三种药物治疗的患者，排除静脉注射吸毒者。研究人员分析了来自南非的2348名患者和来自瑞士HIV队列研究的1016名患者的数据。中位基线CD4+ T细胞计数在南非为80个细胞/μl，在瑞士为204个细胞/μl。在南非，患者开始使用四种一线方案中的一种，随后有514名患者（22%）改变了方案。在瑞士，最初使用了36种一线方案，539名患者（53%）改变了这些方案。在大多数患者中，HIV-1 RNA在一年内被抑制到500拷贝/ml或更低：96%（95%可信区间[CI] 95% - 97%）的南非患者和96%（94%-97%）的瑞士患者，分别有26%（22%-29%）和27%（24%-31%）的患者在两年内出现病毒反弹。在HAART治疗的头几个月，南非的死亡率高于瑞士：1-3个月的校正风险比为5.90 (95% CI 1.81-19.2)， 4-24个月的校正风险比为1.77（0.90-3.50）。与瑞士的高度个体化方法相比，南非的计划性HAART产生了相似的病毒学结果，初始方案的变化相对较少。南非需要进一步的创新和资源，以便更及时地获得HAART治疗，并改善开始HAART治疗的晚期疾病患者的预后。通过比较瑞士和南非的艾滋病毒治疗，Matthias Egger和他的同事发现，在两年多的时间里，病毒学结果是相似的。瑞士的药物选择是个体化的，而南非则采用了计划性的方法。自1981年第一例报告病例以来，获得性免疫缺陷综合症（艾滋病）已造成2 500多万人死亡，目前有3 000多万人感染了导致艾滋病的人类免疫缺陷病毒（艾滋病毒）。艾滋病毒破坏免疫系统细胞（包括CD4细胞，一种淋巴细胞），使感染者易受其他感染。在艾滋病流行初期，大多数艾滋病毒感染者在感染后10年内死亡。然后，在1996年，高效抗逆转录病毒疗法（HAART）——几种抗逆转录病毒药物的组合——被开发出来。现在，在资源丰富的国家，临床医生通过从20多种批准的药物中选择抗逆转录病毒药物的组合处方，为艾滋病毒感染者提供个性化的护理。发达国家治疗艾滋病毒的方法通常还包括经常监测患者血液中的病毒数量（病毒载量）、病毒耐药性测试（看是否有病毒对特定抗逆转录病毒药物具有耐药性）和定期CD4细胞计数（免疫系统健康的一种指标）。自从实施这些干预措施以来，这些国家的艾滋病毒感染者的健康和预期寿命大大改善。资源贫乏国家的艾滋病毒护理历史非常不同。最初，这些国家无力为其人口提供高效抗逆转录病毒治疗。然而，在2003年，各国政府、国际机构和供资机构开始实施在发展中国家增加HAART覆盖面的计划。截至2006年12月，低收入和中等收入国家急需治疗的艾滋病毒感染者中有四分之一以上正在接受HAART治疗。然而，发展中国家的HAART项目不是个体化治疗，而是遵循世界卫生组织制定的公共卫生方法。也就是说，药物方案、临床决策、临床和实验室监测都是标准化的。这种公共卫生方法考虑到卫生系统资源不足的现实，但它是否与个体化方法一样有效？研究人员通过比较南非（公共卫生方法）和瑞士（个体化方法）接受HAART治疗的患者的病毒学反应（治疗对病毒载量的影响）、一线（初始）治疗的变化和死亡率来解决这个问题。研究人员分析了自2001年以来收集的数据，这些数据来自南非开普敦两个乡镇（Gugulethu和Khayelitsha）参加HAART项目的2000多名患者，以及参加瑞士艾滋病毒队列研究的1000多名患者，这是一项针对艾滋病毒感染者的全国性研究。与瑞士的患者相比，南非的患者开始时CD4细胞计数较低，更有可能患上晚期艾滋病，他们开始接受四种一线治疗中的一种，在研究期间，大约四分之一的患者改用二线治疗。相比之下，瑞士使用了36种一线治疗方案，一半的患者改用了不同的治疗方案。尽管存在这些差异，但几乎所有患者的病毒载量在一年内都大大降低，两国四分之一的患者在两年内出现病毒反弹（低测量后病毒载量增加）。然而，南非的患者死亡率高于瑞士，特别是在治疗的前3个月。这些发现表明，就病毒学结果而言，南非采用的HAART公共卫生方法与瑞士采用的个体化方法同样有效。这是令人放心的，因为它表明可能导致病毒耐药性出现的“抗逆转录病毒无政府状态”（不受管制地使用抗逆转录病毒药物、中断药物供应和缺乏治疗监测）并没有像一些专家担心的那样在南非发生。因此，这些发现支持在资源贫乏的国家继续推行HAART的公共卫生方法。相反，他们还建议，在不损害其有效性的情况下，瑞士（和其他工业化国家）可以采取一种更加标准化的HAART方法。最后，南非的死亡率高于瑞士，这在一定程度上反映了南非的许多患者迫切需要HAART治疗，而且他们在治疗开始时病情较晚期，这表明南非和其他资源有限国家的艾滋病毒感染者将受益于及早开始治疗。请通过本摘要的在线版本http://dx.doi.org/10.1371/journal.pmed.0050148访问这些网站。世界卫生组织提供了关于普遍获得艾滋病毒治疗的信息（以几种语言提供），并提供了关于对艾滋病毒感染采取抗逆转录病毒治疗的公共卫生方法的建议。关于瑞士艾滋病毒队列研究以及在Gugulethu和Khayelitsha进行的研究的更多详细信息，可从美国国家过敏和传染病研究所获得关于艾滋病毒感染和艾滋病的信息艾滋病毒/艾滋病，包括有关抗逆转录病毒治疗的详细信息以及各国治疗指南的链接国际艾滋病慈善机构Avert提供有关世界各地艾滋病毒和艾滋病以及为数百万人提供艾滋病药物治疗的信息
The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/μl in South Africa and 204 cells/μl in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%–97%) in South Africa and 96% (94%–97%) in Switzerland, and 26% (22%–29%) and 27% (24%–31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81–19.2) during months 1–3 and 1.77 (0.90–3.50) during months 4–24. Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease. Comparing HIV treatment in Switzerland, where drug selection is individualized, and South Africa, where a programmatic approach is used, Matthias Egger and colleagues find similar virologic outcomes over two years. Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since the first reported case in 1981, and more than 30 million people are now infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of becoming infected. Then, in 1996, highly active antiretroviral therapy (HAART)—a combination of several antiretroviral drugs—was developed. Now, in resource-rich countries, clinicians provide individually tailored care for HIV-infected people by prescribing combinations of antiretroviral drugs chosen from more than 20 approved medicines. The approach to treatment of HIV in developed countries typically also includes frequent monitoring of the amount of virus in patients' blood (viral load), viral resistance testing (to see whether any viruses are resistant to specific antiretroviral drugs), and regular CD4 cell counts (an indication of immune-system health). Since the implementation of these interventions, the health and life expectancy of people with HIV has improved dramatically in these countries. The history of HIV care in resource-poor countries has been very different. Initially, these countries could not afford to provide HAART for their populations. In 2003, however, governments, international agencies, and funding bodies began to implement plans to increase HAART coverage in developing countries. By December 2006, more than a quarter of the HIV-infected people in low- and middle-income countries who urgently needed treatment were receiving HAART. However, instead of individualized treatment, HAART programs in developing countries follow a public-health approach developed by the World Health Organization. That is, drug regimens, clinical decision-making, and clinical and laboratory monitoring are all standardized. This public-health approach takes into account the realities of under-resourced health systems, but is it as effective as the individualized approach? The researchers addressed this question by comparing virologic responses (the effect of treatment on the viral load), changes to first-line (initial) therapy, and deaths in patients receiving HAART in South Africa (public-health approach) and in Switzerland (individualized approach). The researchers analyzed data collected since 2001 from more than 2,000 patients enrolled in HAART programs in two townships (Gugulethu and Khayelitsha) in Cape Town, South Africa, and from more than 1,000 patients enrolled in the Swiss HIV Cohort Study, a nationwide study of HIV-infected people. The patients in South Africa, who had a lower starting CD4 cell count and were more likely to have advanced AIDS than the patients in Switzerland, started their treatment for HIV infection with one of four first-line therapies, and about a quarter changed to a second-line therapy during the study. By contrast, 36 first-line regimens were used in Switzerland and half the patients changed to a different regimen. Despite these differences, the viral load was greatly reduced within a year in virtually all the patients and viral rebound (an increased viral load after a low measurement) developed within 2 years in a quarter of the patients in both countries. However, more patients died in South Africa than in Switzerland, particularly during the first 3 months of therapy. These findings suggest that the public-health approach to HAART practiced in South Africa is as effective in terms of virologic outcomes as the individualized approach practiced in Switzerland. This is reassuring because it suggests that “antiretroviral anarchy” (the unregulated use of antiretroviral drugs, interruptions in drug supplies, and the lack of treatment monitoring), which is likely to lead to the emergence of viral resistance, is not happening in South Africa as some experts feared it might. Thus, these findings support the continued rollout of the public-health approach to HAART in resource-poor countries. Conversely, they also suggest that a more standardized approach to HAART could be taken in Switzerland (and in other industrialized countries) without compromising its effectiveness. Finally, the higher mortality in South Africa than in Switzerland, which partly reflects the many patients in South Africa in desperate need of HAART and their more advanced disease at the start of therapy, suggests that HIV-infected patients in South Africa and in other resource-limited countries would benefit from earlier initiation of therapy. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050148. The World Health Organization provides information about universal access to HIV treatment (in several languages) and on its recommendations for a public-health approach to antiretroviral therapy for HIV infection More details on the Swiss HIV Cohort Study and on the studies in Gugulethu and Khayelitsha are available Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS HIV InSite has comprehensive information on all aspects of HIV/AIDS, including detailed information about antiretroviral therapy and links to treatment guidelines for various countries Information is available from Avert, an international AIDS charity, on HIV and AIDS around the world and on providing AIDS drug treatment for millions
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