The effect of highly active antiretroviral therapy on the survival of HIV-infected children in a resource-deprived setting: a cohort study.
The effect of highly active antiretroviral therapy on the survival of HIV-infected children in a resource-deprived setting: a cohort study.
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DOI：
10.1371/journal.pmed.1001044
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发表时间：
2011-06
期刊：
影响因子：
15.8
通讯作者：
Behets F
中科院分区：
文献类型：
--
作者：
Edmonds A;Yotebieng M;Lusiama J;Matumona Y;Kitetele F;Napravnik S;Cole SR;Van Rie A;Behets F
Andrew Edmonds 及其同事进行的这项观察性队列研究报告称，在资源匮乏的刚果民主共和国金沙萨，高效抗逆转录病毒疗法 (HAART) 显着提高了 HIV 感染儿童的生存率。高效抗逆转录病毒疗法（HAART）对艾滋病毒感染儿童生存的影响尚未得到很好的量化。由于大多数儿科艾滋病毒发生在低收入和中等收入国家，我们的目标是对生活在资源匮乏环境中的儿童的这种影响进行初步估计。对 2004 年 12 月至 2010 年 5 月期间在刚果民主共和国金沙萨参加艾滋病毒护理和治疗计划的未接受过 HAART 儿童的观察数据进行了分析。我们使用边际结构模型来估计HAART对生存的影响，同时考虑到受暴露影响的时间依赖性混杂因素。随访开始时，790 名儿童的中位年龄为 5.9 岁，其中 528 名（66.8%）患有晚期或严重免疫缺陷，405 名（51.3%）处于 HIV 临床 3 期或 4 期。这些儿童的观察时间中位数为 31.2 个月，总共贡献了 2,089.8 人年。 80 名儿童 (10.1%) 死亡，619 名 (78.4%) 名儿童开始接受 HAART，6 名 (0.8%) 名儿童转移至其他护理人员，76 名儿童 (9.6%) 失访。在接受HAART期间，死亡率为每100人年3.2人死亡（95%置信区间[CI] 2.4-4.2），在仅接受初级艾滋病毒护理期间，死亡率为每100人年6.0人死亡（95% CI 4.1-8.6）。根据边际结构模型，比较 HAART 与未进行 HAART 的死亡率风险比为 0.25（95% CI 0.06-0.95）。 HAART 将金沙萨艾滋病毒感染儿童的死亡风险降低了 75%，这一估计与据报道的 HAART 对美国儿童生存率的影响在数量上相似，但精确度较低。 请参阅本文后面的编辑摘要 2009 年，估计有 250 万儿童感染艾滋病毒，其中大多数（230 万）生活在撒哈拉以南非洲地区。这些儿童中的大多数（90%）是在怀孕、分娩或母乳喂养期间从感染艾滋病毒的母亲那里感染艾滋病毒的，这凸显了给予有效药物预防母婴传播的重要性。由于此类干预措施在大多数资源有限的国家（艾滋病毒负担最高）仍未广泛获得或可用，2009 年估计每天有 1,000 名儿童新感染艾滋病毒，但只有 360,000 名儿童正在接受高效抗逆转录病毒治疗 (HAART)。尽管HAART可以改善感染艾滋病毒的成年人的生存率，但人们对HAART对感染艾滋病毒的儿童的生存率的影响程度知之甚少——尽管已知不同年龄组对抗逆转录病毒治疗的反应有所不同。此外，由于儿童艾滋病毒的病程与成人不同（部分原因是病毒对未成熟胸腺的影响，这可能导致高HIV RNA病毒血症和快速死亡），因此将成人研究结果外推到儿童人群是不合适的。因此，必须专门量化 HAART 对儿童生存的影响。大多数关于治疗对儿童生存影响的观察性研究都是在意大利和美国等高收入国家进行的。由于大多数艾滋病毒感染儿童生活在资源匮乏地区，多种因素（例如延迟就诊和并发疾病发生率较高）可能对治疗结果产生不利影响，因此特别需要有关高效抗逆转录病毒治疗（HAART）对生活在低收入国家的艾滋病毒感染儿童的影响的信息。尽管在这些国家（例如科特迪瓦、海地、莱索托、泰国和赞比亚）的儿科队列中进行了一些调查，但 HAART 对资源匮乏环境中儿童死亡率的影响尚未准确量化。因此，在这项观察性临床队列研究中，研究人员调查了HAART对刚果民主共和国（DRC）金沙萨HIV感染儿童死亡率的影响。研究人员分析了 2004 年 12 月至 2010 年 5 月期间在刚果金沙萨参加 HIV 项目的 790 名儿童的数据，并使用统计模型（边际结构模型）来调整时间依赖性混杂因素，例如 HAART 通常在病情较重的患者（例如 CD4 细胞百分比较低的患者）中开始。假设所有开始HAART的儿童在整个随访过程中不间断地接受治疗，使用这个统计模型，研究人员能够比较所有儿童开始HAART与随访期间没有儿童开始HAART的死亡风险比。在这项研究中，790 名儿童中有 619 名 (78.4%) 在随访期间开始了 HAART，随访时间中位数为 31.2 个月，中位数为 30 次 HIV 护理就诊。在开始治疗的患者中，110 人 (17.8%) 由于不良事件或治疗失败而转而采用替代疗法。在 2,089.8 人年的累计随访期间，80 名儿童（10.1%）死亡，总死亡率为每 100 人年 3.8 人。比较HAART与未进行HAART的未经调整的死亡率比为0.54。研究人员利用边际结构模型估计，与不进行HAART相比，HAART将随访期间的死亡率风险（率）降低了75%。这些研究结果表明，HAART 治疗显着改善了刚果金沙萨感染 HIV 的儿童的生存率，并表明 HAART 在改善资源严重匮乏的国家（仍在从内战中恢复）的 HIV 感染儿童的生存率方面与在资源更加丰富的地区一样有效——鉴于绝大多数接受 HAART 的儿童生活在资源匮乏的地区，这是一个重要的发现。这项研究提供了更多证据，表明在资源匮乏国家加速向艾滋病毒感染儿童推广抗逆转录病毒疗法可以挽救生命且有效。未来的研究需要解决HAART在资源匮乏国家的受研究人群中的有效性，例如营养不良的儿童或患有结核病等合并感染的儿童。请通过此摘要的在线版本访问这些网站：http://dx.doi.org/10.1371/journal.pmed.1001044。世界卫生组织的网站提供了有关艾滋病毒感染儿童治疗的更多信息 无国界医生组织的基本药物获取运动网站提供了有关儿科高效抗逆转录病毒治疗的更多信息
This observational cohort study by Andrew Edmonds and colleagues reports that treatment with highly active antiretroviral therapy (HAART) markedly improves the survival of HIV-infected children in Kinshasa, DRC, a resource-deprived setting. The effect of highly active antiretroviral therapy (HAART) on the survival of HIV-infected children has not been well quantified. Because most pediatric HIV occurs in low- and middle-income countries, our objective was to provide a first estimate of this effect among children living in a resource-deprived setting. Observational data from HAART-naïve children enrolled into an HIV care and treatment program in Kinshasa, Democratic Republic of the Congo, between December 2004 and May 2010 were analyzed. We used marginal structural models to estimate the effect of HAART on survival while accounting for time-dependent confounders affected by exposure. At the start of follow-up, the median age of the 790 children was 5.9 y, 528 (66.8%) had advanced or severe immunodeficiency, and 405 (51.3%) were in HIV clinical stage 3 or 4. The children were observed for a median of 31.2 mo and contributed a total of 2,089.8 person-years. Eighty children (10.1%) died, 619 (78.4%) initiated HAART, six (0.8%) transferred to a different care provider, and 76 (9.6%) were lost to follow-up. The mortality rate was 3.2 deaths per 100 person-years (95% confidence interval [CI] 2.4–4.2) during receipt of HAART and 6.0 deaths per 100 person-years (95% CI 4.1–8.6) during receipt of primary HIV care only. The mortality hazard ratio comparing HAART with no HAART from a marginal structural model was 0.25 (95% CI 0.06–0.95). HAART reduced the hazard of mortality in HIV-infected children in Kinshasa by 75%, an estimate that is similar in magnitude but with lower precision than the reported effect of HAART on survival among children in the United States. Please see later in the article for the Editors' Summary In 2009, an estimated 2.5 million children were living with HIV, the majority of whom (2.3 million) were in sub-Saharan Africa. Most (90%) of these children acquired HIV from their HIV-infected mothers during pregnancy, birth, or breastfeeding, highlighting the importance of giving effective drugs for the prevention of mother to child transmission. As such interventions are still not widely accessible or available in most resource-limited countries, where the burden of HIV is highest, every day an estimated 1,000 children were newly infected with HIV in 2009, but only 360,000 children were receiving highly active antiretroviral therapy (HAART). Although HAART improves the survival of adults living with HIV, less is known about the degree to which HAART affects the survival of HIV-infected children—although response to antiretroviral treatment is known to differ across age groups. Furthermore, as the course of HIV disease in children is different from that in adults (partly because of the impact of the virus on the immature thymus, which can lead to high HIV RNA viremia and rapid death), it is inappropriate to extrapolate results from studies of adults to pediatric populations. Therefore, it is imperative that the effect of HAART on survival be quantified specifically in children. Most observational studies of the effects of treatment on child survival have been undertaken in high-income countries, such as Italy and the United States. As most children with HIV live in low-resource areas, where multiple factors, such as delayed presentation to care and a higher incidence of co-occurring conditions, might adversely affect treatment outcomes, there is a specific need for information on the effects of HAART in children with HIV living in low-income countries. Although some investigations have taken place in pediatric cohorts from such countries (for example, Côte d'Ivoire, Haiti, Lesotho, Thailand, and Zambia), the effect of HAART on mortality has not been accurately quantified among children in a resource-deprived setting. Therefore, in this observational clinical cohort study, the researchers investigated the effect of HAART on mortality in HIV-infected children in Kinshasa, in the Democratic Republic of the Congo (DRC). The researchers analyzed data from 790 children enrolled into an HIV program in Kinshasa, DRC, between December 2004 and May 2010 and used a statistical model (marginal structural models) to adjust for time-dependent confounding factors, such as the fact that HAART is typically initiated in sicker patients, for example, those with lower CD4 cell percentages. Assuming that all children starting HAART received it uninterruptedly throughout follow-up, using this statistical model, the researchers were able to compare the hazard ratio of death had all children initiated HAART to that had no children initiated HAART during follow-up. In the study, 619 out of the 790 children (78.4%) initiated HAART during follow-up and were followed for a median of 31.2 months, with a median of 30 HIV care visits. Of those who started treatment, 110 (17.8%) switched to an alternative regimen because of an adverse event or treatment failure. During the 2,089.8 accrued person-years of follow-up, 80 children (10.1%) died, giving an overall mortality rate of 3.8 deaths per 100 person-years. The unadjusted mortality rate ratio comparing HAART to no HAART was 0.54. Using a marginal structural model, the researchers estimated that compared to no HAART, HAART reduced the hazard (rate) of mortality during follow-up by 75%. These findings show that treatment with HAART markedly improved the survival of children infected with HIV in Kinshasa, DRC, and suggest that HAART is as effective in improving the survival of HIV-infected children in a severely resource-deprived country (still recovering from civil war) as in more resource-privileged settings—an important finding given that the vast majority of children receiving HAART live in resource-poor areas. This study provides additional evidence that accelerating rollout of antiretroviral therapy to children with HIV in resource-poor countries is lifesaving and effective. Future research needs to address how effective HAART is in understudied populations in resource-poor countries, such as undernourished children or those with co-infections such as tuberculosis. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001044. The World Health Organization's Web site has more information about the treatment of children living with HIV Médecins Sans Frontières's Campaign for Access to Essential Medicines Web site has more information on pediatric HAART
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影响因子：
4.8
作者：
Fewell, Zoe;Hernan, Miguel A.;Sterne, Jonathan A. C.
通讯作者：
Sterne, Jonathan A. C.
影响因子：
15.8
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)
通讯作者：
Swiss HIV Cohort Study (SHCS) and the International Epidemiologic Databases to Evaluate AIDS in Southern Africa (IeDEA-SA)
影响因子：
3.8
作者：
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通讯作者：
Msellati, P
DOI：
10.2471/blt.09.068015
发表时间：
2010-07-01
期刊：
Bulletin of the World Health Organization: International Journal of Public Health
影响因子：
--
作者：
Anaky, M-F;Duvignac, J;Leroy, V
通讯作者：
Leroy, V
影响因子：
7.7
作者：
Edmonds, Andrew;Lusiama, Jean;Behets, Frieda
通讯作者：
Behets, Frieda