Centre for Infectious Disease Epidemiology & Research, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa.
PLoS Med. 2012;9(9):e1001304. doi: 10.1371/journal.pmed.1001304. Epub 2012 Sep 4.
Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART.
Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population. Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22-1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12-1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86-1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located.
HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic. Please see later in the article for the Editors' Summary.
已证实接受抗逆转录病毒疗法（ART）的男性死亡率增加，但仍知之甚少。我们研究了 ART 治疗中性别差异导致死亡率的程度和危险因素。
分析纳入了 2002 年 1 月至 2009 年 12 月期间南非 8 个 ART 项目中开始接受 ART 的 46201 名 ART 初治成年人。从开始 ART 到出现结局或分析结束，对患者进行随访。主要结局是死亡率；次要结局是失访（LTF）、病毒学抑制和 CD4+细胞计数反应。生存分析用于检查性别对 ART 死亡风险的影响。敏感性分析仅限于病毒学抑制的患者和 CD4+细胞计数达到>200 个/μl 的患者。我们比较了 HIV 阳性患者在 ART 治疗中的死亡率与年龄标准化的 HIV 阴性人群中的死亡率。在 46201 名成年人（65%为女性，中位年龄 35 岁）中，在 77578 人年的随访期间，男性的 CD4+细胞计数中位数低于女性（85 与 110 个/μl，p<0.001），更有可能被归类为 WHO 分期 III/IV（86%与 77%，p<0.001），粗死亡率（8.5 与 5.7 例/100 人年，p<0.001）和调整分析（调整后的危险比 [AHR] 1.31，95%CI 1.22-1.41）更高。在开始 ART 后 36 个月，男性比女性更有可能真正失访（AHR 1.20，95%CI 1.12-1.28），但失访后死亡的可能性没有差异（AHR 1.04，95%CI 0.86-1.25）。所有八个项目均得出了一致的结果。性别之间病毒学抑制情况相似；女性的免疫反应略优于男性。值得注意的是，ART 治疗中的观察到的性别差异死亡率小于 HIV 阴性南非人群中年龄标准化死亡率的性别差异。随着时间的推移，非 HIV 死亡率似乎占观察到的死亡率的比例越来越大。该分析受到基线 HIV 疾病特征数据缺失的限制，并且我们没有观察到直接在参与队列所在的 HIV 阴性人群中的死亡率。
在南非的项目中，HIV 感染的男性在接受 ART 治疗后的死亡率高于女性，但这些差异仅部分归因于开始接受 ART 时 HIV 疾病更严重、失访和随后的死亡率以及对治疗的反应存在差异。ART 治疗中观察到的死亡率差异可能最好用南非人口中男性和女性之间与 HIV/AIDS 流行无关的背景死亡率差异来解释。请在文章后面查看编辑总结。
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