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几内亚比绍与HIV-2相关的艾滋病及死亡率的长期随访:一项前瞻性开放队列研究。

Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau: a prospective open cohort study.

作者信息

Esbjörnsson Joakim, Månsson Fredrik, Kvist Anders, da Silva Zacarias J, Andersson Sören, Fenyö Eva Maria, Isberg Per-Erik, Biague Antonio J, Lindman Jacob, Palm Angelica A, Rowland-Jones Sarah L, Jansson Marianne, Medstrand Patrik, Norrgren Hans

机构信息

Department of Laboratory Medicine, Lund University, Malmö, Sweden; Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Department of Translational Medicine, Lund University, Malmö, Sweden.

出版信息

Lancet HIV. 2018 Nov 1. doi: 10.1016/S2352-3018(18)30254-6.

Abstract

BACKGROUND

HIV type 2 (HIV-2) is considered more benign and has fewer pathogenic consequences than HIV type 1 (HIV-1) for most infected individuals. However, reliable estimates of time to AIDS and mortality among those with HIV-2 infection are absent. We therefore aimed to compare the time to AIDS and mortality, and the CD4 T-cell dynamics between those infected with HIV-1 and HIV-2.

METHODS

We did a prospective open cohort study. We included all police officers with regular employment from police stations in both urban and rural areas of Guinea-Bissau since Feb 6, 1990. We continued to include participants until Sept 28, 2009, and follow-up of HIV-1-positive and HIV-2-positive individuals continued until Sept 28, 2013. We collected blood samples at enrolment and at scheduled annual follow-up visits at police stations. We analysed longitudinal data from individuals infected with HIV-1 and HIV-2 according to time to AIDS, time to death, and T-cell dynamics. Time of HIV infection was estimated as the mid-timepoint between last HIV-seronegative and first HIV-seropositive sample. Data from an additional 2984 HIV-uninfected individuals from the same population were analysed to assess the effect of natural mortality on HIV-related mortality.

FINDINGS

872 participants tested HIV positive during the 23-year study period: 408 were infected with HIV-1 (183 infected before and 225 infected after enrolment) and 464 were infected with HIV-2 (377 before and 87 after enrolment). The median time from HIV infection to development of AIDS was 6·2 years (95% CI 5·4-7·1) for HIV-1 infection and 14·3 years (10·7-18·0) for HIV-2 infection (p<0·0001). The median survival time after HIV infection was 8·2 years (95% CI 7·5-8·9) for HIV-1 infection and 15·6 years (12·0-19·2) for HIV-2 infection (p<0·0001). Individuals who were infected with HIV-1 or HIV-2 before enrolment showed similar results. Comparison with uninfected individuals indicated limited confounding contribution from natural mortality. Mean CD4 percentages were higher in individuals with HIV-2 than in those with HIV-1 during early infection (28·0% [SE 1·3] vs 22·3% [1·7]; p=0·00094) and declined at a slower rate (0·4% [0·2] vs 0·9% [0·2] per year; p=0·028). HIV-2-infected individuals developed clinical AIDS at higher mean CD4 percentages (18·2%, IQR 7·2-25·4) than HIV-1-infected individuals (8·2%, 3·0-13·8; p<0·0001).

INTERPRETATION

Our results show that both HIV-1-infected and HIV-2-infected individuals have a high probability of developing and dying from AIDS without antiretroviral treatment.

FUNDING

Swedish International Development Agency, Swedish Research Council, Swedish Society of Medical Research, Medical Faculty at Lund University, and Region Skåne Research and Development.

摘要

背景

对于大多数感染者而言,2型人类免疫缺陷病毒(HIV-2)被认为比1型人类免疫缺陷病毒(HIV-1)的致病性更低,导致的致病后果也更少。然而,目前尚缺乏对HIV-2感染者发生艾滋病及死亡时间的可靠估计。因此,我们旨在比较HIV-1感染者和HIV-2感染者发生艾滋病及死亡的时间,以及CD4 T细胞动力学情况。

方法

我们开展了一项前瞻性开放队列研究。自1990年2月6日起,我们纳入了几内亚比绍城乡两地警局所有在职的警察。我们持续纳入参与者直至2009年9月28日,并对HIV-1阳性和HIV-2阳性个体的随访持续至2013年9月28日。我们在入组时以及在警局定期进行的年度随访时采集血样。我们根据发生艾滋病的时间、死亡时间和T细胞动力学情况,对HIV-1感染者和HIV-2感染者的纵向数据进行分析。HIV感染时间估计为最后一次HIV血清阴性样本和首次HIV血清阳性样本之间的中点时间。我们还分析了来自同一人群的另外2984名未感染HIV个体的数据,以评估自然死亡率对HIV相关死亡率的影响。

结果

在为期23年的研究期间,872名参与者的HIV检测呈阳性:408人感染了HIV-1(183人在入组前感染,225人在入组后感染),464人感染了HIV-2(377人在入组前感染,87人在入组后感染)。HIV-1感染从感染到发展为艾滋病的中位时间为6.2年(95%CI 5.4 - 7.1),HIV-2感染为14.3年(10.7 - 18.0)(p<0.0001)。HIV-1感染从感染到死亡的中位生存时间为8.2年(95%CI 7.5 - 8.9),HIV-感染为15.6年(12.0 - 19.2)(p<0.0001)。入组前感染HIV-1或HIV-2的个体结果相似。与未感染个体的比较表明,自然死亡率的混杂作用有限。在早期感染期间,HIV-2感染者的平均CD4百分比高于HIV-1感染者(28.0%[SE 1.3]对22.3%[1.7];p = 0.00094),且下降速度较慢(每年0.4%[0.2]对0.9%[0.2];p = 0.028)。HIV-2感染者发生临床艾滋病时的平均CD4百分比(18.2%,IQR 7.2 - 25.4)高于HIV-1感染者(8.2%,3.0 - 13.8;p<0.0001)。

解读

我们的结果表明,在未接受抗逆转录病毒治疗的情况下,HIV-1感染者和HIV-2感染者都有很高的概率发展为艾滋病并死于艾滋病。

资助

瑞典国际开发署、瑞典研究理事会、瑞典医学研究协会、隆德大学医学院以及斯科讷地区研究与发展部门。

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