Prins M, Brettle R P, Robertson J R, Hernández Aguado I, Broers B, Carré N, Goldberg D J, Zangerle R, Coutinho R A, van den Hoek A
Municipal Health Service, Division of Public Health and Environment, Amsterdam, The Netherlands.
Int J Epidemiol. 1999 Jun;28(3):541-9. doi: 10.1093/ije/28.3.541.
Human immunodeficiency virus (HIV) disease progression might vary by geographical region due to differences in the spectrum of HIV-related illnesses and (access to) health care. Therefore, the effect of geographical region, next to the effect of other potential cofactors, on disease progression in 664 injecting drug users (IDU) with documented HIV seroconversion from eight cohorts in Europe was studied.
Kaplan-Meier methods and Cox proportional hazards analysis were performed to assess the effect of geographical region, other sociodemographics, drug use and repeated HIV exposure on progression from HIV seroconversion to immunosuppression, AIDS and death with AIDS. We considered the confounding effect of study-design related factors (e.g. setting of follow-up), and accounted for pre-AIDS death from natural causes by imputing when each endpoint would have occurred, had they not died without AIDS.
Estimates of progression to AIDS and death with AIDS were substantially faster after taking pre-AIDS mortality into account. Median incubation time from seroconversion to the first CD4 count < 200 cells/microliter was 7.7 years (95% CI: 7.1-8.3) and to AIDS 10.4 years (95% CI: 9.8-infinity). The 10-year survival was 70.3% (95% CI: 62.8-76.6). The relative hazards (RH) of AIDS for IDU from central and southern Europe compared with IDU from northern Europe was 1.9 (95% CI: 1.2-3.0) and 1.2 (95% CI: 0.6-2.3), respectively, before, and 1.5 (95% CI: 0.7-3.2) and 1.1 (95% CI: 0.6-2.3) after taking differences in study-design related factors into account. Accounting for these factors, the RH of death with AIDS was 0.9 (95% CI: 0.3-2.5) for central and 1.2 (95% CI: 0.4-3.4) for southern Europe compared with northern Europe. For the first CD4 count < 200 cells/microliter these figures were 0.8 (95% CI: 0.5-1.4) and 0.8 (95% CI: 0.5-1.4). Age at seroconversion was the strongest predictor of disease progression. No statistically significant differences in disease progression were found by gender, foreign nationality, drug use and potential repeated HIV exposure.
We found no evidence for regional variability in HIV disease progression among European IDU. Future studies evaluating geographical differences should consider the confounding effect of study-design related factors and differential non-AIDS mortality. As age is an important determinant of disease progression, it should be considered in recommending treatment.
由于与艾滋病相关疾病谱及医疗保健(可及性)的差异,人类免疫缺陷病毒(HIV)疾病进展可能因地理区域而异。因此,除其他潜在辅助因素的影响外,还研究了地理区域对来自欧洲八个队列的664名有记录HIV血清转化的注射吸毒者(IDU)疾病进展的影响。
采用Kaplan-Meier方法和Cox比例风险分析,以评估地理区域、其他社会人口统计学因素、药物使用及反复HIV暴露对从HIV血清转化到免疫抑制、获得性免疫缺陷综合征(AIDS)及AIDS相关死亡进展的影响。我们考虑了研究设计相关因素(如随访环境)的混杂效应,并通过推算如果他们没有死于非AIDS原因时每个终点会在何时发生,来计入自然原因导致的AIDS前期死亡。
计入AIDS前期死亡率后,进展至AIDS及AIDS相关死亡的估计值大幅加快。从血清转化到首次CD4细胞计数<200个/微升的中位潜伏期为7.7年(95%可信区间:7.1 - 8.3),到AIDS为10.4年(95%可信区间:9.8 - ∞)。10年生存率为70.3%(95%可信区间:62.8 - 76.6)。与来自北欧的IDU相比,来自中欧和南欧的IDU发生AIDS的相对风险(RH)在考虑研究设计相关因素差异之前分别为1.9(95%可信区间:1.2 - 3.0)和1.2(95%可信区间:0.6 - 2.3),考虑这些因素之后分别为1.5(95%可信区间:0.7 - 3.2)和1.1(95%可信区间:0.6 - 2.3)。考虑这些因素后,与北欧相比,中欧AIDS相关死亡的RH为0.9(95%可信区间:0.3 - 2.5),南欧为1.2(95%可信区间:0.4 - 3.4)。对于首次CD4细胞计数<200个/微升,这些数字分别为0.8(95%可信区间:0.5 - 1.4)和0.8(95%可信区间:0.5 - 1.4)。血清转化时的年龄是疾病进展的最强预测因素。在疾病进展方面,未发现性别、外国国籍、药物使用及潜在反复HIV暴露有统计学显著差异。
我们未发现欧洲IDU中HIV疾病进展存在区域差异的证据。未来评估地理差异的研究应考虑研究设计相关因素的混杂效应及不同的非AIDS死亡率。由于年龄是疾病进展的重要决定因素,在推荐治疗时应予以考虑。