Geng Elvin H, Neilands Torsten B, Thièbaut Rodolphe, Bwana Mwebesa Bosco, Nash Denis, Moore Richard D, Wood Robin, Zannou Djimon Marcel, Althoff Keri N, Lim Poh Lian, Nachega Jean B, Easterbrook Philippa J, Kambugu Andrew, Little Francesca, Nakigozi Gertrude, Nakanjako Damalie, Kiggundu Valerian, Ki Li Patrick Chung, Bangsberg David R, Fox Matthew P, Prozesky HansW, Hunt Peter W, Davies Mary-Ann, Reynolds Steven J, Egger Matthias, Yiannoutsos Constantin T, Vittinghoff Eric V, Deeks Steven G, Martin Jeffrey N
Int J Epidemiol. 2015 Feb;44(1):251-63. doi: 10.1093/ije/dyu271.
Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally.
We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/ml in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years.
After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/ml was 529/ml [95% confidence interval (CI): 517–541] in North America, 494/ml (95% CI: 429–559) in West Africa, 515/ml (95% CI: 508–522) in Southern Africa, 503/ml (95% CI: 478–528) in Asia and 437/ml (95% CI: 425–449) in East Africa.
CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.
即使在接受抗逆转录病毒治疗后血浆HIV RNA复制得到完全抑制的HIV感染患者中，遗传因素（如CCL3L1拷贝数）、病毒因素（如嗜性）和环境因素（如长期暴露于微生物抗原）也会影响CD4细胞的恢复。这些因素在全球范围内差异显著，因此在HIV RNA受到抑制期间，预期的CD4细胞恢复情况在全球可能有所不同。
我们评估了来自北美、西非、东非、南非和亚洲的成年HIV感染者。这些患者开始接受基于非核苷类逆转录酶抑制剂的治疗方案，其中包含依非韦伦或奈韦拉平，在治疗的第一年中至少有一次HIV RNA水平<500/ml，并观察了HIV RNA受到抑制期间CD4细胞的变化。我们使用分段线性回归来估计居住地区对CD4细胞恢复的影响，并对社会人口统计学和临床特征进行了调整。我们在37825人年的时间里观察了来自105个队列的28217名患者。
调整后，与其他地区相比，东非患者的CD4细胞恢复有所减少。在开始抗逆转录病毒治疗三年后，一名治疗前CD4细胞计数为150/ml的典型患者的平均CD4细胞计数在北美为529/ml [95%置信区间（CI）：517–541]，在西非为494/ml（95% CI：429–559），在南非为515/ml（95% CI：508–522），在亚洲为503/ml（95% CI：478–528），在东非为437/ml（95% CI：425–449）。
与世界其他地区相比，东非在HIV RNA受到抑制期间CD4细胞的恢复有所减少，观察到的差异足够大，可能会影响临床结果。全球范围内的流行病学分析可以识别在临床、国家或个别地区层面无法观察到的宏观效应。
