aHIV Epidemiology and Biostatistics group, Research Department of Infection and Population Health, University College London, London, UK bHospital Clinic i Provincial, Barcelona, Spain cCentrum Diagnostyki i Terapii AIDS, Warsaw, Poland dUniversity Hospital Zürich, University of Zurich, Zurich, Switzerland eWest-Tallinn Central Hospital, Tallinn, Estonia fThe Belgrade University School of Medicine Hospital for Infectious and Tropical Diseases, Belgrade, Serbia gHospital Curry Cabral, Lisbon, Portugal hCopenhagen HIV Program, University of Copenhagen iDepartment of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark. *Members of the steering committee are shown in appendix.
AIDS. 2013 Mar 27;27(6):907-918. doi: 10.1097/QAD.0b013e32835cb766.
CD4 cell count and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or increase the risk of disease this would not be identified prior to licensing. The aim of this study was to investigate the CD4 cell count and viral load-specific rates of fatal and nonfatal AIDS and non-AIDS events according to current antiretrovirals.
Poisson regression was used to compare overall events (fatal or nonfatal AIDS, non-AIDS or death), AIDS events (fatal and nonfatal) or non-AIDS events (fatal or nonfatal) for specific nucleoside pairs and third drugs used with more than 1000 person-years of follow-up (PYFU) after 1 January 2001.
Nine thousand, eight hundred and one patients contributed 42372.5 PYFU, during which 1203 (437 AIDS and 766 non-AIDS) events occurred. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global P-value = 0.084), and third drugs (global P-value = 0.031). As compared to zidovudine/lamivudine, patients taking abacavir/lamivudine [adjusted incidence rate ratio (aIRR) 1.22; 95% CI 0.99-1.49] and abacavir and one other nucleoside [aIRR 1.51; 95% CI 1.14-2.02] had an increased incidence of overall events. Comparing the third drugs, those taking unboosted atazanavir had an increased incidence of overall events compared with those taking efavirenz (aIRR 1.46; 95% CI 1.09-1.95).
There was little evidence of substantial differences between antiretrovirals in the incidence of clinical disease for a given CD4 cell count or viral load, suggesting there are unlikely to be major unidentified adverse effects of specific antiretrovirals.
CD4 细胞计数和病毒载量被用于临床试验中，作为评估新的抗逆转录病毒药物疗效的替代终点。如果抗逆转录病毒药物通过其他途径起作用或增加疾病风险，那么在获得许可之前是无法发现的。本研究旨在根据目前的抗逆转录病毒药物，研究 CD4 细胞计数和病毒载量特异性的致命和非致命艾滋病及非艾滋病事件的发生率。
采用泊松回归比较了 2001 年 1 月 1 日后随访超过 1000 人年（人年），有超过 1000 人年（人年）随访的特定核苷对和第三类药物的总事件（致命或非致命艾滋病、非艾滋病或死亡）、艾滋病事件（致命和非致命）或非艾滋病事件（致命或非致命）。
9810 名患者共提供了 42372.5 人年的随访数据，期间发生了 1203 例（437 例艾滋病和 766 例非艾滋病）事件。调整后，核苷对（全局 P 值=0.084）和第三类药物（全局 P 值=0.031）之间的总事件发生率存在弱证据差异。与齐多夫定/拉米夫定相比，使用阿巴卡韦/拉米夫定（调整后的发病率比[aIRR]1.22；95%CI 0.99-1.49）和阿巴卡韦和另一种核苷（aIRR 1.51；95%CI 1.14-2.02）的患者发生总事件的风险增加。在比较第三类药物时，与使用依非韦伦相比，未增强的阿扎那韦的患者总事件发生率增加（aIRR 1.46；95%CI 1.09-1.95）。
在给定的 CD4 细胞计数或病毒载量下，不同抗逆转录病毒药物的临床疾病发生率几乎没有明显差异，这表明不太可能存在特定抗逆转录病毒药物的重大未识别不良反应。
