Rajesh Radhakrishnan, Vidyasagar Sudha, Varma Danturulu Muralidhar, Mohiuddin Shabaz
Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.
Int J Risk Saf Med. 2011;23(3):171-80. doi: 10.3233/JRS-2011-0531.
In patients infected with human immunodeficiency virus (HIV), zidovudine has been known to cause a severe anemia that resolves promptly when the drug is stopped. The study was aimed to assess the incidence, the pattern of occurrence of zidovudine induced anemia, causality, severity, predictability, preventability and to identify risk factors for zidovudine induced anemia in Indian HIV positive patients in comparision with stavudine based highly active antiretroviral therapy (HAART).
This was a prospective observational study conducted over a period of 6 months by clinical pharmacists. Enrolled HIV positive patients were intensively monitored for zidovudine and stavudine induced anemia. zidovudine and stavudine fixed dose drug combinations of antiretroviral therapy (ART) were only included. The World Health Organization (WHO)/AIDS Clinical Trials Group (ACTG) definition of a severity grading of anemia was adopted. Each reported case of zidovudine and stavudine induced anemia was assessed for its causality by using the WHO probability scale and also with Naranjo's algorithm. Preventability was assessed using Schumock and Thornton criteria and severity was assessed using the modified Hartwig and Siegel scale. Multivariate logistic regression was used to evaluate the influence of zidovudine induced anemia. P-value < 0.05 was considered as statistically significant.
Monitoring of ninety eight HIV positive patients with fixed dose highly active antiretroviral therapy identified 19 cases of zidovudine induced anemia and 2 cases of stavudine induced anemia from 55 and 43 patients respectively. Incidence of zidovudine induced anemia in intensively monitored HIV positive patients was found to be 34.5%. Chi Square tests identified statistically significant incidence differences of anemia (p < 0.05) between the zidovudine group and the stavudine group. Grade 2 and grade 4 anemia accounted for 42.1%. Causality was 'probable' by WHO probability scale and 'definite' and 'probable' by Naranjo's algorithm. The Majority (89.4%) of zidovudine induced anemias were 'moderate' in severity. A total of 94.8% zidovudine induced anemias were probably preventable. Low baseline hemoglobin concentration less than 10.5 g/dl was observed as a risk factor for zidovudine induced anemia by multivariate logistic regression.
With the increasing access to zidovudine usage in India, clinicians must focus to avoid zidovudine based HAART regimens if baseline hemoglobin concentration is low, (i.e. less than 8 g/dl) thereby avoiding the occurrence of zidovudine induced anemia. Frequent monitoring of complete blood count (CBC) is important in patients on zidovudine therapy to prevent zidovudine induced anemia.
在感染人类免疫缺陷病毒（HIV）的患者中，已知齐多夫定可引起严重贫血，停药后贫血会迅速缓解。本研究旨在评估齐多夫定所致贫血的发生率、发生模式、因果关系、严重程度、可预测性、可预防性，并确定与基于司他夫定的高效抗逆转录病毒疗法（HAART）相比，印度HIV阳性患者中齐多夫定所致贫血的危险因素。
这是一项由临床药师进行的为期6个月的前瞻性观察研究。对纳入的HIV阳性患者进行密切监测，观察齐多夫定和司他夫定所致贫血情况。仅纳入抗逆转录病毒疗法（ART）的齐多夫定和司他夫定固定剂量药物组合。采用世界卫生组织（WHO）/艾滋病临床试验组（ACTG）的贫血严重程度分级定义。对每例报告的齐多夫定和司他夫定所致贫血病例，使用WHO概率量表和Naranjo算法评估其因果关系。使用Schumock和Thornton标准评估可预防性，使用改良的Hartwig和Siegel量表评估严重程度。采用多因素逻辑回归评估齐多夫定所致贫血的影响。P值<0.05被认为具有统计学意义。
对98例接受固定剂量高效抗逆转录病毒疗法的HIV阳性患者进行监测，分别从55例和43例患者中确定了19例齐多夫定所致贫血和2例司他夫定所致贫血。在密切监测的HIV阳性患者中，齐多夫定所致贫血的发生率为34.5%。卡方检验确定齐多夫定组和司他夫定组之间贫血的发生率存在统计学显著差异（p<0.05）。2级和4级贫血占42.1%。根据WHO概率量表，因果关系为“可能”，根据Naranjo算法，因果关系为“肯定”和“可能”。大多数（89.4%）齐多夫定所致贫血的严重程度为“中度”。总共94.8%的齐多夫定所致贫血可能是可预防的。多因素逻辑回归显示，基线血红蛋白浓度低于10.5 g/dl是齐多夫定所致贫血的危险因素。
随着印度齐多夫定使用的增加，如果基线血红蛋白浓度较低（即低于8 g/dl），临床医生必须注意避免使用基于齐多夫定的HAART方案，从而避免齐多夫定所致贫血的发生。对齐多夫定治疗的患者频繁监测全血细胞计数（CBC）对于预防齐多夫定所致贫血很重要。
