Evaluation of incidence of zidovudine induced anemia in Indian human immunodeficiency virus positive patients in comparison with stavudine based highly active antiretroviral therapy.

Objectives: 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).

Methods: 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.

Results: 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.

Conclusion: 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.