Risk factors of treatment-limiting anemia after substitution of zidovudine for stavudine in HIV-infected adult patients on antiretroviral treatment

PLoS One. 2013;8(3):e60206. doi: 10.1371/journal.pone.0060206. Epub 2013 Mar 26.

Abstract

Background: Anemia is the main concern among patients using a zidovudine (AZT)-based antiretroviral treatment (ART). Some studies suggested weight-adjusted AZT dosing as a way to reduce toxicity. We analyzed the risk factors associated with AZT-induced anemia in a cohort using AZT as substitution for stavudine (D4T).

Methods: We retrospectively studied HIV-infected patients in a referral hospital in Phnom Penh, Cambodia between 2003 and 2011. Factors associated with AZT-related anemia requiring AZT-discontinuation within the first year after AZT initiation were analyzed using Cox regression.

Results: Overall, 1180 patients, 60.5% female, were included. At AZT initiation, the median hemoglobin was 12.7 g/dL (IQR 11.7-13.9), the median weight: 51 kg (IQR 45-58) and the median time on ART prior to AZT substitution: 1.4 years (IQR 1.0-2.0). Within one year follow-up, 139 patients (11.8%) developed anemia requiring AZT discontinuation. Overall, there was no independent association of body weight with AZT discontinuation. AZT discontinuation was associated with lower hemoglobin level when starting AZT; older age and taking D4T-based ART less than one year prior to AZT. In exploratory analysis, a linear increase in risk of grade 2-4 anemia with lower body weight was seen if starting AZT substitution within less than one year of D4T-based ART.

Conclusion: Our findings argue against the need of weight-based dosing of AZT to reduce anemia among patients using AZT as substitution for D4T. Whether this also applies to ART-naïve individuals remains to be assessed. Future studies with AZT dose reduction should assess efficacy and overall tolerance of AZT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anemia / chemically induced*
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use*
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Retrospective Studies
  • Risk Factors
  • Stavudine / adverse effects
  • Stavudine / therapeutic use*
  • Zidovudine / adverse effects*
  • Zidovudine / therapeutic use*

Substances

  • Anti-HIV Agents
  • Zidovudine
  • Stavudine

Grants and funding

The HIV program was supported by the Belgian Directorate General of Development Cooperation through the framework agreement with the Institute of Tropical Medicine, Antwerp, the Global Fund to fight AIDS, Tuberculosis and Malaria, and Hope World Wide. JvG is supported by the InBev-Baillet Latour Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.