title: Effect of antiretroviral therapy on hemoglobin A2 values can have implications in antenatal beta-thalassemia screening programs.
abstract: BACKGROUND
  Raised hemoglobin-A2 (HbA2) is the diagnostic hallmark of beta-thalassemia trait (βTT). Diagnostic difficulties may arise in HIV-positive patients on antiretroviral therapy (ART). We compared the effect of various antiretroviral drugs on HbA2 levels. We attempted to determine which drugs elevate HbA2 levels causing a false-positive diagnosis of βTT and correlate the findings with red cell indices.
  
  
  METHODS
  A retrospective analysis of the records of an antenatal thalassemia screening program was carried out for 78 HIV-positive adults (70 antenatal women and 8 husbands) to study the effect of antiretroviral drugs on HbA2 levels. Three had βTT; 20 treatment-naïve subjects constituted controls. The effects of zidovudine (36 cases), stavudine (7 cases), and tenofovir (12 cases) were evaluated. High-performance liquid chromatography was done for HbA2 levels. Values of 3.5-3.9% were borderline and ≥ 4% with hypochromic microcytosis was considered to be βTT.
  
  
  RESULTS
  Twenty individuals not on ART had normal HbA2%. Three patients had βTT and showed hypochromic microcytosis despite being on zidovudine. Fourteen of 55 patients on treatment (25.5%) had borderline HbA2 values (mean 3.7%): 11 were on a zidovudine-based regimen and 3 on a stavudine-based regimen. One patient on zidovudine had 4.1% HbA2 with normal Hb and severe macrocytosis (MCV 128.5 fl), leading to a false suspicion of βTT. All patients on tenofovir had normal HbA2. Hematological parameters, including mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and HbA2 levels were increased due to antiretroviral drugs zidovudine and stavudine.
  
  
  CONCLUSIONS
  Treatment-naïve subjects and those on tenofovir showed no effect on HbA2 levels compared with zidovudine and stavudine. A proportion of patients on zidovudine or stavudine had borderline elevated HbA2 levels, which could lead to a false impression of βTT.
authors.affiliation: a Department of Hematology , Postgraduate Institute of Medical Education and Research , Chandigarh , India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Bhagat
authors.affiliation: b Center of Excellence in HIV Care, Postgraduate Institute of Medical Education and Research , Chandigarh , India.|c Department of Internal Medicine , Postgraduate Institute of Medical Education and Research , Chandigarh , India.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Kaur Sachdeva
authors.affiliation: a Department of Hematology , Postgraduate Institute of Medical Education and Research , Chandigarh , India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Sharma
authors.affiliation: a Department of Hematology , Postgraduate Institute of Medical Education and Research , Chandigarh , India.
authors.forename: Man
authors.initials: M
authors.lastname: Updesh Singh Sachdeva
authors.affiliation: a Department of Hematology , Postgraduate Institute of Medical Education and Research , Chandigarh , India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Chhabra
authors.affiliation: b Center of Excellence in HIV Care, Postgraduate Institute of Medical Education and Research , Chandigarh , India.|c Department of Internal Medicine , Postgraduate Institute of Medical Education and Research , Chandigarh , India.
authors.forename: Aman
authors.initials: A
authors.lastname: Sharma
authors.affiliation: a Department of Hematology , Postgraduate Institute of Medical Education and Research , Chandigarh , India.
authors.forename: Reena
authors.initials: R
authors.lastname: Das
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D001774:Blood Chemical Analysis; D002851:Chromatography, High Pressure Liquid; D003955:Diagnostic Tests, Routine; D005189:False Positive Reactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006443:Hemoglobin A2 / Q000032:analysis*; D006801:Humans; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011296:Prenatal Diagnosis / Q000379:methods*; D012189:Retrospective Studies; D055815:Young Adult; D017086:beta-Thalassemia / Q000175:diagnosis*
chemical_list: D044966:Anti-Retroviral Agents; D006443:Hemoglobin A2
keywords: HIV; HbA2, antiretroviral treatment; stavudine; tenofovir; zidovudine