Effect of antiretroviral therapy on hemoglobin A2 values can have implications in antenatal beta-thalassemia screening programs

Background: Raised hemoglobin-A(2) (HbA(2)) is the diagnostic hallmark of beta-thalassemia trait (TT). Diagnostic difficulties may arise in HIV-positive patients on antiretroviral therapy (ART). We compared the effect of various antiretroviral drugs on HbA(2) levels. We attempted to determine which drugs elevate HbA(2) levels causing a false-positive diagnosis of TT 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 HbA(2) levels. Three had TT; 20 treatment-naive 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 HbA(2) levels. Values of 3.5-3.9% were borderline and4% with hypochromic microcytosis was considered to be TT. Results: Twenty individuals not on ART had normal HbA(2)%. Three patients had TT and showed hypochromic microcytosis despite being on zidovudine. Fourteen of 55 patients on treatment (25.5%) had borderline HbA(2) 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% HbA(2) with normal Hb and severe macrocytosis (MCV 128.5 fl), leading to a false suspicion of TT. All patients on tenofovir had normal HbA(2). Hematological parameters, including mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and HbA(2) levels were increased due to antiretroviral drugs zidovudine and stavudine. Conclusion: Treatment-naive subjects and those on tenofovir showed no effect on HbA(2) levels compared with zidovudine and stavudine. A proportion of patients on zidovudine or stavudine had borderline elevated HbA(2) levels, which could lead to a false impression of beta TT.