Objective. To assess the level of haemoglobin A2 in HIV patients on antiretroviral therapy (ART) including zidovudine with untreated HIV patients. Material and Methods. The study was a case control study. A total of 185 patients were included in the study; the case group included 125 HIV patients who were on antiretroviral therapy (ART) including zidovudine and 60 were in the control group who were not receiving ART. The high-performance liquid chromatography (HPLC) was done and hemoglobin A2 level was observed; value more than 3.5% was considered significant. The Hb A2 percentages of HIV patients were compared with those of control using an unpaired t-test. Results. The mean of Hb A2 in case group was 3.462% (SD 0.675) and in control group it was 2.815% (SD0.246). The higher Hb A2 value was seen in significant number of treated patients than control group ( ). Conclusion. The clinicians, pathologists, haematologists, and genetic counsellors should be aware of effects of nutritional anaemia and ART on Hb A2 to reduce the chances of misdiagnosis of β-thalassaemia especially in developing countries and for centres for antenatal screening. 1. Introduction Cooley and Lee were the first to describe the diminished rate of synthesis of one or more globin chains or its part, which consequently results in reduced rate of synthesis of the haemoglobin. Whipple and Bradford in 1936 gave the term “Thalassaemia” [1]. -thalassaemia is commonly seen in Mediterranean region, Indian subcontinent, Southeast Asia, and African ancestry [1]. For -thalassaemia, screening of populations was done either by measuring the haemoglobin A2 percentage or by red cell indices in patients with MCV or MCH below a certain cut-off point [1]. The haemoglobin A2 is 4%-5% in most cases of heterozygous or severe thalassaemia and 3.6–4.2% in heterozygous mild thalassaemia [1]. The raised Hb A2 values are seen in unstable haemoglobins, hyperthyroidism, and megaloblastic anaemia, and human-immunodeficiency-virus- (HIV-) infected patients on antiretroviral therapy, while hypochromic microcytic red cell picture is seen only in heterozygous -thalassaemia [2]. History, clinical details, and coexisting condition help to rule out the causes of increase in Hb A2, which can avoid unnecessary investigation and reduce the financial burden of institutional setting in developing countries. Awareness of the fact that there are increases in Hb A2 due to antiretroviral drugs among clinicians and pathologists should be must. Spiga et al. reported that zidovudine inhibits -globin gene expression in human
References
[1]
B. J. Bain, Haemoglobinopathy Diagnosis, Blackwell Publishing, Malden, Mass, USA, 2nd edition, 2006.
[2]
J. Howard, J. S. Henthorn, S. Murphy, and S. C. Davies, “Implications of increased haemoglobin A2 values in HIV positive women in the antenatal clinic,” Journal of Clinical Pathology, vol. 58, no. 5, pp. 556–558, 2005.
[3]
M. Spiga, D. A. Weidner, C. Trentesaux, R. D. Leboeuf, and J. Sommadossi, “Inhibition of β-globin gene expression by 3′-azido-3′-deoxythymidine in human erythroid progenitor cells,” Antiviral Research, vol. 44, no. 3, pp. 167–177, 1999.
[4]
M. J. Wilkinson, B. J. Bain, L. Phelan, and A. Benzie, “Increased haemoglobin A2 percentage in HIV infection: disease or treatment?” AIDS, vol. 21, no. 9, pp. 1207–1208, 2007.
[5]
J.-P. Routy, M. Monte, R. Beaulieu, E. Toma, L. St-Pierre, and M. Dumont, “Increase of hemoglobin A2 in human immunodeficiency virus-1-infected patients treated with zidovudine,” American Journal of Hematology, vol. 43, no. 2, pp. 86–90, 1993.
[6]
F. Galacteros, F. Amaudric, C. Prehu et al., “Acquired unbalanced hemoglobin chain synthesis during HIV infection,” Comptes Rendus de l'Academie des Sciences. Series III, vol. 316, no. 4, pp. 437–440, 1993.
[7]
A. C. Gorakshakar and R. B. Colah, “Cascade screening for β-thalassemia: a practical approach for identifying and counseling carriers in India,” Indian Journal of Community Medicine, vol. 34, no. 4, pp. 354–356, 2009.
[8]
S. Rao, R. Kar, S. K. Gupta, A. Chopra, and R. Saxena, “Spectrum of haemoglobinopathies diagnosed by cation exchange-HPLC & modulating effects of nutritional deficiency anaemias from north India,” Indian Journal of Medical Research, vol. 132, no. 11, pp. 513–519, 2010.
[9]
G. Moyle, W. Sawyer, M. Law, J. Amin, and A. Hill, “Changes in hematologic parameters and efficacy of thymidine analogue-based, highly active antiretroviral therapy: a meta-analysis of six prospective, randomized, comparative studies,” Clinical Therapeutics, vol. 26, no. 1, pp. 92–97, 2004.
[10]
M. H. Steinberg and J. G. Adams III, “Hemoglobin A2: origin, evolution, and aftermath,” Blood, vol. 78, no. 9, pp. 2165–2177, 1991.
[11]
S. Pornprasert, P. Leechanachai, V. Klinbuayaem et al., “Effect of haematological alterations on thalassaemia investigation in HIV-1-infected Thai patients receiving antiretroviral therapy,” HIV Medicine, vol. 9, no. 8, pp. 660–666, 2008.
[12]
P. Kosalaraksa, S. Wiangnon, T. Bunupuradah, et al., “High HbA2 due to zidovudine exposure: implication for β-thalassemia trait screening,” in Proceedings of the 19th International AIDS Conference, Abstract no. MOPE045.
[13]
S. Pornprasert, K. Sukunthamala, P. Leechanachai, and T. Sanguansermsri, “Increased Hb A2 values in an HIV-1-infected patient receiving antiretroviral drugs: a pitfall for thalassemia antenatal diagnosis,” Hemoglobin, vol. 33, no. 2, pp. 158–161, 2009.
[14]
G. Stamatoyannopoulos, C. A. Blau, B. Nakamoto et al., “Fetal hemoglobin induction by acetate, a product of butyrate catabolism,” Blood, vol. 84, no. 9, pp. 3198–3204, 1994.
[15]
A. F. Collins, N. L. C. Luban, and G. J. Dover, “Increased fetal hemoglobin production in patients receiving valproic acid for epilepsy,” Blood, vol. 84, no. 5, pp. 1690–1691, 1994.
[16]
B. P. Alter and H. S. Gilbert, “The effect of hydroxyurea on hemoglobin F in patients with myeloproliferative syndromes,” Blood, vol. 66, no. 2, pp. 373–379, 1985.
