Causes of Macrocytosis in HIV-infected Patients not Treated with Zidovudine

doi:10.1053/jinf.1999.0628

Journal of Infection

Volume 40, Issue 2, March 2000, Pages 160-163

https://doi.org/10.1053/jinf.1999.0628 Get rights and content

Abstract

Objective: Zidovudine is a well known cause of macrocytosis. However, many HIV-infected patients develop macrocytosis even though they do not receive zidovudine. The aim of this case-control study was to evaluate other causes of high mean corpuscular volumes (MCV) in HIV infected patients.

Methods: Thirty patients with a MCV≥100 fl (cases) were compared to 60 randomly selected controls with MCV≤99 fl, none of them receiving zidovudine.

Results: Sex ratio, age, mean CD4, prevalence of alcohol abuse and liver disease were similar in both groups. Vitamin B12 or folic acid levels were not decreased in patients with macrocytosis. In contrast, there was an association between macrocytosis and use of stavudine alone or in combination with another antiviral drug (28/30 cases, 15/60 controls, odds ratio 40.6 (95% confidence interval 5.1-325.2), P≤0.001). The haemoglobin concentration among cases (mean 13.5 g/dl) was similar to that of controls (mean 13.0 g/dl).

Conclusions: Stavudine use increase the risk of macrocytosis more than 40-fold in HIV-infected patients who do not receive zidovudine. None of the stavudine-treated patients, however, developed anaemia or had to interrupt treatment because of this side effect.

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In HIV patients receiving a zidovudine-based HAART regimen, MCV has been shown to increase significantly after one month of HAART exposure; the development of macrocytosis could be used as an adherence indicator to reflect the treatment effectiveness [12,13]. Macrocytosis has also been reported in patients taking other NRTIs, such as stavudine and lamivudine, but to a lesser degree [12,14,15]. In brief, drug-induced impairment of DNA synthesis is expected to be a mechanism of megaloblastic change [16].
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La macrocitosis y las anemias macrocíticas constituyen un problema asistencial frecuente. Las principales causas de macrocitosis pueden agruparse en dos grandes grupos: las anemias megaloblásticas, producidas por un defecto en la síntesis de ADN, siendo las causas más frecuentes los déficits adquiridos de vitamina B₁₂ y/o ácido fólico y algunos fármacos, y las no megaloblásticas. Las causas más frecuentes de estas últimas son el consumo de alcohol, la hepatopatía, la reticulocitosis y el hipotiroidismo. Una historia clínica pormenorizada, junto con un estudio morfológico de la sangre periférica y un recuento de reticulocitos son esenciales para una orientación de los pacientes con macrocitosis. Basándose en la sospecha diagnóstica se requerirá la realización de otras pruebas confirmatorias. El tratamiento de las anemias macrocíticas incluye tres aspectos: el tratamiento etiológico, el tratamiento de soporte, que incluye fundamentalmente las transfusiones, y el tratamiento sustitutivo en caso de que exista un déficit.
Macrocytosis and macrocytic anemias, defined as anemias with a mean corpuscular volume greater than 100 fl, are common problems. There are two major groups of macrocytosis: the megaloblastic anemias, disorders of DNA synthesis of the erythrocyte precursors, being the most frequent causes a vitamin B₁₂ and/or folic acid deficiencies and certain drugs, and the non-megaloblastic ones. The most common etiologies of these are alcoholism, hypothyroidism, reticulocytosis, ethanol abuse, liver disease, as well as exposure to some medications. A detailed clinical history together with a peripheral smear and a reticulocyte count are essential tools for delineating the underlying cause of the macrocytosis. Based on the suspected etiology additional confirmatory tests will be required. Treatment of macrocytosis and or macrocytic anemia involves three aspects: the etiologic treatment, a supportive treatment that is essentially based on transfusions, and a substitute treatment when required.
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People with AIDS have multiple risk factors for anemia, including use of myelosuppressive drugs, poor nutritional status, and blood loss from gastrointestinal lesions.35 They commonly have other hematologic abnormalities as well, including macrocytosis, which is associated with vitamin B12 or folate deficiency from intestinal malabsorption and with use of certain medications, such as zidovudine, stavudine, and ganciclovir.35,36 We found that high MCV is independently related to the narrowing of retinal venules.
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We evaluated data for participants without ocular opportunistic infections at initial examination (baseline) in the Longitudinal Studies of the Ocular Complications of AIDS (1998–2008). Semi-automated evaluation of fundus photographs (1 eye/participant) determined central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) at baseline. Multiple linear regression models, using forward selection, identified independent relationships between indices and various host- and disease-related variables.
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Regular ArticleCauses of Macrocytosis in HIV-infected Patients not Treated with Zidovudine

Abstract

Megaloblastic anemias

Harrison's Principles of Internal Medicine, 14th edition

Changing etiology of macrocytosis

Am J Clin Pathol

The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex

N Eng J Med

Stavudine induced macrocytosis (letter)

Genitourin Med

Regular Article
Causes of Macrocytosis in HIV-infected Patients not Treated with Zidovudine