Highly active antiretroviral therapy (HAART) is considered toxic and has other life-threatening side effects. Our aim was to evaluate the haematotoxic effects of lamivudine, zidovudine, and nevirapine fixed-dose combinations in Albino Wistar rats. Fifty (50) three (3) months old male Albino Wistar rats weighing between 200 and 250 g were randomly assigned to five (5) groups (A, B, C, D, and E). Group A served as control. Two (2 mLs) of venous blood was aseptically collected on Days 5, 10, 15, 20, and 25 of treatment. Red blood cell (RBC) mean value recorded statistically significant increase (
Antiretroviral drugs are medication for treatment of infection by retroviruses, primarily human immunodeficiency virus (HIV). When several such drugs, typically three or four, are taken in combination, the approach is known as highly active antiretroviral therapy, or HAART. The American National Institute of Health and other organizations recommend offering antiretroviral treatment to all patients with AIDS. Because of the complexity of selecting and following a regimen, the severity of the side effects and the importance of compliance to prevent viral resistance, such organizations emphasize the importance of involving patients in therapy choices and recommend analyzing the risks and the potential benefits to patients with low viral loads [
There is no doubt that HAART has been the most important progress in the therapy of HIV-infected patients in the last decade. A growing number of observations suggest that the beneficial effects of HAART also include improvement of HIV-related haematological complications [
The values of haematologic parameters are affected by a number of factors even in apparently healthy populations. These factors include age, sex, ethnic background, body build, and social, nutritional, and environmental factors, especially altitude [
The three (3) fixed-dose antiretroviral combination drugs used for the study were obtained from one of the accredited United States Presidential Emergency Plan for AIDS Relief (PEPFAR) centers in Enugu, Enugu State, Nigeria. The HAART considered in the study was a fixed-dose combinations (FDCs) of lamividine (150 mg), zidovudine (300 mg), and nevarapine (200 mg) per tablet. The drug was manufactured by Aurobindo Pharma Limited, Unit III, survey No. 313, Bachupally village, Quthubullapur Mandal, Ranga Reddy District (A.P) India.
This was according to the guidelines issued by World Health Organization (WHO), Geneva, Switzerland and the Indian National Science Academy (INSA), New Delhi, India on the care and use of laboratory animals. The Albino Wistar rats which were three (3) months old and weighing 200–250 g were selected from the colony maintained under the controlled conditions of temperature (
Fifty (50) three (3) months old male Albino Wistar rats weighing between 200–250 g were randomly assigned to five (5) groups (A, B, C, D, and E) according to similar body weight with ten (10) animals per group. Groups B, C, D, and E received graded doses (3, 6, 12, and 24 mg/Kg body weight, resp.) once daily for twenty five (25) days. Group A served as control. All administrations were by oral intubation.
Two (2 mLs) of venous blood was aseptically collected on Days 5, 10, 15, 20, and 25 of treatment after overnight fasting from each animal into tripotassium ethylene diamine tetra acetic acid (K3EDTA) anticoagulant bottle. This was immediately mixed by gentle inversion and used in the determination of the haematological profile using a haematology auto analyser (Sysmex KX-2IN) following the manufacturer’s guidelines. The samples were analysed within two hours of collection. Two (2) animals were bled painlessly under chloroform anesthesia by ocular puncture through the retro-bulber plexus of the medial canthus.
Data were analysed using Students’ “
Red blood cells (RBCs) count mean value recorded statistically significant increase (
Comparison of the mean ± S.E of the haematological parameters after 5 days of HAART administration with the control group.
Parameter | Group A |
Group B |
Group C |
Group D |
Group E |
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RBC (×1012/L) |
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HB (g/dL) |
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PCV (L/L) |
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MCHC (g/dL) |
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MCV (fL) |
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MCH (pg) |
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RETICS (%) |
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PLAT (×109/L) |
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WBC (×109/L) |
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NEUT (%) |
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LYMPH (%) |
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EOS (%) |
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MONO (%) |
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BAS (%) |
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RBC: red blood cell, HB: haemoglobin concentration, PCV: packed cell volume, MCHC: mean cell haemoglobin concentration, MCV: mean cell volume, MCH: mean cell haemoglobin, RETICS: reticulocytes, PLAT: platelets, WBC: white blood cell, NEUT: neutrophils, LYMPH: lymphocytes, EOS: eosinophils, BAS: basophils.
However, RBC, haemoglobin (Hb), and packed cell volume (PCV) recorded statistically significant decrease (
Comparison of the mean ± S.E of the haematological parameters after 10 days of HAART administration with the control group.
Parameter | Group A |
Group B |
Group C |
Group D |
Group E |
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RBC (×1012/L) |
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HB (g/dL) |
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PCV (L/L) |
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MCHC (g/dL) |
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MCV (fL) |
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MCH (pg) |
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RETICS (%) |
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PLAT (×109/L) |
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WBC (×109/L) |
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NEUT (%) |
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LYMPH (%) |
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EOS (%) |
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MONO (%) |
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BAS (%) |
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RBC: red blood cell, HB: haemoglobin concentration, PCV: packed cell volume, MCHC: mean cell haemoglobin concentration, MCV: mean cell volume, MCH: mean cell haemoglobin, RETICS: reticulocytes, PLAT: platelets, WBC: white blood cell, NEUT: neutrophils, LYMPH: lymphocytes, EOS: eosinophils, BAS: basophils.
*Compared with the control group *
Only platelet count mean value recorded a dose-dependent statistically significant increase (
Comparison of the mean ± S.E of the haematological parameters after 15 days of HAART administration with the control group.
Parameter | Group A |
Group B |
Group C |
Group D |
Group E |
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RBC (×1012/L) |
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HB (g/dL) |
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PCV (L/L) |
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MCHC (g/dL) |
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MCV (fL) |
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MCH (pg) |
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RETICS (%) |
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PLAT (×109/L) |
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WBC (×109/L) |
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NEUT (%) |
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LYMPH (%) |
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EOS (%) |
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MONO (%) |
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BAS (%) |
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RBC: red blood cell, HB: haemoglobin concentration, PCV: packed cell volume, MCHC: mean cell haemoglobin concentration, MCV: mean cell volume, MCH: mean cell haemoglobin, RETICS: reticulocytes, PLAT: platelets, WBC: white blood cell, NEUT: neutrophils, LYMPH: lymphocytes, EOS: eosinophils, BAS: basophils.
In addition, there was no statistically significant difference (
Comparison of the mean ± S.E of the haematological parameters after 20 days of HAART administration with the control group.
Parameter | Group A |
Group B |
Group C |
Group D |
Group E |
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RBC (×1012/L) |
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HB (g/dL) |
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PCV (L/L) |
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MCHC (g/dL) |
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MCV (fL) |
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MCH (pg) |
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RETICS (%) |
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PLAT (×109/L) |
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WBC (×109/L) |
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NEUT (%) |
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LYMPH (%) |
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EOS (%) |
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MONO (%) |
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BAS (%) |
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RBC: red blood cell, HB: haemoglobin concentration, PCV: packed cell volume, MCHC: mean cell haemoglobin concentration, MCV: mean cell volume, MCH: mean cell haemoglobin, RETICS: reticulocytes, PLAT: platelets, WBC: white blood cell, NEUT: neutrophils, LYMPH: lymphocytes, EOS: eosinophils, BAS: basophils.
However, only total WBC showed a statistically significant decrease (
Comparison of the mean ± S.E of the haematological parameters after 25 days of HAART administration with the control group.
Parameter | Group A |
Group B |
Group C |
Group D |
Group E |
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RBC (×1012/L) |
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HB (g/dL) |
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PCV (L/L) |
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MCHC (g/dL) |
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MCV (fL) |
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MCH (pg) |
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RETICS (%) |
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PLAT (×109/L) |
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WBC (×109/L) |
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NEUT (%) |
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LYMPH (%) |
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EOS (%) |
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MONO (%) |
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BAS (%) |
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RBC: red blood cell, HB: haemoglobin concentration, PCV: packed cell volume, MCHC: mean cell haemoglobin concentration, MCV: mean cell volume, MCH: mean cell haemoglobin, RETICS: reticulocytes, PLAT: platelets, WBC: white blood cell, NEUT: neutrophils, LYMPH: lymphocytes, EOS: eosinophils, BAS: basophils.
*Compared with the control group *
Furthermore, in group C, RBC, and Hb mean values demonstrated a time-dependent statistically significant increase (
One way ANOVA of the mean ± S.E haematological parameters of the rats administered 12 mg/Kg body weight (Group C) of HAART on Days 5, 10, 15, 20, and 25.
Parameter | Day 5 | Day 10 | Day 15 | Day 20 | Day 25 |
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RBC (×1012/L) |
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HB (g/dL) |
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PCV (L/L) |
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MCHC (g/dL) |
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MCH (pg) |
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MCV (fL) |
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RETICS (%) |
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PLAT (×109/L) |
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WBC (×109/L) |
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NEUT (%) |
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LYMPH (%) |
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EOS (%) |
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MONO (%) |
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BAS (%) |
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RBC: red blood cell, HB: haemoglobin concentration, PCV: packed cell volume, MCHC: mean cell haemoglobin concentration, MCV: mean cell volume, MCH: mean cell haemoglobin, RETICS: reticulocytes, PLAT: platelets, WBC: white blood cell, NEUT: neutrophils, LYMPH: lymphocytes, EOS: eosinophils, BAS: basophils.
*Compared with the control group *
Although HAART has dramatically improved survival in HIV patients, precautions still need to be taken to prevent HAART-related haematotoxicity and other life threatening side effects. In this study, red blood cell (RBC) mean value recorded statistical significant increase (
There was no statistically significant difference (
There was a time-related statistically significant increase (
Hence, from the result of this present study, it can be concluded that HAART when administered in fixed-dose combinations have no subacute haematotoxic effects. Its use in the treatment of HIV and other viral related infection should be encouraged and haematological parameters should be monitored.