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ORIGINAL ARTICLE
Year : 2017  |  Volume : 20  |  Issue : 2  |  Page : 72-74

Effect of highly active antiretroviral therapy on neutrophil/lymphocyte ratio using white rabbit


1 Department of Medical Laboratory Science, School of Basic Medical Sciences, University of Benin, Benin City, Nigeria
2 Department of Anatomy, School of Basic Medical Sciences, University of Benin, Benin City, Nigeria

Date of Web Publication18-Sep-2017

Correspondence Address:
Evarista Odaburhine Osime
Department of Medical Laboratory Science, School of Basic Medical Sciences, University of Benin, Benin City
Nigeria
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DOI: 10.4103/1118-8561.215034

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  Abstract 

Background: There is an increasing reliance on neutrophil/lymphocyte ratio (NLR) as a prognostic marker in certain diseases. Observations have suggested the effects of administering highly active antiretroviral therapy (HAART) to human immunodeficiency virus (HIV) patients to be beneficial as well as having its side effects. Hence, this study is designed to examine the relationship of NLR of HAART in the management and disease progression of HIV infection. Materials and Methods: Twenty male white rabbits weighting between 0.8 and 1.8 kg were randomly assigned to five Groups A, B, C, D, and E with four animals per group. Two milliliters of venous blood was aseptically collected before HAART administration and on days 5, 10, 15, and 20 of treatment. Groups B, C, D, and E received graded doses of 15, 20, 25, and 34 mg/kg body weight of the drug combinations (efavirenz, lamivudine, and tenofovir disoproxil fumarate tablets once daily for 20 days). Neutrophil/lymphocyte counts were determined using hematology autoanalyzer. Results: Showed a significant reduction (P< 0.05) in NLR before HAART administration (controls) when compared to administration of HAART at 15, 20, 25, and 35 mg/kg 5 days after drug administration. The same trend was observed in the various groups at 10, 15, and 20 days after drug administration. Conclusion: Administration of HAART has a significant association on NLR.

Keywords: HAART, HIV, neutrophil/lymphocyte ratio


How to cite this article:
Osime EO, Innih SO. Effect of highly active antiretroviral therapy on neutrophil/lymphocyte ratio using white rabbit. Sahel Med J 2017;20:72-4

How to cite this URL:
Osime EO, Innih SO. Effect of highly active antiretroviral therapy on neutrophil/lymphocyte ratio using white rabbit. Sahel Med J [serial online] 2017 [cited 2019 Oct 15];20:72-4. Available from: http://www.smjonline.org/text.asp?2017/20/2/72/215034


  Introduction Top


Antiretroviral (ARV) drugs are extensively used in the management of infections caused by the human immunodeficiency virus (HIV). To effectively combat and treat this illness a combination of three of these drugs are used. This combination is generally referred to as highly active antiretroviral therapy (HAART). The American National Institute of health and other organizations recommend ARV treatment to all patients with AIDS. While the USA and European guidelines strongly recommend ARV initiation, if the CD4 count is <350 cells/mm 3.[1],[2] Antiretroviral therapy (ART) is also strongly recommended in certain groups of patients regardless of CD4 count, such as pregnant women, those with hepatitis B infection and patients with HIV-associated nephropathy.[3] It is a well-known fact that ART cannot eradicate HIV infection. It can, however, reduce HIV replication to extremely low levels and allow the restoration of immune function to safe levels in the majority of treated persons. It has been reported that a high neutrophil/lymphocyte ratio (NLR) is associated with a higher risk of cardiovascular disease (CVD).[4] The main finding of that study was that a higher NLR was associated with increased risk for CVD-related events, both in terms of shorter duration from the start of the dialysis therapy to the first CVD event and a large number of cumulative CVD events during the follow-up time. A reliable risk prediction marker is necessary for any strategy aiming at reducing the high premature mortality in patients. Furthermore, prompt access to results, simplicity, and low cost would be an additional feature requested in a clinical setting. In general, NLR is a simple risk prediction marker for evaluating the combined impact of both inflammation and impaired nutritional status, without needing a special tool or technique.[5] Little is known and published about NLR and its relationship with prevalent chronic conditions among the general population. The aim of this work is, therefore, to examine the effect of different doses of HAART on NLR and to suggest its use as a follow-up marker to monitor drug intake.


  Materials and Methods Top


This study was carried out in the Department of Medical Laboratory Science, College of Medicine, University of Benin and University of Benin Animal House from September to November 2014.

Twenty white male rabbits weighing between 0.8 and 1.8 kg were randomly assigned to five Groups A, B, C, D, and E with four animals per group. Group A rabbits did not receive any drug and served as controls while Groups B, C, D, and E rabbits received doses of 15, 20, 25, and 35 mg/kg combination of efavirenz, lamivudine, and tenofovir disoproxil fumarate tablets once daily for 20 days. Drug administration was done through oral intubation using gavage technique. At the end of drug administration, each rabbit was bled painlessly under chloroform anesthesia from the marginal vein of the ear at 5 days interval. Neutrophil and lymphocyte counts were determined using a hematology auto analyzer (ERMA ing pce-210) model while NLR was calculated by dividing the number of neutrophils by the number of lymphocytes. Results obtained were presented as mean ± standard error subjected to statistical analysis using Student's t-test and one-way analysis of variance to determine significance differences between means.


  Results Top


This showed a significant reduction (P< 0.05) in NLR in Groups B, C, D, and E when compared to Group A. The same trend was observed in the various groups at 10, 15, and 20 days after drug administration [Table 1], [Table 2], [Table 3], [Table 4].
Table 1: Neutrophil/lymphocyte ratio after 5 days of highly active antiretroviral therapy administration

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Table 2: Neutrophil/lymphocyte ratio after 10 days of highly active antiretroviral therapy administration

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Table 3: Neutrophil/lymphocyte ratio after 15 days of highly active antiretroviral therapy administration

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Table 4: Neutrophil/lymphocyte ratio after 20 days of highly active antiretroviral therapy administration

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  Discussion Top


White blood cell (WBC) count is a crude but cheap and sensitive method of assessing inflammatory status.[6] WBCs are positively associated with inflammation, particularly in CVDs.[7] The NLR in complete blood counts tests is a potential marker for both cardiac and noncardiac disorders.[8] In this paper, we examined the NLR of HAART using white rabbit. There was a significant decrease (P< 0.05) in the NLR after administration of 15 mg/kg and this increased as the dose administered increased at 20 and 25 mg/kg, respectively. A probable explanation is the cellular response of these blood components mediated through the endothelial dysfunction caused by the introduction of HAART. The NLR was also observed to reduce significantly (P< 0.05) when the dose administered was increased to 35 mg/kg on day 5 of drug administration. This could be attributed to the fact that the animals must have gotten used to the drug through a negative feedback mechanism.[9]

It has been observed that neutrophilia and lymphocytopenia are independent predictors of many diseases such as acute heart failure,[10] and may be examined routinely to monitor disease and drug progression to the best of our knowledge no work has been done on the effect of HAART on NLR. On comparison of NLR after 10 days of administration of HAART, there was a significantly reduction (P< 0.05) in NLR by administration of 15 mg/kg (Group B) and 20 mg/kg (Group C) when compared to the control groups (Group A). This could be attributed to the direct effect of these drugs (HAART) on neutrophil/lymphocyte progenitor cells causing a seemingly depressed bone marrow activity which is observed to improve as the body recognizes and adapts to the drug administration. This also goes to explain the increase in NLR as the dose administered increased.

Comparisons were also done at day 15 and day 20 of drug administration. A significant reduction (P< 0.05) was observed between the controls (Group A) and test Groups B, C, D, and E, respectively. Although no particular trend was noted, we, however, observed that at each stage of drug administration there was a reduction in NLR and these could be attributed directly to the effect of HAART on hematopoiesis.

As earlier mentioned, the introduction of HAART has greatly improved the hemopoietic status and lifestyles of HIV-infected patients. A reliable predictor marker is necessary for any strategy aiming at reducing the high premature mortality in these patients, while prompt access to result, simplicity, and low cost would be additional features requested in the clinical setting.


  Conclusion Top


NLR is widely used to identify high-risk patients with various illnesses and to monitor drug outcomes. The NLR levels are reduced during the administration of HAART. We suggest that NLR should be used to monitor HAART outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Nubila T, Ukaejiofo EO, Nabila NI, Okore GI. Examination of haematotoxicity of fixed-dose highly active antiretroviral drug in albino wistar rats. Int Sch Res Netw 2012;6:64-70.  Back to cited text no. 1
    
2.
UNAIDS. Report on the Global AIDS Epidemic Geneva: Joint United Nations Programmes on HIV/AIDS; 2010. Available from: http//www.unaids.org/global report. [Last Retrieved on 2016 Mar 7].  Back to cited text no. 2
    
3.
Soilleux EJ, Coleman N. Transplacental transmission of HIV: A potential role for HIV binding lectins. Int J Biochem Cell Biol 2003;35:283-7.  Back to cited text no. 3
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4.
Abe T, Kato S, Tsuruta Y, Sugura S, Katsino T, Kosigo T. Nuetrophil lymphocyte ratio as a predictor of cardiovascular events in incident dialysis patients: A Japanese prospective cohort study. Clin Exp Nephrol 2014;52:332-50.  Back to cited text no. 4
    
5.
Gibson PH, Croal BL, Cuthbertson BH, Small GR, Ifezulike AI, Gibson G, et al. Preoperative neutrophil-lymphocyte ratio and outcome from coronary artery bypass grafting. Am Heart J 2007;154:995-1002.  Back to cited text no. 5
    
6.
Sawako K, Tomoko A, Bengt L, Shoichi M. Neutrophil/lymphocyte ratio: A promising prognostic marker in patients with chronic kidney disease. Inf cell Signal 2015;2:683.  Back to cited text no. 6
    
7.
Miyamoto T, Carrero JJ, Stenvinkel P. Inflammation as a risk factor and target for therapy in chronic kidney disease. Curr Opin Nephrol Hypertens 2011;20:662-8.  Back to cited text no. 7
    
8.
Sanderson JE, Mayosi B, Yusuf S, Reddy S, Hu S, Chen Z, et al. Global burden of cardiovascular disease. Heart 2007;93:1175.  Back to cited text no. 8
    
9.
Umar RA, Ladan MJ, Hassan SW, Sa'id Y, Abbas AY, Oduolisaeme IB. Administration of antiretroviral drugs (lamivudine, nevirapine and stavudine) has no untoward effect on haematological profile in albino rats. Asian J Biochem 2007;2:147-51.  Back to cited text no. 9
    
10.
Folsom AR, Rosamond WD, Shahar E, Cooper LS, Aleksic N, Nieto FJ, et al. Prospective study of markers of hemostatic function with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation 1999;100:736-42.  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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