|
 
 |
| ORIGINAL ARTICLE |
|
| Year : 2013 | Volume
: 2
| Issue : 3 | Page : 162-166 |
|
Elevated activities of serum lactate dehydrogenase in human immunodeficiency virus sero-positive patients in highly active antiretroviral therapy era
KV Ramana1, Ratna Rao1, Sabitha Kandi2, Purna A Singh3, Vankata Bharath P Kumar4
1 Department of Microbiology, Apollo Health City, Jubilee Hills, Hyderabad, Andhra Pradesh, India
2 Department of Biochemistry, Chalmeda Anandarao Institute of Medical Sciences, Bommakal, Karimnagar, Andhra Pradesh, India
3 Department of Physiology, Mamatha Medical College, Khammam, Andhra Pradesh, India
4 Department of Biochemistry, Vaidehi Institute of Medical Sciences and Research Center, Bangalore, Karnataka, India
| Date of Web Publication | 29-Aug-2013 |
Correspondence Address:
K V Ramana
Apollo Health City, Jubilee Hills, Hyderabad, Andhra Pradesh
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2277-8632.117180
Background: Monitoring HIV disease progression and deciding the time to initiate highly active antiretroviral therapy (HAART) requires evaluation of TCD4 + cell counts and HIV/RNA viral load at regular intervals. Considering the fact that it is the resource restrained developing countries that carry most of the burden of HIV, recently, studies have been carried out to evaluate the utility of low cost, easily performed alternate biomarkers that can be used for HIV disease management and in response to HAART. Unavailability of scientific technology and inadequate infrastructure makes it difficult for resource poor countries to manage HIV-infected individuals.
Aim: Our study concentrated on evaluating LDH activities in HIV-infected individuals on HAART.
Materials and Methods: The study was conducted between June 2011 to December 2011, and 36 HIV seropositive and antiretroviral therapy naive individuals and 21 HIV seropositive patients presently on HAART since past 3-6 months attending Integrated Counseling and Testing Centre (ICTC) situated at Area hospital Siddipet were enrolled in the study.
Results: Our study concentrated on evaluating LDH activities in HIV-infected individuals (220.42 ± 79.04 IU/L) on HAART and showed that higher serum LDH activities were found when compared to controls (160.13 ± 47.11 IU/L). After 3–6 months of HAART, the serum LDH showed statistically significant decrease (188.76 ± 42.91 IU/L) (P < 0.002).
Conclusion: LDH assay is useful in monitoring HIV disease progression and treatment response. Keywords: Highly active antiretroviral therapy, human immunodeficiency virus, lactate dehydrogenase
How to cite this article:
Ramana K V, Rao R, Kandi S, Singh PA, Kumar VP. Elevated activities of serum lactate dehydrogenase in human immunodeficiency virus sero-positive patients in highly active antiretroviral therapy era. J NTR Univ Health Sci 2013;2:162-6 |
How to cite this URL:
Ramana K V, Rao R, Kandi S, Singh PA, Kumar VP. Elevated activities of serum lactate dehydrogenase in human immunodeficiency virus sero-positive patients in highly active antiretroviral therapy era. J NTR Univ Health Sci [serial online] 2013 [cited 2021 Jan 17];2:162-6. Available from: https://www.jdrntruhs.org/text.asp?2013/2/3/162/117180 |
| Introduction | |  |
With the introduction of highly active antiretroviral therapy (HAART), HIV disease has taken a different course, wherein there has been marked reduction in the mortality of HIV-infected individuals. [1] However, morbidity implicated to the non-infectious complications has been a cause of concern. [2] Although pathogenicity of HIV is least understood, HIV infection by itself leads to disturbed metabolism of involved cells and may cause severe oxidative stress and invariably cell death. [3] HIV-infected individuals now have almost free access to HAART both in developed and developing countries. HIV disease has reemerged in HAART era shifting from infectious complications to non-infectious morbidity. [4] Management of HIV infection, treatment response, and thereby disease progression involves regular monitoring of TCD4+ cell counts and HIV/RNA viral load. [5] Unavailability of scientific technology and inadequate infrastructure makes it difficult for resource poor countries to manage HIV-infected individuals. Considering the fact that it is the developing nations that carry most of the burden of HIV-infected individuals, research is now concentrated on finding cost-effective biomarkers that can be used for monitoring HIV disease progression and treatment response. [6] We have attempted to evaluate utility of lactate dehydrogenase (LDH) in monitoring HIV disease progression.
LDH (EC 1.1.1.27, L-Lactate: NAD + oxidoreductase) is an enzyme that is present both in plants animals (both vertebrates and invertebrates) and other microorganisms including bacteria and yeast. [7],[8],[9],[10],[11] LDH plays a significant role in glucose metabolism and is seen in various isoenzyme (LDH1-5) forms in different organs of the body coded on genes. LDH generates temporary oxygen from lactate in the absence of oxygen and later converts lactate to pyruvate when oxygen is available. LDH plays a critical role in maintaining optimum ratios of NAD/NADH in various organs of the body including the heart, brain, skeletal muscles, and other tissues. [7] Tissue injury, disturbed cell metabolism due to anoxia, cancers, and many other infectious and non-infectious conditions may trigger release of high activities of LDH in to the blood stream. [12] HAART by itself has been shown to be responsible for toxic effects on various organs and their role in inflammatory response may contribute to increased activities of LDH in HIV-infected individuals. [13] We have attempted to evaluate utility of LDH in monitoring HIV disease progression and treatment response.
| Materials and Methods | | |
The study was conducted between June 2011 and December 2011, which included 36 HIV seropositive and antiretroviral therapy naive individuals and 21 HIV seropositive patients presently on HAART since past 3-6 months attending Integrated Counseling and Testing Centre (ICTC) situated at Area hospital Siddipet were enrolled in the study. A total of 25 normal healthy individuals are included in the study as controls. The mean ± SD of age group included was 36.33 ± 11.67 years for cases and 35.92 ± 12.98 years for controls. Gender of the cases (54.4% of male and 45.6% females) were matched with control group. All the subjects included in the study were provided with a proforma with details of the study and an informed and written consent was obtained. Blood samples were collected following standard laboratory procedures and stored under −20°C. Their HIV status was confirmed following National Aids Control Organization (NACO) guidelines using three different ELISA methods (NACO, 2006). [14] Serum LDH was evaluated by enzymatic method using Diasys kits in an automatic analyzer.
Statistical methods
The Statistical software namely SAS 9.2, SPSS 15.0, Stata 10.1, MedCalc 9.0.1, Systat 12.0, and R environment ver.2.11.1 were used for the analysis of the data and Microsoft word and Excel were used to generate graphs and tables. Descriptive statistical analysis has been carried out in the present study. Results on continuous measurements are presented on mean ± SD (Min-Max) and results on categorical measurements are presented in Number (%). Significance is assessed at 5% level of significance. The following assumption on data has been made, Assumptions: 1. Dependent variables should be normally distributed, 2. Samples drawn from the population should be random, and Cases of the samples should be independent.
Analysis of variance (ANOVA) has been used to find the significance of study parameters between three or more groups of patients and Student t-test (two tailed, independent) has been used to find the significance of study parameters on continuous scale between two groups (Inter group analysis) on metric parameters. Leven1s test for homogeneity of variance has been performed to assess the homogeneity of variance. Chi-square/Fisher Exact test has been used to find the significance of study parameters on categorical scale between two or more groups.
| Results | | |
The results revealed a significant variation in serum activities of serum LDH among the HIV seropositive patients who are antiretroviral therapy naïve (220.42 ± 79.04 IU/L) and those on HAART for at least 3–6 months (188.76 ± 42.91 IU/L) as compared with normal healthy individuals (160.13 ± 47.11 IU/L), as shown in [Table 1]. Graph depicting LDH activities in different study groups was shown in [Figure 1]. Receiver operating curve (ROC) analysis was performed at a cut off of >172 to evaluate the sensitivity, specificity, and accuracy of serum LDH in HIV disease and progression, as shown in [Figure 2] and [Table 2].
| Discussion | | |
The study results clearly demonstrate elevated activities of serum LDH in HIV-infected individuals as compared to normal controls. LDH activities among the HIV-infected individuals and those on HAART were comparatively lower than those not receiving HAART. Results of the present study also indicate that initiation of HAART may reduce the activities of LDH, thereby suggesting good prognosis. LDH is an enzyme that is found in higher concentrations when there is damage to the tissues either in acute conditions like in a case of trauma or chronic conditions including liver disease and hemolytic anemia. Autoimmune conditions like myasthenia gravis and infectious conditions including meningitis, encephalitis, histoplasmosis, and pneumocystitis have been attributed to rise in the activities of serum LDH. Activities of LDH in the serum are also increased by drugs like aspirin, clofibrate, fluorides, procainamide, mithramycin, narcotics, and anesthetics. thValencia et al ., have demonstrated that a serum LDH activities of >460 IU/L correlated well with AIDS status (P < 0.05). Study also revealed that serum LDH was considerably raised in non-AIDS HIV seropositive patients with tuberculosis and pneumocystitis infection. [15] thButt et al ., in their study compared the TCD4+ cell counts with serum LDH and the presence of opportunistic infection. This study revealed a higher serum LDH (>225 IU/L) in patients with TCD4+ cell counts less than 200 cells/mm 3 (P < 0.01). [16] thVaccher et al ., in their study revealed that higher serum LDH levels, age more than 40 years, and having opportunistic infection with TCD4+ cell counts <100 cells/mm 3 have greater influence on shortened survival (PS > or = 2). Study has confirmed the role of serum LDH as an independent prognostic marker along with TCD4+ cell counts in HIV disease management. [17] thSilverman et al ., in their study of 33 AIDS/AIDS-related complex patients have revealed that elevated serum LDH was correlating well with AIDS status. [18] Peters et al., in their study involving four cases of AIDS patients with TCD4+ cell counts of <50 cells/mm 3 revealed a serum LDH >600 IU/L and correlated with disseminated histoplasmosis (75%). [19] Gutierrez et al., observed that a 3 times increase in serum LDH in HIV seropositive patients correlated well with disseminated histoplasmosis. [20] Vogela et al., in their study showed that elevated serum LDH correlated well with pneumocystis carinii pneumonia (PCP) (pneumocystis jiroveci pneumonia). [21] Quist et al., in their study observed that elevated serum LDH does not necessarily indicate infection with PCP and that HIV seropositive patients without pneumocystitis also had raised serum LDH. [22] Our study concentrated on evaluating LDH levels in HIV-infected individuals and showed that higher serum LDH activities were found when compared to controls. Further studies should concentrate on evaluating the efficacy of LDH in assessing the HIV disease progression and treatment response. Initiation of HAART has considerably reduced the mortality and the morbidity associated with HIV infection. Currently in India, approximately 3 lakh HIV seropositive individuals have access to HAART and it has been noted that the new HIV cases have shown a downtrend, except for few states that have recorded more cases including Andhra Pradesh and Tamil Nadu. [23] The present study included HIV seropositive patients who were recently diagnosed after voluntary testing in an Integrated Counseling and Testing Center (ICTC). Most of the patients diagnosed had no acute infectious or non-infectious clinical symptoms. Most of the previous studies have been in advanced HIV disease or AIDS patients and several studies have demonstrated the role of serum LDH in association with lung infection with PCP now termed as pneumocystis jeroveci pneumonia and histoplasmosis. [24]
Considering the fact that HIV disease course is very complex and may be different in infected population, it must be noted that not always TCD4+ cell counts and HIV/RNA viral load estimation gives a clear picture on the immunological status of the patients. Having reviewed the existing literature, it is clear that LDH activities indicate both infectious and inflammatory activity in various organs of the body. HIV-infected patients suffer from various infections because of which continuous inflammatory responses are initiated resulting in cell damage. Studies have also confirmed the role of toxic effects of HAART in initiating inflammation. This study revealed the usefulness of evaluating LDH activities for disease prognosis and management in HIV-infected patients who were on HAART.
| Conclusion | | |
Monitoring HIV disease progression, deciding the time to initiate HAART requires evaluation of CD4 cell counts and HIV/RNA viral load. Considering the fact that it is the resource restrained developing countries that carry most of the burden of HIV, studies recently have been carried out to evaluate the utility of low cost, easily performed alternate biomarkers that can be used for HIV disease management and response to HAART therapy. We therefore recommend evaluation of such biomarkers on large scale studies with multi-center cohort studies involving HIV seropositive patients and those on HAART.
| Acknowledgements | | |
We express our sincere gratitude to Dr. NTR University of Health Sciences, Vijayawada, Andhra Pradesh, India and to Dr. K. P. Suresh, PhD (Biostatistics) Scientist (SS), Project Directorate on Animal Disease Monitoring and Surveillance (PDADMAS) Hebbal, Bangalore, for reviewing the statistics.
| References | | |
| 1. | Venkat A, Piontkowsky DM, Cooney RR, Srivastava AK, Suares GA, Heidelberger CP. Care of the HIV-positive patient in the emergency department in the era of highly active antiretroviral therapy. Ann Emerg Med 2008;52:274-85. 
[PUBMED] |
| 2. | Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998;338:853-60.
[PUBMED] |
| 3. | Woods MN, Wanke CA, Ling PR, Hendricks KM, Tang AM, Andersson CE, et al. Metabolic syndrome and serum fatty acid patterns in serum phospholipids in hypertriglyceridemic persons with human immunodeficiency virus. Am J Clin Nutr 2009;89:1180-7.
[PUBMED] |
| 4. | Ramana KV, Mohanty SK. Opportunistic intestinal parasites and TCD4 + cell counts in human immunodeficiency virus seropositive patients. J Med Microbiol 2009;58:1664-6.
[PUBMED] |
| 5. | Ramana KV. HIV Disease Management in the Highly Active Antiretroviral Therapy (HAART) era. J Med Microbiol Diagn 2012;1:e101.
|
| 6. | Ramana KV, Ratna R, Sabitha, Venugopal B, Rafi MD. Biochemical parameters in human immunodeficiency virus disease progression. J Med Microbiol Diagn 2012;1:103.
|
| 7. | Clement L, Markert CL. Lactate dehydrogenase biochemistry and functions of lactate dehydrogenase. Cell Biochemistry and Function. London: Butterworth and Co. (Publishers) Ltd; 1984. p. 2.
|
| 8. | Nada C, Ginard B, Markert CL. lsozymes II physiological function. In: Markert CL, editor. vol. 11. New York: Academic Press; 1975. p. 45-64.
|
| 9. | Ellington WR, Long GL. Purification and characterization of a highly unusual tetrameric D-lactate dehydrogenase from the muscle of the giant barnacle, Balanus nubilus Darwin. Arch Biochem. Biophys 1978;186:265-74.
|
| 10. | Oba K, Murakami S, Uritani I. Partial purification and characterization of L-Lactate dehydrogenase isozymes from sweet potato roots. J Biochem 1977;81:1193-201.
[PUBMED] |
| 11. | Hensel R, Mayr U, Yang CY. The complete primary structure of the allosteric L-lactate dehydrogenase from Lactobacillus casei. Eur J Biochem 1983;134:503-11.
[PUBMED] |
| 12. | Gallagher PG. Hemolytic anemias: Red cell membrane and metabolic defects. In: Goldman L, Schafer AI, editors. Cecil Medicine. 24 th ed. Philadelphia: Saunders Elsevier; 2011. p. 164.
|
| 13. | Crum-Cianflone NF. Immune reconstitution inflammatory syndromes: What's new? AIDS Read 2006;16:199-206.
[PUBMED] |
| 14. | National AIDS Control Organization 2008. HIV/AIDS Epidemiological Surveillance and Estimation Report. New Delhi: National AIDS Control Organization. Available from: http://www.aidsportal.org/repos/Fnlapil08rpt.pdf [Last accessed on 2012 Nov 2012].
|
| 15. | Valencia ME , Laguna F , Camacho J, Castejón A, Soriano V, Adrados M, et al. Serum activity of the lactate dehydrogenase enzyme in patients with human immunodeficiency virus infection. An Med Interna 1994;11:580-3.
|
| 16. | Butt AA , Michaels S, Kissinger P. The association of serum lactate dehydrogenase level with selected opportunistic infections and HIV progression. Int J Infect Dis 2002;6:178-81.
[PUBMED] |
| 17. | Vaccher E, Tirelli U, Spina M, Talamini R, Errante D, Simonelli C , et al. Age and serum lactate dehydrogenase level are independent prognostic factors in human immunodeficiency virus-related non-Hodgkin's lymphomas: A single-institute study of 96 patients. J Clin Oncol 1996;14:2217-23.
[PUBMED] |
| 18. | Silverman BA, Rubinstein A. Serum lactate dehydrogenase levels in adults and children with acquired immune deficiency syndrome (AIDS) and AIDS-related complex: Possible indicator of B cell lymphoproliferation and disease activity. Effect of intravenous gammaglobulin on enzyme levels. Am J Med 1985;78:728-36.
[PUBMED] |
| 19. | Peters EJ, Kauffmann RH, Blok P. Fever and high lactate dehydrogenase in HIV-positive patients from the Antilles and Surinam: Histoplasmosis? Neth J Med 2006;64:302-6.
[PUBMED] |
| 20. | Gutierrez ME, Canton A, Sosa N, Puga E, Talavera L. Disseminated histoplasmosis in patients with AIDS in Panama: A review of 104 cases. Clin Infect Dis 2005;40:1199-202.
[PUBMED] |
| 21. | Vogel M, Weissgerber P, Goeppert B, Hetzel J, Vatlach M, Claussen C, et al. Accuracy of serum LDH elevation for the diagnosis of Pneumocystis jiroveci pneumonia. Swiss Med Wkly 2011;141:w13184.
[PUBMED] |
| 22. | Quist J, Hill AR. Serum lactate dehydrogenase (LDH) in Pneumocystis carinii pneumonia, tuberculosis and bacterial pneumonia. Chest 1995;108:415-8.
[PUBMED] |
| 23. | UN AIDS Epidemicupdate 2007. Available from: http://data.unaids.org/pub/PressRelease/2007/070706_indiapressrelease_en.pdf [Last accessed on 2012 Nov 2012].
|
| 24. | Corcoran GR, Al-Abdely H, Flanders CD, Geimer J, Patterson TF. Markedly elevated serum lactate dehydrogenase levels are a clue to the diagnosis of disseminated histoplasmosis in patients with AIDS. Clin Infect Dis 1997;24:942-4.
[PUBMED] |
[Figure 1], [Figure 2]
[Table 1], [Table 2]
| This article has been cited by | | 1 |
Diffuse large B-cell lymphoma in a high human immunodeficiency virus (HIV) prevalence, low-resource setting |
|
| Pumza S. Magangane,Zainab Mohamed,Richard Naidoo | | South African Journal of Oncology. 2020; 4 | | [Pubmed] | [DOI] | | | 2 |
Regulation of lactate dehydrogenase in response to WSSV infection in the shrimp Litopenaeus vannamei |
|
| M.L.E. Hernández-Palomares,J.A. Godoy-Lugo,S. Gómez-Jiménez,L.A. Gámez-Alejo,R.M. Ortiz,J.F. Muñoz-Valle,A.B. Peregrino-Uriarte,G. Yepiz-Plascencia,J.A. Rosas-Rodríguez,J.G. Soñanez-Organis | | Fish & Shellfish Immunology. 2018; 74: 401 | | [Pubmed] | [DOI] | | | 3 |
Elevated lactate dehydrogenase (LDH) can be a marker of immune suppression in cancer: Interplay between hematologic and solid neoplastic clones and their microenvironments |
|
| Jennifer Ding,Judith E. Karp,Ashkan Emadi | | Cancer Biomarkers. 2017; : 1 | | [Pubmed] | [DOI] | | | 4 |
Association of HIV and highly active antiretroviral therapy with clinical and biochemical indices among women with pre-eclampsia |
|
| Niren R. Maharaj,Jagidesa Moodley,Anil Chuturgoon | | International Journal of Gynecology & Obstetrics. 2016; | | [Pubmed] | [DOI] | |
|
 |
|
|
|
Search Pubmed for