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Vol. 22, No. 1, 2013
Issue release date: December 2012
Section title: Original Paper
Open Access Gateway
Med Princ Pract 2013;22:54–58
(DOI:10.1159/000339201)

Relationship between Leptin Levels and Suppressed CD4 Counts in HIV Patients

Al-Fadhli M.b · Saraya M.a · Qasem J.c · Azizieh F.d · Shahab S.e · Raghupathy R.e
aDepartment of Tropical Medicine, Faculty of Medicine, Zagazig University, Zagazig City, Egypt; bDepartment of Medicine, Infectious Disease Hospital, Ministry of Health, Andalous, cDepartment of Applied Medical Sciences, College of Health Sciences, Public Authority for Applied Education and Training (PAAET), Shuwaik, dDepartment of Mathematics and Natural Sciences, Gulf University for Science and Technology, West Mishref, and eDepartment of Microbiology, Faculty of Medicine, Health Sciences Centre, Kuwait University, Jabriya, Kuwait
email Corresponding Author

Abstract

Objective: To examine the relationship between serum leptin levels and suppression of CD4 count in HIV-infected individuals with highly active antiretroviral therapy (HAART). Subjects and Methods: Thirty seropositive HIV male patients selected from the Infectious Disease Hospital were classified into two groups according to their immunological and virological response to HAART. The first group included 15 male patients with low viral load and low CD4 counts; the second included 15 male patients with low viral load and high CD4 counts. Morning serum leptin and tumor necrosis factor-α levels of HIV patients were measured and correlated with fasting serum insulin, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), HIV viral load and CD4 count. Results: Serum leptin levels were significantly higher in patients with high CD4 counts than in patients with low CD4 counts (mean serum leptin level 47.3 vs. 10.9 ng/ml, respectively; p < 0.0001). A positive correlation was observed between serum leptin levels and CD4 counts (r = 0.697; p < 0.0001); positive correlations were also seen between leptin levels and fasting serum insulin and HOMA-IR (r = 0.633, p < 0.0001, and r = 0.537, p < 0.003, respectively). Conclusion: Serum leptin level was higher in HIV patients with high CD4 count and correlated with fasting serum insulin and HOMA-IR, thereby indicating that HAART treatment could lead to decreased levels of leptin in HIV patients, which might lead to impaired immunological recovery.

© 2012 S. Karger AG, Basel


  

Key Words

  • Human immunodeficiency virus
  • CD4 T cells
  • Leptin
  • Highly active antiretroviral therapy

 Introduction

Leptin, a hormone synthesized mainly in adipose cells, is the 16-kDa nonglycosylated protein product of the obese (ob) gene [1]. It regulates body weight in a central manner via its cognate receptor in the hypothalamus [2]. Leptin is also expressed at lower levels in other tissues, such as the placenta and stomach [3]. There is increasing evidence that leptin has systemic effects apart from those related to energy homeostasis, including regulation of neuroendocrine, reproductive, hematopoietic and immune functions [4].

Obese (ob/ob) mice and leptin-deficient (ab/ab) mice, in which the leptin receptor is truncated, display immune dysfunction and lymphoid organ atrophy, affecting thymus size and cellularity, similar to that observed in starved animals and malnourished humans [5]. Thus, these mice have reduced levels of peripheral T and B cells, suggesting that leptin may have a role in lymphopoiesis. Leptin has been shown to protect mice from starvation-induced lymphoid atrophy and increases thymus cellularity in ob/ob mice [6]. Leptin also induces the proliferation, differentiation and functional activation of hematopoietic cells, and this function may explain the role of adipose tissue present in the marrow cavity [7].

Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome [8]. HIV primarily infects vital cells in the human immune system such as helper T cells (CD4+ T cells), macrophages and dendritic cells. HIV infection results in a reduction in levels of CD4+ T cells through three main mechanisms: direct viral killing of infected cells, increased rates of apoptosis of infected cells, and killing of infected CD4+ T cells by CD8+ cytotoxic T lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is impaired, and the body becomes progressively more susceptible to opportunistic infections [9].

Antiretroviral drugs keep the levels of HIV in the body at a low level, enabling the immune system to recover and work effectively. Highly active antiretroviral therapy (HAART) in HIV-1-infected individuals has a broad spectrum of clinical outcomes. In the majority of patients, the plasma viral load becomes undetectable and CD4+ T cells increase over time. However, in a number of subjects, a discrepancy between plasma viral load and CD4+ T-cell recovery has been observed. CD4+ T-cell count can rise despite persistently detectable plasma viral load (virologic nonresponders), which occurs in 7–15% of the patients [10], or conversely, CD4+ T- cell numbers do not increase despite plasma viral load suppression (immunologic nonresponders) [11]. It has been observed that 20% of patients receiving long-term HAART are ‘immunologic nonresponders’ [11], i.e. patients who fail to achieve a CD4+ T-cell count above 300 cells/µl at 6, 12, 18, 24 months of HAART [12]. Therefore, the aim of this study was to explore the role of serum leptin in the pathogenesis of suppression of CD4+ T-cell count in HIV patients despite a low viral load after HAART.

 

 Subjects and Methods

This study was conducted between December 2009 and March 2011 at the Infectious Disease Hospital, Kuwait, a tertiary care hospital that has been providing primary care to HIV-positive patients since 1990. The patients in this study were diagnosed as seropositive HIV 2 years prior to the study and were started on HAART, a combination of three or more anti-HIV medications from at least two different classes of nonnucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), or protease inhibitors. All subjects received the HAART regimen according to individual needs but there was no variation between the two groups as both groups were treated with similar classes of drug with regard to the HAART regimen. Of 148 patients who were on HAART for more than 2 years, 118 were excluded due to advanced age, female gender, higher or lower body mass index (BMI; lower BMI: <18.5; normal BMI: 18.5–24.9; higher BMI: 25–29.9), diabetic state, any opportunistic infections, coinfection with viral hepatitis, advanced stage of the disease or history of previous treatment interruption. This was intended to exclude factors that affect serum leptin levels. Thirty patients were selected and classified into two groups. The first group (group I) included 15 male patients with low viral load and low CD4 count; the second (group II) 15 male patients with low viral load and high CD4 count. All 30 patients were subjected to full history taking, thorough clinical examination, BMI (kg/m2), liver function test, kidney profile, complete blood count, fasting blood sugar, estimation of fasting serum insulin, estimation of the levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α; Beckman Coulter, France) and the anti-inflammatory cytokine interleukin-10 (IL-10, Beckman Coulter, France), and estimation of morning serum leptin (Diagnostic Systems Laboratories, USA) using enzyme-linked immunosorbent assay. Calculation of Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was performed using the following equation: fasting plasma insulin (µU/ml) × fasting plasma glucose (mmol/l)/22.5, which is highly correlated with insulin resistance [13].

 Statistical Analysis

Data were first tested by One-Sample Kolmogorov-Smirnov Normality Test and subsequently analyzed with respective parametric or nonparametric tests. Comparisons between the groups were made using independent Student’s t test for parametric variables and by Mann-Whitney U test for nonparametric variables. Pearson’s correlation and Spearman rank correlation were used to measure association between quantitative data whether parametric or nonparametric; p value was considered significant if it was less than 0.05.

 

 Results

The age and BMI of the patients in both the low viral/CD4 count and low viral/high CD4 count groups were compared, no statistically significant differences in the means in regard to age (p < 0.66) and BMI (p < 0.29) between the groups were observed (table 1). For all patients in both groups, there were no morphological changes in the body due to HIV lipodystrophy, nor was there any disruption of normal eating patterns or any changes in BMI from the time the HAART regimen was initiated until the endpoint of the study. CD4 counts in group I (238 cells/µl) were significantly lower compared to those in group II (691 cells/µl, p < 0.0001). Group I also had a significantly lower viral load than group II. Leptin levels were significantly higher in group II (47.3 ng/ml) than in group I (10.9 ng/ml, p < 0.0001). While fasting serum insulin levels were significantly different, there was no significant difference in HOMA-IR (table 1). A positive correlation was observed between leptin levels and CD4 counts (r = 0.697, p < 0.0001; table 2). Similarly, there was a positive correlation between leptin levels and insulin (r = 0.633, p < 0.0001) as well as between leptin levels and HOMA-IR (r = 0.537, p < 0.003).

TAB01
Table 1. Comparison of age, BMI, serum leptin, serum insulin, HOMA-IR, TNF-α, CD4 counts and viral load in groups I and II

TAB02
Table 2. Correlation between serum leptin levels and TNF-α and other parameters in study groups

With regard to serum cytokine levels, there were significantly higher levels of the proinflammatory cytokine TNF-α in group I (p < 0.045); the TNF-α/IL-10 ratio was higher in group I than in group II (p < 0.042), suggestive of a stronger proinflammatory bias in group I. Furthermore, there was a significant negative correlation between the TNF-α and the CD4 counts (r = –0.410, p value 0.027; table 2). No significant correlations were observed between leptin levels and age, BMI, viral loads and serum levels of TNF-α or IL-10.

 

 Discussion

Our results showed no significant difference in HOMA-IR between group I and group II; fasting glucose levels were normal in all subjects, presumably because all diabetic patients were excluded from the study. Nevertheless, it is relevant to note that patients with insulin resistance tend to remain euglycemic as long as there is an adequate compensatory increase in insulin output from the pancreas. Impaired glucose tolerance and diabetes ensue when the level of insulin resistance exceeds the compensatory increase in pancreatic insulin output. However, insulin resistance has been widely reported to occur among HIV-infected patients [14,15]. It has been suggested that several factors may contribute to the risk of developing IR in these subjects, including type and duration of antiretroviral agents, severity and duration of HIV infection, undetectable viral load, age, weight, BMI, HCV infection, and lipid abnormalities [16], but the small sample size of our study could have limited the power to detect factors related to impairment of glucose homeostasis.

Insulin resistance appeared to be a consistent feature in the HIV patients of this study, especially in group II. There are three possible explanations: first, protease inhibitor drugs were used as a constituent of HAART and some of these drugs directly bound to and blocked the insulin-sensitive glucose transporter (GLUT 4), thus inhibiting glucose transport [17,18]. This effect, which has been demonstrated in both adipocytes and myocytes, induces peripheral insulin resistance in skeletal muscle and adipose tissue and impairs the ability of beta cells to compensate [19]. Second, protease inhibitors vary in their ability to induce insulin resistance. Our subjects were not randomly assigned to receive different types of therapy or protease inhibitors. Therefore, we could not demonstrate an association between the use of protease inhibitors and the development of insulin resistance. Third, HIV itself has been linked to insulin resistance [20]. While there is ongoing debate on the role of HIV in adipose tissue inflammation, the ability of the virus to modify adipocyte phenotype has been demonstrated in a study by Sankalé et al. [21]. Moreover, infected macrophages in lipodystrophic adipose tissue show modified characteristics. When activated, these cells secrete proinflammatory cytokines such as TNF-α and IL-6 that control adipocyte metabolism, decrease adiponectin production and induce insulin resistance and lipolysis [22]. This concept, called lipotoxicity, may explain why chronic HIV disease is associated with abnormal metabolic changes including insulin resistance and dyslipidemia in the absence of antiretroviral drugs [23].

An interesting feature of this study is the finding of a significant difference in the levels of the proinflammatory cytokine TNF-α between the two groups (table 1), which is in agreement with Resino et al. [24], who found higher levels of TNF-α at lower HIV viral loads. Another report by Hestdal et al. [25] describes higher levels of serum TNF-α in HIV patients with lower CD4+ counts. This is in accord with our observation of elevated TNF-α levels in subjects with decreased CD4 counts. A plausible explanation for high TNF-α levels in subjects with low CD4 counts is that the increased TNF-α may have been produced by other cells such as CD8+ T cells, the levels of which may have been elevated in these subjects. The ratio of TNF-α to IL-10 is higher in group I, i.e. patients with a lower CD4 and lower viral load. That is, the Th1/Th2 cytokine ratio is higher in this group, again suggestive of a CD8+ T cell predominance in these subjects.

TNF-α levels did not correlate with HOMA-IR and fasting insulin levels in both groups (table 2), suggesting but not unequivocally confirming that TNF-α does not have a significant role in the pathogenesis of insulin resistance. Yet another mechanistic explanation of insulin resistance in HIV patients is that NRTIs may contribute to insulin resistance, usually indirectly through metabolic changes and fat redistribution [26]. Oxidative stress and/or mitochondrial insult from NRTI exposure may represent a common pathway for increased lactate levels and decreased adiponectin from adipocytes, which ultimately result in insulin resistance in patients with HIV infection who are receiving antiretroviral therapy [27].

In this study, the serum leptin concentration was positively correlated with HOMA-IR, which reflects the degree of insulin resistance and concentration of serum insulin. Our results are similar to other studies [28], which describe an important role for insulin in the state of hyperleptinemia. Compensatory hyperinsulinemia due to insulin resistance stimulates adipocytes to produce leptin [29]. We hypothesized that the hyperleptinemia in group II was due to hyperinsulinemia. Although it has been reported that proinflammatory cytokines such as TNF-α induce production of leptin from adipocytes [30], a significant correlation between serum leptin levels and TNF-α in both groups was not found, suggesting that TNF-α did not play a role in hyperleptinemia in group II.

Despite the fact that virological suppression was better in group I than in group II, the CD4 counts in group II were higher than in group I (table 1). In addition, a clear positive correlation between serum leptin levels and CD4 counts (table 2) was found, supporting the assumption that the hyperleptinemia in group II had an important role in improving CD4 counts in HIV patients.

 

 Conclusion

Serum leptin level was higher in HIV patients with high CD4 count and correlated with fasting serum insulin and HOMA-IR, thereby indicating that HAART treatment could lead to decreased levels of leptin in HIV patients, which might lead to impaired immunological recovery.


References

  1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425–432.
  2. Sánchez-Pozo C, Rodriguez-Baño J, Domínguez-Castellano A, Muniain MA, Goberna R, Sánchez-Margalet V: Leptin stimulates the oxidative burst in control monocytes but attenuates the oxidative burst in monocytes from HIV-infected patients. Clin Exp Immunol 2003;134:464–469.
  3. Masuzaki H, Ogawa Y, Sagawa N, Hosoda K, Matsumoto T, Mise H, Nishimura H, Yoshimasa Y, Tanaka I, Mori T, Nakao K: Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med 1997;3:1029–1033.
  4. Fernández-Riejos P, Najib S, Santos-Alvarez J, Martín-Romero C, Pérez-Pérez A, González-Yanes C, Sánchez-Margalet V: Role of leptin in the activation of immune cells. Mediators Inflamm 2010;2010:568343.
  5. Palacio A, Lopez M, Perez-Bravo F, Monkeberg F, Schlesinger L: Leptin levels are associated with immune response in malnourished infants. J Clin Endocrinol Metab 2002;87:3040–3046.
  6. Claycombe K, King LE, Fraker PJ: A role for leptin in sustaining lymphopoiesis and myelopoiesis. Proc Natl Acad Sci USA 2008;105:2017–2021.
  7. Faggioni R, Jones-Carson J, Reed DA, Dinarello CA, Feingold KR, Grunfeld C, Fantuzzi G: Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity. Role of tumor necrosis factor alpha and IL-18. Proc Natl Acad Sci USA 2000;97:2367–2372.
  8. Migueles S, Connors M: Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. JAMA 2010;304:194–201.
  9. Douek DC, Roederer M, Koup RA: Emerging concepts in the immunopathogenesis of AIDS. Annu Rev Med 2009;60:471–484.
  10. Fessel WJ, Krowka JF, Sheppard HW, Gesner M, Tongson S, Weinstein S, Ascher M, Kwok S, Christopherson C: Dissociation of immunologic and virologic responses to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2000;23:314–320.
  11. Tan R, Westfall AO, Willig JH, Mugavero MJ, Saag MS, Kaslow RA, Kempf MC: Clinical outcome of HIV-infected antiretroviral-naive patients with discordant immunologic and virologic responses to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2008;47:553–558.
  12. Aiuti F, Mezzaroma I: Failure to reconstitute CD4+ T-cells despite suppression of HIV replication under HAART. AIDS Rev 2006;8:88–97.
  13. Methews DR, Hos Ker JP, Rudenski AS, Naylor BA, Treacher OF, Turner RC: Homeostasis modal assessment insulin resistance and B cell function from fasting plasma glucose and insulin concentration in man. Diabetologia 1985;23:412–419.

    External Resources

  14. Panos G, Samonis G, Alexiou VG, Kavarnou GA, Charatsis G, Falagas ME: Mortality and morbidity of HIV infected patients receiving HAART: a cohort study. Curr HIV Res 2008;6:257–264.
  15. Bitnun A, Sochett E, Babyn P, Holowka S, Stephens D, Read S, King SM: Serum lipids, glucose homeostasis and abdominal adipose tissue distribution in protease inhibitor-treated and naïve HIV-infected children. AIDS 2003;17:1319–1327.
  16. Wanke CA, Falutz JM, Shevitz A, Phair JP, Kotler DP: Clinical evaluation and management of metabolic and morphologic abnormalities associated with human immunodeficiency virus. Clin Infect Dis 2002;34:248–259.
  17. Hruz PW: Molecular mechanisms for altered glucose homeostasis in HIV infection. Am J Infect Dis 2006;2:187–192.
  18. Lee GA, Rao MN, Grunfeld C: The effects of HIV protease inhibitors on carbohydrate and lipid metabolism. Curr HIV/AIDS Rep 2005;2:39–50.
  19. Woerle HJ, Mariuz PR, Meyer C, Reichman RC, Popa EM, Dostou JM, Welle SL, Gerich JE: Mechanisms for the deterioration in glucose intolerance associated with HIV protease inhibitor regimen. Diabetes 2003;52:918–925.
  20. Capeau J: From lipodystrophy and insulin resistance to metabolic syndrome: HIV infection, treatment and aging. Curr Opin HIV AIDS 2007;2:247–252.
  21. Sankalé JL, Tong Q, Hadigan CM, Tan G, Grinspoon SK, Kanki PJ, Hotamisligil GS: Regulation of adiponectin in adipocytes upon exposure to HIV-1. HIV Med 2006;7:268–274.
  22. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr: Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796–1808.
  23. Meininger G, Hadigan C, Laposata M, Brown J, Rabe J, Louca J, Aliabadi N, Grinspoon S: Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution. Metabolism 2000;51:260–266.
  24. Resino S, Jiménez JL, Bellón JM, Gurbindo D, Muñoz-Fernández MA: Correlation between high plasma viral load and levels of TNF-alpha and cICAM-1 in HIV-1 infected children. An Esp Pediatr 2000;52:501–506.
  25. Hestdal K, Aukrust P, Müller F, Lien E, Bjerkeli V, Espevik T, Frøland S: Dysregulation of membrane-bound tumor necrosis factor-α and tumor necrosis factor receptors on mononuclear cells in human immunodeficiency virus type 1 infection: low percentage of p75-tumor necrosis factor receptor positive cells in patients with advanced disease and high viral load. Blood 1997;90:2670–2679.
  26. Shlay JC, Bartsch G, Peng G, Wang J, Grunfeld C, Gibert CL, Visnegarwala F, Raghavan SS, Xiang Y, Farrough M, Perry HE, Kotler D, El-Sadr WM: Long-term body composition and metabolic changes in antiretroviral naïve persons randomized to protease inhibitor, non-nucleoside reverse transcriptase inhibitor or protease inhibitor plus non-nucleoside reverse transcriptase strategy. J Acquir Immune Defic Syndr 2007;44:506–517.
  27. Soares AF, Guichardant M, Cozzone D, Bernoud-Hubac N, Bouzaïdi-Tiali N, Lagarde M, Géloën A: Effects of oxidative stress on adiponectin secretion and lactate production in 3T3-L1 adipocytes. Free Radic Biol Med 2005;38:882–889.
  28. Oncul O, Top C, Cavuslu T: Correlation of serum leptin levels with insulin sensitivity in patients with chronic hepatitis C infection. Diabetes Care 2002;25:937.
  29. Boden G, Chen X, Kolaczynski JW, Polansky M: Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects. J Clin Invest 1997;100:1107–1113.
  30. Simons PJ, van den Pangaart PS, van Roomen CP, Aerts JM, Boon L: Cytokine-mediated modulation of leptin and adiponectin secretion during in vitro adipogenesis: evidence that tumor necrosis factor-alpha- and interleukin-1beta-treated human preadipocytes are potent leptin producers. Cytokine 2005;32:94–103.

  

Author Contacts

Dr. Mariam Al-Fadhli
Al-Andalus, Area 6, Street 102
House No. 275
Kuwait
Tel. +965 9966 0936, E-Mail medicine209@gmail.com

  

Article Information

Received: July 7, 2011
Accepted: April 25, 2012
Published online: June 21, 2012
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 2, Number of References : 30

  

Publication Details

Medical Principles and Practice (International Journal of the Kuwait University Health Sciences Centre)

Vol. 22, No. 1, Year 2013 (Cover Date: December 2012)

Journal Editor: Owunwanne A. (Kuwait), Benov L. (Kuwait)
ISSN: 1011-7571 (Print), eISSN: 1423-0151 (Online)

For additional information: http://www.karger.com/MPP


Open Access License / Drug Dosage / Disclaimer

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Objective: To examine the relationship between serum leptin levels and suppression of CD4 count in HIV-infected individuals with highly active antiretroviral therapy (HAART). Subjects and Methods: Thirty seropositive HIV male patients selected from the Infectious Disease Hospital were classified into two groups according to their immunological and virological response to HAART. The first group included 15 male patients with low viral load and low CD4 counts; the second included 15 male patients with low viral load and high CD4 counts. Morning serum leptin and tumor necrosis factor-α levels of HIV patients were measured and correlated with fasting serum insulin, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), HIV viral load and CD4 count. Results: Serum leptin levels were significantly higher in patients with high CD4 counts than in patients with low CD4 counts (mean serum leptin level 47.3 vs. 10.9 ng/ml, respectively; p < 0.0001). A positive correlation was observed between serum leptin levels and CD4 counts (r = 0.697; p < 0.0001); positive correlations were also seen between leptin levels and fasting serum insulin and HOMA-IR (r = 0.633, p < 0.0001, and r = 0.537, p < 0.003, respectively). Conclusion: Serum leptin level was higher in HIV patients with high CD4 count and correlated with fasting serum insulin and HOMA-IR, thereby indicating that HAART treatment could lead to decreased levels of leptin in HIV patients, which might lead to impaired immunological recovery.

© 2012 S. Karger AG, Basel


  

Author Contacts

Dr. Mariam Al-Fadhli
Al-Andalus, Area 6, Street 102
House No. 275
Kuwait
Tel. +965 9966 0936, E-Mail medicine209@gmail.com

  

Article Information

Received: July 7, 2011
Accepted: April 25, 2012
Published online: June 21, 2012
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 2, Number of References : 30

  

Publication Details

Medical Principles and Practice (International Journal of the Kuwait University Health Sciences Centre)

Vol. 22, No. 1, Year 2013 (Cover Date: December 2012)

Journal Editor: Owunwanne A. (Kuwait), Benov L. (Kuwait)
ISSN: 1011-7571 (Print), eISSN: 1423-0151 (Online)

For additional information: http://www.karger.com/MPP


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 7/7/2011 10:10:44 AM
Accepted: 4/25/2012
Published online: 6/21/2012
Issue release date: December 2012

Number of Print Pages: 5
Number of Figures: 0
Number of Tables: 2

ISSN: 1011-7571 (Print)
eISSN: 1423-0151 (Online)

For additional information: http://www.karger.com/MPP


Open Access License / Drug Dosage

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425–432.
  2. Sánchez-Pozo C, Rodriguez-Baño J, Domínguez-Castellano A, Muniain MA, Goberna R, Sánchez-Margalet V: Leptin stimulates the oxidative burst in control monocytes but attenuates the oxidative burst in monocytes from HIV-infected patients. Clin Exp Immunol 2003;134:464–469.
  3. Masuzaki H, Ogawa Y, Sagawa N, Hosoda K, Matsumoto T, Mise H, Nishimura H, Yoshimasa Y, Tanaka I, Mori T, Nakao K: Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med 1997;3:1029–1033.
  4. Fernández-Riejos P, Najib S, Santos-Alvarez J, Martín-Romero C, Pérez-Pérez A, González-Yanes C, Sánchez-Margalet V: Role of leptin in the activation of immune cells. Mediators Inflamm 2010;2010:568343.
  5. Palacio A, Lopez M, Perez-Bravo F, Monkeberg F, Schlesinger L: Leptin levels are associated with immune response in malnourished infants. J Clin Endocrinol Metab 2002;87:3040–3046.
  6. Claycombe K, King LE, Fraker PJ: A role for leptin in sustaining lymphopoiesis and myelopoiesis. Proc Natl Acad Sci USA 2008;105:2017–2021.
  7. Faggioni R, Jones-Carson J, Reed DA, Dinarello CA, Feingold KR, Grunfeld C, Fantuzzi G: Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity. Role of tumor necrosis factor alpha and IL-18. Proc Natl Acad Sci USA 2000;97:2367–2372.
  8. Migueles S, Connors M: Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. JAMA 2010;304:194–201.
  9. Douek DC, Roederer M, Koup RA: Emerging concepts in the immunopathogenesis of AIDS. Annu Rev Med 2009;60:471–484.
  10. Fessel WJ, Krowka JF, Sheppard HW, Gesner M, Tongson S, Weinstein S, Ascher M, Kwok S, Christopherson C: Dissociation of immunologic and virologic responses to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2000;23:314–320.
  11. Tan R, Westfall AO, Willig JH, Mugavero MJ, Saag MS, Kaslow RA, Kempf MC: Clinical outcome of HIV-infected antiretroviral-naive patients with discordant immunologic and virologic responses to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2008;47:553–558.
  12. Aiuti F, Mezzaroma I: Failure to reconstitute CD4+ T-cells despite suppression of HIV replication under HAART. AIDS Rev 2006;8:88–97.
  13. Methews DR, Hos Ker JP, Rudenski AS, Naylor BA, Treacher OF, Turner RC: Homeostasis modal assessment insulin resistance and B cell function from fasting plasma glucose and insulin concentration in man. Diabetologia 1985;23:412–419.

    External Resources

  14. Panos G, Samonis G, Alexiou VG, Kavarnou GA, Charatsis G, Falagas ME: Mortality and morbidity of HIV infected patients receiving HAART: a cohort study. Curr HIV Res 2008;6:257–264.
  15. Bitnun A, Sochett E, Babyn P, Holowka S, Stephens D, Read S, King SM: Serum lipids, glucose homeostasis and abdominal adipose tissue distribution in protease inhibitor-treated and naïve HIV-infected children. AIDS 2003;17:1319–1327.
  16. Wanke CA, Falutz JM, Shevitz A, Phair JP, Kotler DP: Clinical evaluation and management of metabolic and morphologic abnormalities associated with human immunodeficiency virus. Clin Infect Dis 2002;34:248–259.
  17. Hruz PW: Molecular mechanisms for altered glucose homeostasis in HIV infection. Am J Infect Dis 2006;2:187–192.
  18. Lee GA, Rao MN, Grunfeld C: The effects of HIV protease inhibitors on carbohydrate and lipid metabolism. Curr HIV/AIDS Rep 2005;2:39–50.
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