Low humoral responses to human cytomegalovirus is associated with immunological treatment failure among HIV infected patients on highly active antiretroviral therapy
Mariam Mwinjuma Mirambo, Ndealilia Senyaeli, Stephen Eliatosha Mshana
The Pan African Medical Journal. 2017;28:131. doi:10.11604/pamj.2017.28.131.10480

Create an account  |  Sign in
Case studies in Public health Supplement 2 Supplement
"Better health through knowledge sharing and information dissemination "

Brief

Low humoral responses to human cytomegalovirus is associated with immunological treatment failure among HIV infected patients on highly active antiretroviral therapy

Cite this: The Pan African Medical Journal. 2017;28:131. doi:10.11604/pamj.2017.28.131.10480

Received: 04/08/2016 - Accepted: 07/06/2017 - Published: 10/10/2017

Key words: IgG, HCMV, HIV, immunological failure

© Mariam Mwinjuma Mirambo et al. The Pan African Medical Journal - ISSN 1937-8688. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Available online at: http://www.panafrican-med-journal.com/content/article/28/131/full

Corresponding author: Mariam Mirambo, Department of Microbiology and Immunology, Weill Bugando School of Medicine, P.O. Box 1464, Mwanza, Tanzania (mmmirambo@gmail.com)


Low humoral responses to human cytomegalovirus is associated with immunological treatment failure among HIV infected patients on highly active antiretroviral therapy

Mariam Mwinjuma Mirambo1,&, Ndealilia Senyaeli1, Stephen Eliatosha Mshana1

 

1Department of Microbiology and Immunology, Weill Bugando School of Medicine, P.O. Box 1464, Mwanza, Tanzania

 

 

&Corresponding author
Mariam Mirambo, Department of Microbiology and Immunology, Weill Bugando School of Medicine, P.O. Box 1464, Mwanza, Tanzania

 

 

Abstract

Human cytomegalovirus (HCMV) is one of the opportunistic infections associated with significant morbidity and mortality among HIV/AIDS patients especially before introduction of antiretroviral therapy (ART). Little is known regarding the humoral immune response against HCMV in relation to CD4 counts among HIV infected individuals. A total of 90 achieved sera from HIV infected patients attending Bugando Medical centre care and treatment centre (CTC) aged 18 years and above were retrieved and analyzed. Sociodemographic data were collected using structured data collection tool. Detection of specific HCMV antibodies was done using Indirect Enzyme Linked Immunosorbent Assay (ELISA). Data were analyzed by using STATA version 11. A total of 90 HIV infected patients were enrolled in the study whereby 36(40%) had immunological treatment failure. The mean age of the study participants was 39±12.3 years. The Prevalence of specific HCMV IgG antibodies was 84(93.3%, 95% CI: 88-98.5) while the prevalence of specific HCMV IgM antibodies was 2(2.3% 95% CI: 0.8-5.4). The median CD4 counts at 6 months and 12 months on HAART were significantly high in treatment success group. At 12 months of HAART as CD4 counts increases the HCMV IgG index value was also found to increase significantly, p=0.04. Significant proportion of HIV infected individuals was infected with HCMV. Higher median HCMV IgG titers were observed among patients with immunological treatment success. There is a need to investigate humoral immune responses in HIV infected individuals in relation to CD4 counts against various infectious diseases in developing countries where most of these infections are endemic.

 

 

Brief Up    Down

Human cytomegalovirus (HCMV) has been known to establish latency following primary subclinical infections in immunocompetent individuals [1, 2]. In these individuals reactivation may occur periodically without any observed sequels. However, in deficiency of host-derived antiviral immune responses reactivation often cause pathological changes that may results into invasive disease [3-5]. Long-lasting immunity in response to HCMV primary infection serves to control subsequent HCMV reactivation in the host which is essential for preventing uncontrolled viral replication and serious HCMV disease [6]. In this context humoral and cell mediated immunity plays a crucial role in sustaining the balance between maintenance and reactivation which may results into pathological changes among these patients in case of any disruption. Human immunodeficiency virus (HIV) infected patients can control this balance when they start therapy as the CD4 counts and other immunological markers increases. However, in patients with immunological treatment failure it has been hypothesized that low CD4 counts may indicate failure of immune system to mount immunological responses to various antigens including latent HCMV or new infections [7-9]. Whether immunological treatment failure can affect generation of antibody responses to HCMV in these patients or not has never been established. This study investigated the specific HCMV IgG titers values in relation to CD4 counts as a marker of immunological treatment failure among HIV patients on highly active antiretroviral therapy (HAART).

 

A total of 90 achieved sera from HIV infected patients attending Bugando Medical centre CTC aged above 18 years were retrieved and analyzed. The sera were obtained at 12 months of HAART. Sociodemographic and other relevant information were obtained from patients' records. Detection of specific HCMV IgG antibodies was done using commercial indirect enzyme-linked immunosorbent assay (PishtazTeb, Tehran, Iran) according to manufacturer's instructions [10-13]. Data analysis was done by using STATA version 11. Proportions and confidence intervals were determined. Two-sample Wilcoxon rank-sum (Mann-Whitney) test was done to compare median CD4 counts among participants with immunological treatment failure and those with immunological treatment success. Scatter diagrams were drawn using patients CD4 counts records at baseline, at 6 months and 12months in relation to HCMV IgG index values. Regression analysis was done to determine the statistical significance of the correlation. The protocol to conduct the study obtained waiver of consent from the Joint Catholic University of Health and Allied Sciences/Bugando Medical Centre (CUHAS/BMC) research ethics and review committee with clearance number CREC.208/2016. Of 90 HIV infected patient's sera, 36(40%) were from patients who had immunological treatment failure. The mean age of the study participants was 39±12.3 years. Majority of participants were male 61(67.8%) and those with primary education were 63(70%). Regarding marital status, unmarried individuals formed majority 61(67.8%) of the study participants. In addition 54(59.9%) of the participants were employed.

 

A total of 84(93.3%, 95% CI: 88-98.5) sera had specific HCMV IgG antibodies while only 2(2.3% 95% CI: 0.8-5.4) had specific HCMV IgM antibodies. Higher rates of HCMV IgG seroprevalence have been similarly observed elsewhere among HIV infected individuals [14, 15]. In comparison to previous studies the reported prevalence of HCMV IgM antibodies was lower [16]. As per WHO citeria [17], the median CD4 counts were significantly higher among patients who had immunological treatment success at 6 months and 12 months (Table 1). On the regression analysis there was no significant correlation between baseline CD4 counts and HCMV IgG index value (p=0.45). This could be due to sigfnificant low CD4 counts which might have contributed to the impared function of CD4 due to high viral load [17, 18]. Correlation with bordeline significant between CD4 counts and HCMV IgG index values was oberved at 6 months on HAART while significant correlation between CD4 counts and HCMV IgG index value was observed at 12 months on HAART, p=0.04, (Figure 1). Generally we observed that at 6 months and 12 months there was significant relation between IgG titers and CD4 counts in the treatment success group. This could be due to increase immunocompetency which is associated with HAART treatment. Previous study [19] showed that the increase in CD4 count and function is associated with increased humoral response. In addition no significant difference was observed on the HCMV antibody titers in relation to age in both groups, signifying that HIV and CD4 counts are only factors influencing HCMV humoral immune responses.

 

In conclusion significant proportion of HIV infected individuals were HCMV IgG sero-positive and the HCMV IgG titers significantly increased as CD4 counts increases. Further studies to investigate the humoral immune response in HIV infected individuals in relation to CD4 counts against various infectious diseases are warranted in developing countries.

 

 

Competing interests    Down

The authors declares that they have no competing interests.

 

 

Authors’ contributions Up    Down

Mariam Mwinjuma Mirambo and Stephen Eliatosha Mshana participated in the design of the work. NS performed laboratory tests. Mariam Mwinjuma Mirambo, NdealiliaSenyaeli and Stephen Eliatosha Mshana analyzed and interpreted the data. Mariam Mwinjuma Mirambo and Stephen Eliatosha Mshana wrote the first draft of the manuscript. All authors read and approved the final version of the manuscript.

 

 

Acknowledgments Up    Down

The authors would like to acknowledge the technical support provided by Mr Vitus Silago, all staff at Bugando medical centre (BMC) with special thanks to Dr. Hyasinta Jaka. This study was supported by research grant from CUHAS

 

 

Table and figure Up    Down

Table 1: median CD4 counts in relation to treatment status of HCMV IgG positive

Figure 1: HCMV index value of HIV infected individuals in relation to CD4 counts at baseline, 6 months, 12 months. TF: Treatment Failure, TS: Treatment Success

 

 

References Up    Down

  1. La Rosa C, Diamond DJ. The immune response to human CMV. Future virol. 2012; 7(3):279-293. PubMed | Google Scholar

  2. Gamadia LE, Remmerswaal EB, Weel JF, Bemelman F, van Lier RA, Ten Berge IJ. Primary immune responses to human CMV: a critical role for IFN-γ-producing CD4+ T cells in protection against CMV disease. Blood. 2003; 101(7):2686-2692. PubMed | Google Scholar

  3. Crough T, Khanna R. Immunobiology of human cytomegalovirus: from bench to bedside. Clin Microbiol Rev. 2009; 22(1):76-98. PubMed | Google Scholar

  4. Steininger C. Clinical relevance of cytomegalovirus infection in patients with disorders of the immune system. Clin Microbiol Infect. 2007; 13(10):953-963. PubMed | Google Scholar

  5. Limaye AP, Bakthavatsalam R, Kim HW, Randolph SE, Halldorson JB, Healey PJ, Kuhr CS, Levy AE, Perkins JD, Reyes JD. Impact of cytomegalovirus in organ transplant recipients in the era of antiviral prophylaxis. Transplantation. 2006; 81(12):1645-1652. PubMed | Google Scholar

  6. Northfield JW, Harcourt G, Lucas M, Klenerman P. Immunology of viral co-infections with HIV. Arch Immunol Ther Exp. 2005; 53(1):3-12. PubMed | Google Scholar

  7. Lawrence J, Mayers DL, Hullsiek KH, Collins G, Abrams DI, Reisler RB, Crane LR, Schmetter BS, Dionne TJ, Saldanha JM. Structured treatment interruption in patients with multidrug-resistant human immunodeficiency virus. N Engl J Med. 2003; 349(9):837-846. PubMed | Google Scholar

  8. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, Fätkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, Losso M, Markowitz N, Neuhaus J, Phillips A, Rappoport C. CD4+ count–guided interruption of antiretroviral treatment. N Engl J Med. 2006; 2006(355):2283-2296. PubMed | Google Scholar

  9. Torriani FJ, Freeman WR, Macdonald JC, Karavellas MP, Durand DM, Jeffrey DD, Meylan PR, Schrier RD. CMV retinitis recurs after stopping treatment in virological and immunological failures of potent antiretroviral therapy. AIDS. 2000; 14(2):173-180. PubMed | Google Scholar

  10. Souza VAUFd, Sumita LM, Otsubo MES, Takei K, Pannuti CS. Enzyme linked immunosorbent assay for rubella antibodies, a simple method of antigen production: a preliminary report. Rev Inst Med Trop São Paulo. 1995; 37(4):357-359. Google Scholar

  11. Field P, Ho D, Cunningham A. Evaluation of rubella immune status by three commercial enzyme-linked immunosorbent assays. J Clin Microbiol. 1988;26(5):990-994. PubMed | Google Scholar

  12. Chernesky M, Wyman L, Mahony J, Castriciano S, Unger J, Safford J, Metzel P. Clinical evaluation of the sensitivity and specificity of a commercially available enzyme immunoassay for detection of rubella virus-specific immunoglobulin M. J Clin Microbiol. 1984, 20(3):400-404. PubMed | Google Scholar

  13. Schwarz TF, Jäger G, Gilch S. Comparison of seven commercial tests for the detection of parvovirus B19-specific IgM. Zentralblatt für Bakteriologie. 1997; 285(4):525-530. PubMed | Google Scholar

  14. Fowotade A, Okonko IO, Agbede OO, Suleiman S. High seropositivity of IgG and IgM antibodies against cytomegalovirus (CMV) among HIV-1 seropositive patients in Ilorin, Nigeria. Afr Health Sci. 2015; 15(1):1-9. PubMed | Google Scholar

  15. Kida IM, Denue BA, Bakki B, Waru BG, Talle MA, Ummate I, Kwayabura SA, Kuburi IS, Yusuph H. Seroprevalence of and Risk Factors for Cytomegalovirus among HIV-Infected Patients at University of Maiduguri Teaching Hospital, Nigeria. OJI. 2014; 4(2):54-59. Google Scholar

  16. Ojide C, Kalu E, Nwadike V, Ogbaini-Emovon E, Omoti C. Seroprevalence of Cytomegalovirus among HIV-Infected Adult Patients on HAART. IJTDH.2016; 17(3):1-6. Google Scholar

  17. WHO. WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. 2007. Google Scholar

  18. Dragsted UB, Mocroft A, Vella S, Viard J-P, Hansen A-BE, Panos G, Mercey D, Machala L, Horban H, Lundgren JD. Predictors of immunological failure after initial response to highly active antiretroviral therapy in HIV-1-infected adults: a EuroSIDA study. Jof Infect Dis. 2004; 190(1):148-155. PubMed | Google Scholar

  19. Arias RA, Moro-García M, Echeverría A, Solano-Jaurrieta J, Suárez-García F, López-Larrea C. Intensity of the humoral response to cytomegalovirus is associated with the phenotypic and functional status of the immune system. J of Virol. 2013;87(8):4486-4495. PubMed | Google Scholar

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


The Pan African Medical Journal articles are archived on Pubmed Central. Access PAMJ archives on PMC here

Volume 28 (September - December 2017)

Article tools

PDF in process
Log in to comment
Contact the corresponding author
Download to Citation Manager
EndNote
Reference Manager
Zotero
BibTex
ProCite


Rate this article

Altmetric

PAMJ is a member of the Committee on Publication Ethics
Next abstract

PAMJ is published in collaboration with the African Field Epidemiology Network (AFENET)
Currently tracked by: DOAJ, AIM, Google Scholar, AJOL, EBSCO, Scopus, Embase, IC, HINARI, Global Health, PubMed Central, PubMed/Medline, Ulrichsweb, More to come . Member of COPE.

ISSN: 1937-8688. © 2017 - Pan African Medical Journal. All rights reserved