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Current HIV Research

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ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

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Letter Article

A TNF Block Genotype may Influence CMV Retinitis in HIV Patients without Affecting Systemic Viral Replication

Author(s): Lukman Edwar, Phuongnhi Ha, Ibnu A. Ariyanto, Riwanti Estiasari, Ratna Sitompul, Silvia Lee and Patricia Price*

Volume 19, Issue 1, 2021

Published on: 10 September, 2020

Page: [96 - 99] Pages: 4

DOI: 10.2174/1570162X18666200910151050

Price: $65

Abstract

Background: A conserved TNF block haplotype marked by the minor alleles of rs1800629 (TNFA-308*A) and rs9281523 [BAT1(intron 10)*C] has been linked with several immunopathological conditions and with rapid progression of HIV disease. Reported associations with cytomegalovirus (CMV) retinitis in HIV patients before or during early antiretroviral therapy (ART) may therefore reflect greater replication of CMV in advanced HIV disease or an immunopathological response to CMV in the retina.

Objective: As all Indonesian HIV patients display high levels of CMV replication, we evaluated whether TNF block genotypes alter markers of their burden of CMV and/or associate with retinitis.

Methods: We assessed 79 consecutive HIV patients beginning ART, 25 HIV patients with a history of CMV-retinitis and 63 healthy adults. HIV RNA, CD4 T-cell counts, CMV-reactive antibody and CMV DNA were measured and alleles of TNFA-308, BAT1(intron 10) and TNFA-1031 (rs1799964) were determined.

Results: TNFA-308 and BAT1(intron 10) were in complete linkage disequilibrium. Patients carrying minor alleles at both loci had higher levels of CMV-reactive antibody after one month on ART (p=0.01), but not at other time points spanning 1 year on ART. 50% of patients had detectable CMV DNA before ART, irrespective of TNF block genotypes. However, the TNFA-308*A/- BAT1(intron 10)*C haplotype was more common in CMV-retinitis patients than other patients or healthy controls (p<0.01).

Conclusion: The TNFA-308*A/BAT1(intron 10)*C haplotype appears to affect CMV-induced pathology rather than CMV replication.

Keywords: TNF block haplotypes, CMV, HIV, retinitis, ART, viral replication.

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[1]
Hajeer AH, Hutchinson IV. TNF-α gene polymorphism: clinical and biological implications. Microsc Res Tech 2000; 50(3): 216-28.
[http://dx.doi.org/10.1002/1097-0029(20000801)50:3<216:AID-JEMT5>3.0.CO;2-Q] [PMID: 10891887]
[2]
Hornung F, Scala G, Lenardo MJ. TNF-alpha-induced secretion of C-C chemokines modulates C-C chemokine receptor 5 expression on peripheral blood lymphocytes. J Immunol 2000; 164(12): 6180-7.
[http://dx.doi.org/10.4049/jimmunol.164.12.6180] [PMID: 10843668]
[3]
Kumar A, Abbas W, Herbein G. TNF and TNF receptor superfamily members in HIV infection: new cellular targets for therapy? Mediators Inflamm 2013; 2013: 484378.
[http://dx.doi.org/10.1155/2013/484378] [PMID: 24453421]
[4]
Elahi MM, Asotra K, Matata BM, Mastana SS. Tumor necrosis factor alpha -308 gene locus promoter polymorphism: an analysis of association with health and disease. Biochim Biophys Acta 2009; 1792(3): 163-72.
[http://dx.doi.org/10.1016/j.bbadis.2009.01.007] [PMID: 19708125]
[5]
Bayley JP, de Rooij H, van den Elsen PJ, Huizinga TW, Verweij CL. Functional analysis of linker-scan mutants spanning the -376, -308, -244, and -238 polymorphic sites of the TNF-alpha promoter. Cytokine 2001; 14: 316-23.
[6]
Valente FP, Tan CR, Temple SE, et al. The evolution and diversity of TNF block haplotypes in European, Asian and Australian Aboriginal populations. Genes Immun 2009; 10(7): 607-15.
[http://dx.doi.org/10.1038/gene.2009.45] [PMID: 19536152]
[7]
Price P, Bolitho P, Jaye A, et al. A Gambian TNF haplotype matches the European HLA-A1,B8,DR3 and Chinese HLA-A33,B58,DR3 haplotypes. Tissue Antigens 2003; 62(1): 72-5.
[http://dx.doi.org/10.1034/j.1399-0039.2003.00083.x] [PMID: 12859597]
[8]
Chew CS, Cherry CL, Imran D, et al. Tumour necrosis factor haplotypes associated with sensory neuropathy in Asian and Caucasian human immunodeficiency virus patients. Tissue Antigens 2011; 77(2): 126-30.
[http://dx.doi.org/10.1111/j.1399-0039.2010.01570.x] [PMID: 20887379]
[9]
Drew WL. Cytomegalovirus infection in patients with AIDS. Clin Infect Dis 1992; 14(2): 608-15.
[http://dx.doi.org/10.1093/clinids/14.2.608-a] [PMID: 1313313]
[10]
Lestari YD, Sitompul R, Edwar L, Djoerban Z. Ocular diseases among HIV/AIDS patients in Jakarta, Indonesia. Southeast Asian J Trop Med Public Health 2013; 44(1): 62-71.
[PMID: 23682439]
[11]
Price P, Morahan G, Huang D, et al. Polymorphisms in cytokine genes define subpopulations of HIV-1 patients who experienced immune restoration diseases. AIDS 2002; 16(15): 2043-7.
[http://dx.doi.org/10.1097/00002030-200210180-00009] [PMID: 12370503]
[12]
Ariyanto IA, Estiasari R, Waters S, et al. Active and persistent cytomegalovirus infections affect T-cells in young adult HIV patients commencing antiretroviral therapy. Viral Immunol 2018; 31(6): 472-9.
[http://dx.doi.org/10.1089/vim.2018.0014] [PMID: 29688840]
[13]
Edwar L, Karim B, Wijaya IP, et al. Factors Affecting the Health of Retinal Vessels in Human Immunodeficiency Virus Patients Beginning Anti-Retroviral Therapy. AIDS Res Hum Retroviruses 2019; 35(6): 529-35.
[http://dx.doi.org/10.1089/aid.2018.0251] [PMID: 30880399]
[14]
Deghaide NHS, Rodrigues MDLV, Castelli EC, Mendes CT, Figueiredo JFC, Donadi EA. Tumor necrosis factor region polymorphisms are associated with AIDS and with cytomegalovirus retinitis. AIDS 2009; 23: 1641-7.
[http://dx.doi.org/10.1097/QAD.0b013e32832e5591]

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