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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Immunological and virological characterization of HIV-1 viremia controllers in the North Region of Brazil

Authors: Samara Tatielle M. Gomes, Érica R. Gomes, Mike B. dos Santos, Sandra S. Lima, Maria Alice F. Queiroz, Luiz Fernando A. Machado, Izaura M. V. Cayres-Vallinoto, Antonio Carlos R. Vallinoto, Marluísa de O. Guimarães Ishak, Ricardo Ishak

Published in: BMC Infectious Diseases | Issue 1/2017

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Abstract

Background

A rare phenotype of clinical non-progressors to AIDS is not well understood and the new protocol for universal treatment, may block the understanding of viral control thus it is crucial to define this controversial group.

Methods

A cohort of 30 persons followed a criteria for viremia control groups 1 (VC1; n = 2) and 2 (VC2; n = 7) and non-viral controllers (NC; n = 21) including number of years of diagnosis, LTCD4+, LTCD8+ counts, plasma viral load and the absence of ART; 241 uninfected control persons were matched to age and sex. Infected persons were regularly examined and submitted to two or three annual laboratory measurements. Polymorphisms and allele frequencies of CCR5Δ32 and SDF1–3’A were detected in the genomic DNA. Plasma levels of cytokines (IL-2, IL-4, IL-5, IL-9, IL-10, IL-13, IL-17 and IFN-y) were measured.

Results

The group investigated is originated from a miscigenetic population and demographic and social characteristics were not significantly relevant. LTCD4+ median values were higher among VC than NC, but significantly lower than uninfected controls. Evolution of LTCD4+ and LTCD8+ counts, showed a slight increase of LTCD4+ among VC, but a significant decrease in the NC. The percentage of annual change in LTCD4+ was also significantly different between the groups. LTCD4+/LTCD8+ ratio was inverted but not significant among the VC, thus the ratio may be a useful biomarker for the VC. A clear signature indicated a change from Th1 to Th2 cytokine profiles from VC to NC, respectively.

Conclusions

The knowledge of viral controllers characteristics in different population groups is important to define a strict universal definition for the sake of learning about the pathogenesis of HIV-1. Data on LTCD4+ seems to be stable and repetitive from published data, but the LTCD8+ response and the significance of LTCD4+/LTCD8+ ratio values are in need to further exploration as biomarkers. The change from Th1 to Th2 cytokine profile may help to design and adjust specific treatment protocols for the group.
Literature
1.
2.
3.
Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J med. 2011;365:493–505.CrossRefPubMedPubMedCentral
4.
Diaz RSD, Vásquez VS. Infecção pelo HIV e terapia antirretroviral em 2012. Brasil: Permanyer Brasil Publicações; 2012.
5.
Sheppard HW, Lang W, Ascher MS, Vittinghoff E, Winkelstein W. The characterization of non-progressors: long-term HIV-1 infection with stable CD4+ T-cell levels. Aids. 1993;7:1159–66.CrossRefPubMed
6.
Cao Y, Qin L, Zhang L, Safrit J, Ho DD. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J med. 1995;332:201–8.CrossRefPubMed
7.
Deeks SG, Walker BD. Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity. 2007;27:406–16.CrossRefPubMed
8.
Lambotte O, Boufassa F, Madec Y, Nguyen A, Goujard C, Meyer L, et al. HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication. Clin Infect Dis. 2005;41:1053–6.CrossRefPubMed
9.
Pereyra F, Addo MM, Kaufmann DE, Liu Y, Miura T, Rathod A, et al. Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy. J Infect Dis. 2008;197:563–71.CrossRefPubMed
10.
Okulicz JF, Marconi VC, Landrum ML, Wegner S, Weintrob A, Ganesan A, et al. Clinical outcomes of elite controllers, viremic controllers, and long-term nonprogressors in the US Department of defense HIV natural history study. J Infect Dis. 2009;200:1714–23.CrossRefPubMed
11.
12.
Walker BD. Elite control of HIV infection: implications for vaccines and treatment. Top HIV med. 2007;15:134–6.PubMed
13.
Sajadi MM, Constantine NT, Mann DL, Charurat M, Dadzan E, Kadlecik P, et al. Epidemiologic characteristics and natural history of HIV-1 natural viral suppressors. J Acquir Immune Defic Syndr. 2009;50:403–8.CrossRefPubMedPubMedCentral
14.
Olson AD, Meyer L, Prins M, Thiebaut R, Gurdasani D, Guiguet M, et al. An evaluation of HIV elite controller definitions within a large seroconverter cohort collaboration. PLoS One. 2014;9:e86719. doi:10.1371/journal.pone.0086719.
15.
Espíndola MS, Soares LS, Galvão-Lima LJ, Zambuzi FA, Cacemiro MC, Brauer VS, et al. HIV infection: focus on the innate immune cells. Immunol res. 2016;64:1118–32.
16.
17.
Platten M, Jung N, Trapp S, Flossdorf P, Meyer-Olson D. Schulze Zur Wiesch J, et al. Cytokine and Chemokine Signature in Elite versus Viremic Controllers Infected with HIV AIDS res hum Retroviruses. 2016;32:579–87.PubMed
18.
19.
Grinsztejn B, Hosseinipour MC, Ribaudo HJ, Swindells S, Eron J, Chen YQ, et al. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial. Lancet Infect Dis. 2014;14:281–90.CrossRefPubMedPubMedCentral
20.
ANRS Temprano 12136 Study Group. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J med. 2015;373:808–22.CrossRef
21.
Insight START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J med. 2015;373:795–807.CrossRef
22.
Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia growth and development study, Multicenter AIDS cohort study, Multicenter hemophilia cohort study, san Francisco City cohort, ALIVE study. Science. 1996;273:1856–62.CrossRefPubMed
23.
Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carrington M, et al. Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE study, hemophilia growth and development study (HGDS), Multicenter AIDS cohort study (MACS), Multicenter hemophilia cohort study (MHCS), san Francisco City cohort (SFCC). Science. 1998;279:389–93.CrossRefPubMed
24.
Ayres M, Ayres MJ, Ayres DL, Santos AS. BioEstat 5.0: aplicações estatísticas nas áreas das ciências biológicas e médicas. 5st ed. Editora Instituto de desenvolvimento sustentável Mamirauá; Brasília IDSM/MCT/CNPq, 2007.
25.
Liu SL, Schacker T, Musey L, Shriner D, McElrath MJ, Corey L, et al. Divergent patterns of progression to AIDS after infection from the same source: HIV type 1 evolution and antiviral responses. J Virol. 1997;71:4284–95.PubMedPubMedCentral
26.
27.
28.
Yang OO, Cumberland WG, Escobar R, Liao D, Chew KW. Demographics and natural history of HIV-1-infected spontaneous controllers of viremia: extremes on a continuum. Aids. 2017;31:1091–8.CrossRefPubMed
29.
Santos SEB, Guerreiro JF. The indigenous contribution to the formation of the population of the Brazilian Amazon region. Rev Bras Genet. 1995;18:311–5.
30.
Okulicz JF, Lambote O. Epidemiology and clinical characteristics of elite controllers. Current Opinion HIV AIDS. 2011;6:163–8.CrossRef
31.
Boritz EA, Darko S, Swaszek L, Wolf G, Wells D, Wu X, et al. Multiple origins of virus persistence during natural control of HIV infection. Cell. 2016;166:1004–15.CrossRefPubMed
32.
Pereyra F, Palmer S, Miura T, Block BL, Wiegand A, Rothchild AC, et al. Persistent low-level viremia in HIV-1 elite controllers and relationship to immunologic parameters. J Infect Dis. 2009;200:984–90.CrossRefPubMedPubMedCentral
33.
Côrtes FH, Passaes CP, Bello G, Teixeira SL, Vorsatz C, Babic D, et al. HIV controllers with different viral load cutoff levels have distinct virologic and immunologic profiles. J Acquir Immune Defic Syndr. 2015;68:377–85.CrossRefPubMedPubMedCentral
34.
Moore DM, Hogg RS, Yip B, Craib K, Wood E, Montaner JS. CD4 percentage is an independent predictor of survival in patients starting antiretroviral therapy with absolute CD4 cell counts between 200 and 350 cells/microL. HIV med. 2006;7:383–8.CrossRefPubMed
35.
Hulgan T, Shepherd BE, Raffanti SP, Fusco JS, Beckerman R, Barkanic G, et al. Absolute count and percentage of CD4+ lymphocytes are independent predictors of disease progression in HIV-infected persons initiating highly active antiretroviral therapy. J Infect Dis. 2007;195:425–31.CrossRefPubMed
36.
Torti C, Prosperi M, Motta D, Digiambenedetto S, Maggiolo F, Paraninfo G, et al. Factors influencing the normalization of CD4+ T-cell count, percentage and CD4+/CD8+ T-cell ratio in HIV-infected patients on long-term suppressive antiretroviral therapy. Clin Microbiol Infect. 2012;18:449–58.CrossRefPubMed
37.
Eholié SP, Badje A, Kouame GM, N'takpe JB, Moh R, Danel C, et al. Antiretroviral treatment regardless of CD4 count: the universal answer to a contextual question. AIDS Res Ther. 2016. doi: 10.​1186/​s12981-016-0111-1.
38.
Mudd PA, Martins MA, Ericsen AJ, Tully DC, Power KA, Bean AT, et al. Vaccine-induced CD8+ T cells control AIDS virus replication. Nature. 2012;491:129–33.CrossRefPubMed
39.
Lécuroux C, Sáez-Cirión A, Girault I, Versmisse P, Boufassa F, Avettand-Fenoël V, et al. Both HLA-B*57 and plasma HIV RNA levels contribute to the HIV-specific CD8+ T cell response in HIV controllers. J Virol. 2014;88:176–87.CrossRefPubMedPubMedCentral
40.
Martins MA, Tully DC, Cruz MA, Power KA, Veloso de Santana MG, Bean DJ, et al. Vaccine-induced simian immunodeficiency virus-specific CD8+ T-cell responses focused on a single nef epitope select for escape variants shortly after infection. J Virol. 2015;89:10802–20.CrossRefPubMedPubMedCentral
41.
Yada Tansiri Y, Rowland-Jones SL, Ananworanich J, Hansasuta P. Clinical outcome of HIV Viraemic controllers and Noncontrollers with normal CD4 counts is exclusively determined by antigen-specific CD8+ T-cell-mediated HIV suppression. PLoS. 2015;10:e0118871. doi:10.​1371/​journal.​pone.​0118871.CrossRef
42.
Grabar S, Selinger-Leneman H, Abgrall S, Pialoux G, Weiss L, Costagliola D. Prevalence and comparative characteristics of long-term nonprogressors and HIV controller patients in the French hospital database on HIV. Aids. 2009;23:1163–9.CrossRefPubMed
43.
Kløverpris HN, Kazer SW, Mjösberg J, Mabuka JM, Wellmann A, Ndhlovu Z, et al. Innate lymphoid cells are depleted irreversibly during acute HIV-1 infection in the absence of viral suppression. Immunity. 2016;44:391–405.CrossRefPubMed
44.
45.
Hsue PY, Hunt PW, Schnell A, Kalapus SC, Hoh R, Ganz P, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. Aids. 2009;23:1059–67.CrossRefPubMedPubMedCentral
46.
Wikby A, Ferguson F, Forsey R, Thompson J, Strindhall J, Löfgren S, et al. An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagenarian humans. J Gerontol a Biol Sci med Sci. 2005;60:556–65.CrossRefPubMed
47.
Hadrup SR, Strindhall J, Køllgaard T, Seremet T, Johansson B, Pawelec G, et al. Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol. 2006;176:2645–53.CrossRefPubMed
48.
Wikby A, Nilsson BO, Forsey R, Thompson J, Strindhall J, Löfgren S, et al. The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning. Mech Ageing dev. 2006;127:695–704.CrossRefPubMed
49.
Bernal Morell E, Serrano Cabeza J, Muñoz Á, Marín I, Masiá M, Gutiérrez F, et al. The CD4/CD8 ratio is inversely associated with carotid intima-media thickness progression in human immunodeficiency virus-infected patients on antiretroviral treatment. AIDS res hum Retrovir. 2016;32:648–53.CrossRefPubMed
50.
Carvalhaes FAPL, Cardoso GL, Vallinoto ACR, Machado LF, Ishak MOG, Ishak R, et al. Frequencies of CCR5∆32, CCR2-64I and SDF1-3’A mutations in human immunodeficiency virus (HIV) seropositive subjects and seronegative individuals from the state of Pará in Brazilian Amazonia. Genet Mol Biol. 2005;28:665–9.
51.
Kaslow RA, Carrington M, Apple R, Park L, Muñoz A, Saah AJ, et al. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat med. 1996;2:405–11.CrossRefPubMed
52.
Magierowska M, Theodorou I, Debré P, Sanson F, Autran B, Rivière Y, et al. Combined genotypes of CCR5, CCR2, SDF1, and HLA genes can predict the long-term nonprogressor status in human immunodeficiency virus-1-infected individuals. Blood. 1999;93:936–41.PubMed
53.
Sáez-Cirión A, Sinet M, Shin SY, Urrutia A, Versmisse P, Lacabaratz C, et al. Heterogeneity in HIV suppression by CD8 T cells from HIV controllers: association with gag-specific CD8 T cell responses. J Immunol. 2009;182:7828–37.CrossRefPubMed
54.
Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, et al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science. 2010;330:1551–7.CrossRefPubMedPubMedCentral
55.
Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995;270:1811–5.CrossRefPubMed
56.
Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996;272:872–7.CrossRefPubMed
57.
Kamat A, Misra V, Cassol E, Ancuta P, Yan Z, Li C, et al. A plasma biomarker signature of immune activation in HIV patients on antiretroviral therapy. PLoS One. 2012: e30881. doi: 10.​1371/​journal.​pone.​0030881.
58.
Noel N, Boufassa F, Lécuroux C, Saez-Cirion A, Bourgeois C, Dunyach-Remy C, et al. Elevated IP10 levels are associated with immune activation and low CD4+ T-cell counts in HIV controller patients. Aids. 2014;28:467–76.CrossRefPubMed
59.
Karlsson AC, Younger SR, Martin JN, Grossman Z, Sinclair E, Hunt PW, et al. Immunologic and virologic evolution during periods of intermittent and persistent low-level viremia. Aids. 2004;18:981–9.CrossRefPubMed
60.
Emery S, Neuhaus JA, Phillips AN, Babiker A, Cohen CJ, Gatell JM, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. 2008;197:1133–44.CrossRefPubMed
61.
Rodger AJ, Fox Z, Lundgren JD, Kuller LH, Boesecke C, Gey D, et al. Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection. J Infect Dis. 2009;200:973–83.CrossRefPubMedPubMedCentral
62.
Clerici M, Shearer GM. The Th1-Th2 hypothesis of HIV infection: new insights. Immunol Today. 1994;15:575–81.CrossRefPubMed
63.
Fenoglio D, Poggi A, Catellani S, Battaglia F, Ferrera A, Setti M, et al. Vdelta1 T lymphocytes producing IFN-gamma and IL-17 are expanded in HIV-1-infected patients and respond to Candida albicans. Blood. 2009;113:6611–8.CrossRefPubMed
64.
de Medeiros RM, Valverde-Villegas JM, Junqueira DM, Gräf T, Lindenau JD, de Mello MG, et al. Rapid and slow progressors show increased IL-6 and IL-10 levels in the pre-AIDS stage of HIV infection. PLoS One. 2016: e0156163. doi: 10.​1371/​journal.​pone.​0156163.
65.
Hayashida T, Gatanaga H, Tanuma J, Oka S. Effects of low HIV type 1 load and antiretroviral treatment on IgG-capture BED-enzyme immunoassay. AIDS res hum Retrovir. 2008;24:495–8.CrossRefPubMed
66.
Bello G, Velasco-de-Castro CA, Bongertz V, Rodrigues CA, Giacoia-Gripp CB, Pilotto JH, et al. Immune activation and antibody responses in non-progressing elite controller individuals infected with HIV-1. J med Virol. 2009;81:1681–90.CrossRefPubMed
67.
Wendel SK, Mullis CE, Eshleman SH, Blankson JN, Moore RD, Keruly JC, et al. Effect of natural and ARV-induced viral suppression and viral breakthrough on anti-HIV antibody proportion and avidity in patients with HIV-1 subtype B infection. PLoS One. 2013: e55525. doi: 10.​1371/​journal.​pone.​0055525.
68.
Williams A, Steffens F, Reinecke C, Meyer D. The Th1/Th2/Th17 cytokine profile of HIV-infected individuals: a multivariate cytokinomics approach. Cytokine. 2013;61:521–6.CrossRefPubMed
69.
Pantaleo G, Menzo S, Vaccarezza M, Graziosi C, Cohen OJ, Demarest JF, et al. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J med. 1995;332:209–16.CrossRefPubMed
70.
Strathdee SA, Veugelers PJ, Page-Shafer KA, McNulty A, Moss AR, Schechter MT, et al. Lack of consistency between five definitions of nonprogression in cohorts of HIV-infected seroconverters. Aids. 1996;10:959–65.CrossRefPubMed
71.
Okulicz JF, Grandits GA, Weintrob AC, Landrum ML, Ganesan A, Crum-Cianflone NF, et al. CD4 T cell count reconstitution in HIV controllers after highly active antiretroviral therapy. Clin Infect Dis. 2010;50:1187–91.CrossRefPubMed
72.
Owen RE, Heitman JW, Hirschkorn DF, Lanteri MC, Biswas HH, Martin JN, et al. HIV+ elite controllers have low HIV-specific T-cell activation yet maintain strong, polyfunctional T-cell responses. Aids. 2010;24:1095–105.CrossRefPubMedPubMedCentral
73.
López M, Soriano V, Peris-Pertusa A, Rallón N, Restrepo C, Benito JM. Elite controllers display higher activation on central memory CD8 T cells than HIV patients successfully on HAART. AIDS res hum Retrovir. 2011;27:157–65.CrossRefPubMed
74.
Sáez-Cirión A, Hamimi C, Bergamaschi A, David A, Versmisse P, Mélard A, et al. Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers. Blood. 2011;118:955–64.CrossRefPubMedPubMedCentral
75.
Eriksson EM, Milush JM, Ho EL, Batista MD, Holditch SJ, Keh CE, et al. Expansion of CD8+ T cells lacking Sema4D/CD100 during HIV-1 infection identifies a subset of T cells with decreased functional capacity. Blood. 2012;119:745–55.CrossRefPubMedPubMedCentral
76.
Pantazis N, Touloumi G, Meyer L, Olson A, Costagliola D, Kelleher AD, et al. The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunological response in later treatment. Aids. 2016;30:879–88.CrossRefPubMedPubMedCentral
Metadata
Title
Immunological and virological characterization of HIV-1 viremia controllers in the North Region of Brazil
Authors
Samara Tatielle M. Gomes
Érica R. Gomes
Mike B. dos Santos
Sandra S. Lima
Maria Alice F. Queiroz
Luiz Fernando A. Machado
Izaura M. V. Cayres-Vallinoto
Antonio Carlos R. Vallinoto
Marluísa de O. Guimarães Ishak
Ricardo Ishak
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-017-2491-9

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