PMID- 28874142
OWN - NLM
STAT- MEDLINE
DCOM- 20171218
LR  - 20201209
IS  - 1471-2334 (Electronic)
IS  - 1471-2334 (Linking)
VI  - 17
IP  - 1
DP  - 2017 Sep 6
TI  - Risk factors for increased immune reconstitution in response to Mycobacterium 
      tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naive 
      patients.
PG  - 606
LID - 10.1186/s12879-017-2700-6 [doi]
LID - 606
AB  - BACKGROUND: Little is known regarding the restoration of the specific immune 
      response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) 
      therapy introduction among TB-HIV patients. In this study, we examined the immune 
      response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to 
      evaluate the response dynamics to different antigens over time. Moreover, we also 
      evaluated the influence of two different doses of efavirenz and the factors 
      associated with immune reconstitution. METHODS: This is a longitudinal study 
      nested in a clinical trial, where cART was initiated during the baseline visit 
      (D0), which occurred 30 +/- 10 days after the introduction of anti-TB therapy. 
      Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. 
      The production of IFN-gamma upon in vitro stimulation with Mtb antigens purified 
      protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at 
      baseline and follow-up visits. RESULTS: Sixty-one patients, all ART-naive, were 
      selected and included in the immune reconstitution analysis; seven (11.5%) 
      developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific 
      immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and 
      increased in the first 60 days after cART initiation. In multivariate analysis, 
      the variables independently associated with increased IFN-gamma production in 
      response to PPD antigen were CD4(+) T cell counts <200 cells/mm(3) at baseline, 
      age, site of tuberculosis, 800 mg efavirenz dose and follow-up CD4(+) T cell 
      counts. Moreover, the factors associated with the production of IFN-gamma in response 
      to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4(+) T cell counts at 
      follow-up visits of >/=200 cells/mm(3). CONCLUSIONS: These findings highlight the 
      differences in immune response according to the specificity of the Mtb antigen, 
      which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-gamma 
      production elicited by PPD and 38 kDa/CFP-10 antigens have a greater magnitude 
      compared to ESAT-6 and are associated with different factors. The low response to 
      ESAT-6, even during immune restoration, suggests that this antigen is not 
      adequate to assess the immune response of immunosuppressed TB-HIV patients.
FAU - da Silva, Tatiana Pereira
AU  - da Silva TP
AD  - Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, Fundacao 
      Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil. tpsilva2000@gmail.com.
FAU - Giacoia-Gripp, Carmem Beatriz Wagner
AU  - Giacoia-Gripp CBW
AD  - Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, Fundacao 
      Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil.
FAU - Schmaltz, Carolina A
AU  - Schmaltz CA
AD  - Clinical Research Laboratory on Mycobacteria - National Institute of Infectious 
      Diseases Evandro Chagas (FIOCRUZ), Rio de Janeiro, Brazil.
FAU - Sant'Anna, Flavia Marinho
AU  - Sant'Anna FM
AD  - Clinical Research Laboratory on Mycobacteria - National Institute of Infectious 
      Diseases Evandro Chagas (FIOCRUZ), Rio de Janeiro, Brazil.
FAU - Saad, Maria Helena
AU  - Saad MH
AD  - Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Fundacao Oswaldo 
      Cruz (FIOCRUZ), Rio de Janeiro, Brazil.
FAU - Matos, Juliana Arruda de
AU  - Matos JA
AD  - Clinical Research Laboratory on Health Surveillance and Immunization - National 
      Institute of Infectious Diseases Evandro Chagas (FIOCRUZ), Rio de Janeiro, 
      Brazil.
FAU - de Lima E Silva, Julio Castro Alves
AU  - de Lima E Silva JCA
AD  - Platform for Clinical Research - National Institute of Infectious Diseases 
      Evandro Chagas (FIOCRUZ), Rio de Janeiro, Brazil.
FAU - Rolla, Valeria Cavalcanti
AU  - Rolla VC
AD  - Clinical Research Laboratory on Mycobacteria - National Institute of Infectious 
      Diseases Evandro Chagas (FIOCRUZ), Rio de Janeiro, Brazil.
FAU - Morgado, Mariza Goncalves
AU  - Morgado MG
AD  - Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, Fundacao 
      Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170906
PL  - England
TA  - BMC Infect Dis
JT  - BMC infectious diseases
JID - 100968551
RN  - 0 (Alkynes)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Benzoxazines)
RN  - 0 (Cyclopropanes)
RN  - 0 (Tuberculin)
RN  - 144058-44-6 (Mycobacterium tuberculosis antigens)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 99YXE507IL (Tenofovir)
RN  - JE6H2O27P8 (efavirenz)
SB  - IM
MH  - AIDS-Related Opportunistic Infections/*immunology
MH  - Adult
MH  - Alkynes
MH  - Anti-HIV Agents/therapeutic use
MH  - Antigens, Bacterial/immunology
MH  - Benzoxazines/administration & dosage/therapeutic use
MH  - Cyclopropanes
MH  - Female
MH  - HIV Infections/*complications/drug therapy/*immunology
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/etiology/immunology
MH  - Interferon-gamma/metabolism
MH  - Longitudinal Studies
MH  - Male
MH  - Mycobacterium tuberculosis/immunology
MH  - Risk Factors
MH  - Tenofovir/therapeutic use
MH  - Tuberculin/immunology
MH  - Tuberculosis/*immunology/virology
PMC - PMC5585929
OTO - NOTNLM
OT  - AIDS
OT  - ELISpot
OT  - IRIS
OT  - Immune response
OT  - Tuberculosis
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All of the patients who participated 
      in the immune response study signed an informed consent form. This protocol was 
      approved by the INI Ethical Board (CAE: 0052.0.009.000-10), affiliated with the 
      Brazilian National Ethics Council (CONEP). CONSENT FOR PUBLICATION: Not 
      applicable. COMPETING INTERESTS: The authors declare that they have no competing 
      interests. The authors alone are responsible for the content and writing of this 
      paper. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to 
      jurisdictional claims in published maps and institutional affiliations.
EDAT- 2017/09/07 06:00
MHDA- 2017/12/19 06:00
PMCR- 2017/09/06
CRDT- 2017/09/07 06:00
PHST- 2017/02/08 00:00 [received]
PHST- 2017/08/22 00:00 [accepted]
PHST- 2017/09/07 06:00 [entrez]
PHST- 2017/09/07 06:00 [pubmed]
PHST- 2017/12/19 06:00 [medline]
PHST- 2017/09/06 00:00 [pmc-release]
AID - 10.1186/s12879-017-2700-6 [pii]
AID - 2700 [pii]
AID - 10.1186/s12879-017-2700-6 [doi]
PST - epublish
SO  - BMC Infect Dis. 2017 Sep 6;17(1):606. doi: 10.1186/s12879-017-2700-6.