PMID- 35371095
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20220525
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - HLA-B*13, B*35 and B*39 Alleles Are Closely Associated With the Lack of Response 
      to ART in HIV Infection: A Cohort Study in a Population of Northern Brazil.
PG  - 829126
LID - 10.3389/fimmu.2022.829126 [doi]
LID - 829126
AB  - INTRODUCTION: Immune reconstitution failure after HIV treatment is a 
      multifactorial phenomenon that may also be associated with a single polymorphism 
      of human leukocyte antigen (HLA); however, few reports include patients from the 
      Brazilian Amazon. Our objective was to evaluate the association of the 
      immunogenic profile of the "classical" HLA-I and HLA-II loci with treatment 
      nonresponse in a regional cohort monitored over 24 months since HIV diagnosis. 
      MATERIALS AND METHODS: Treatment-free participants from reference centers in the 
      state of Para, Brazil, were enrolled. Infection screening was performed using 
      enzyme immunoassays (Murex AG/AB Combination DiaSorin, UK) and confirmed by 
      immunoblots (Bio-Manguinhos, FIOCRUZ). Plasma viral load was quantified by 
      real-time PCR (ABBOTT, Chicago, Illinois, USA). CD4(+)/CD8(+) T lymphocyte 
      quantification was performed by immunophenotyping and flow cytometry (BD 
      Biosciences, San Jose, CA, USA). Infection was monitored via test and logistics 
      platforms (SISCEL and SICLOM). Therapeutic response failure was inferred based on 
      CD4(+) T lymphocyte quantification after 1 year of therapy. Loci A, B and DRB1 
      were genotyped using PCR-SSO (One Lambda Inc., Canoga Park, CA, USA). Statistical 
      tests were applied using GENEPOP, GraphPad Prism 8.4.3 and BioEstat 5.3. RESULTS: 
      Of the 270 patients monitored, 134 responded to treatment (CD4(+) >/= 500 
      cells/microL), and 136 did not respond to treatment (CD4(+) < 500 cells/microL). The 
      allele frequencies of the loci were similar to heterogeneous populations. The 
      allelic profile of locus B was statistically associated with treatment 
      nonresponse, and the B*13, B*35 and B*39 alleles had the greatest probabilistic 
      influence. The B*13 allele had the highest risk of treatment nonresponse, and 
      carriers of the allele had a detectable viral load and a CD4+ T lymphocyte count 
      less than 400 cells/microL with up to 2 years of therapy. The B*13 allele was 
      associated with a switch in treatment regimens, preferably to efavirenz 
      (EFZ)-based regimens, and among those who switched regimens, half had a history 
      of coinfection with tuberculosis. CONCLUSIONS: The allelic variants of the B 
      locus are more associated with non-response to therapy in people living with HIV 
      (PLHIV) from a heterogeneous population in the Brazilian Amazon.
CI  - Copyright (c) 2022 Pereira, Franca, Costa, Jorge, Mattos, Freire, Ramos, Monteiro, 
      Macedo, Sousa, Santos, Freitas, Costa and Vallinoto.
FAU - Pereira, Leonn Mendes Soares
AU  - Pereira LMS
AD  - Virology Laboratory, Institute of Biological Sciences, Federal University of 
      Para, Belem, Brazil.
FAU - Franca, Eliane Dos Santos
AU  - Franca EDS
AD  - Epstein-Barr Virus Laboratory, Virology Unit, Evandro Chagas Institute, 
      Ananindeua, Brazil.
FAU - Costa, Iran Barros
AU  - Costa IB
AD  - Epstein-Barr Virus Laboratory, Virology Unit, Evandro Chagas Institute, 
      Ananindeua, Brazil.
FAU - Jorge, Erika Vanessa Oliveira
AU  - Jorge EVO
AD  - Department of Immunogenetics, Hemotherapy and Hematology Foundation of the State 
      of Para, Belem, Brazil.
FAU - Mattos, Patricia Jeanne de Souza Mendonca
AU  - Mattos PJSM
AD  - Department of Immunogenetics, Hemotherapy and Hematology Foundation of the State 
      of Para, Belem, Brazil.
FAU - Freire, Amaury Bentes Cunha
AU  - Freire ABC
AD  - Epidemiology and Surveillance Service, Evandro Chagas Institute, Ananindeua, 
      Brazil.
FAU - Ramos, Francisco Luzio de Paula
AU  - Ramos FLP
AD  - Epidemiology and Surveillance Service, Evandro Chagas Institute, Ananindeua, 
      Brazil.
FAU - Monteiro, Talita Antonia Furtado
AU  - Monteiro TAF
AD  - Epstein-Barr Virus Laboratory, Virology Unit, Evandro Chagas Institute, 
      Ananindeua, Brazil.
FAU - Macedo, Olinda
AU  - Macedo O
AD  - Retrovirus Laboratory, Virology Unit, Evandro Chagas Institute, Ananindeua, 
      Brazil.
FAU - Sousa, Rita Catarina Medeiros
AU  - Sousa RCM
AD  - Epstein-Barr Virus Laboratory, Virology Unit, Evandro Chagas Institute, 
      Ananindeua, Brazil.
AD  - School of Medicine, Federal University of Para, Belem, Brazil.
FAU - Dos Santos, Eduardo Jose Melo
AU  - Dos Santos EJM
AD  - Laboratory of Human and Medical Genetics, Institute of Biological Sciences, 
      Federal University of Para, Belem, Brazil.
AD  - Graduate Program in Biology of Infectious and Parasitic Agents, Institute of 
      Biological Sciences, Federal University of Para, Belem, Brazil.
FAU - Freitas, Felipe Bonfim
AU  - Freitas FB
AD  - Retrovirus Laboratory, Virology Unit, Evandro Chagas Institute, Ananindeua, 
      Brazil.
FAU - Costa, Igor Brasil
AU  - Costa IB
AD  - Epstein-Barr Virus Laboratory, Virology Unit, Evandro Chagas Institute, 
      Ananindeua, Brazil.
AD  - Graduate Program in Biology of Infectious and Parasitic Agents, Institute of 
      Biological Sciences, Federal University of Para, Belem, Brazil.
FAU - Vallinoto, Antonio Carlos Rosario
AU  - Vallinoto ACR
AD  - Virology Laboratory, Institute of Biological Sciences, Federal University of 
      Para, Belem, Brazil.
AD  - Graduate Program in Biology of Infectious and Parasitic Agents, Institute of 
      Biological Sciences, Federal University of Para, Belem, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20220316
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-B Antigens)
SB  - IM
MH  - Alleles
MH  - Brazil
MH  - Cohort Studies
MH  - *HIV Infections/drug therapy/genetics
MH  - HLA Antigens/genetics
MH  - HLA-B Antigens/genetics
MH  - Humans
PMC - PMC8966405
OTO - NOTNLM
OT  - B*13
OT  - HIV
OT  - HLA
OT  - immunogenetics
OT  - therapeutic response
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/05 06:00
MHDA- 2022/04/09 06:00
PMCR- 2022/01/01
CRDT- 2022/04/04 05:29
PHST- 2021/12/04 00:00 [received]
PHST- 2022/02/23 00:00 [accepted]
PHST- 2022/04/04 05:29 [entrez]
PHST- 2022/04/05 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.829126 [doi]
PST - epublish
SO  - Front Immunol. 2022 Mar 16;13:829126. doi: 10.3389/fimmu.2022.829126. eCollection 
      2022.