title: Frequency of coreceptor tropism in PBMC samples from HIV-1 recently infected blood donors by massively parallel sequencing: the REDS II study.
abstract: BACKGROUND
  The interaction of HIV-1 and target cells involves sequential binding of the viral gp120 Env protein to the CD4 receptor and a chemokine co-receptor (either CCR5 or CXCR4). CCR5 antagonists have proved to be an effective salvage therapy in patients with CCR5 using variants (R5) but not with variants capable of using CXCR4 (×4) phenotype. Thus, it is critically important to determine cellular tropism of a country's circulating HIV strains to guide a management decision to improve treatment outcome. In this study, we report the prevalence of R5 and ×4 HIV strains in 45 proviral DNA massively parallel sequencing "MPS" data from recently infected Brazilian blood donors.
  
  
  METHODS
  The MPS data encompassing the tropism-related V3 loop region of the HIV-1 env gene was extracted from our recently published HIV-1 genomes sequenced by a paired-end protocol (Illumina). HIV-1 tropism was inferred using Geno2pheno[coreceptor] algorithm (3.5 % false-positive rate). V3 net charge and 11/25 rules were also used for coreceptor prediction.
  
  
  RESULTS
  Among the 45 samples for which tropism were determined, 39 were exclusively R5 variants, 5 ×4 variants, and one dual-tropic or mixed (D/M) populations of R5 and ×4 viruses, corresponding to 86.7, 11.1 and 2.2 %, respectively. Thus, the proportion of all blood donors that harbor CXCR4-using virus was 13.3 % including individuals with D/M-tropic viruses.
  
  
  CONCLUSIONS
  The presence of CCR5-tropic variants in more than 85 % of our cohort of antiretroviral-naïve blood donors with recent HIV-1 infection indicates a potential benefit of CCR5 antagonists as a therapeutic option in Brazil. Therefore, determination of viral co-receptor tropism is an important diagnostic prerequisite.
authors.affiliation: Department of Pathology, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil. rodrigo_pessoa1@hotmail.com.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Pessôa
authors.affiliation: Department of Infectious Disease/Institute of Tropical Medicine, University of São Paulo, Sao Paulo, Brazil. sabinoec@gmail.com.
authors.forename: Ester C
authors.initials: EC
authors.lastname: Sabino
authors.affiliation: Department of Pathology, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil. sabyem_63@yahoo.com.|Medicina Instituto de Medicina Tropical de São Paulo, LIM 52 - Av. Dr. Enéas Carvalho de Aguiar, 470 - 2° andar - Cerqueira Cesar, 05403-000, Sao Paulo, SP, Brazil. sabyem_63@yahoo.com.
authors.forename: Sabri S
authors.initials: SS
authors.lastname: Sanabani
mesh_terms: D001782:Blood Donors; D001938:Brazil; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015728:Receptors, HIV / Q000378:metabolism*; D056189:Viral Tropism; D053585:Virus Attachment
chemical_list: D015728:Receptors, HIV