title: Spontaneous control of HIV-1 viremia in a subject with protective HLA-B plus HLA-C alleles and HLA-C associated single nucleotide polymorphisms.
abstract: BACKGROUND
  Understanding the mechanisms by which some individuals are able to naturally control HIV-1 infection is an important goal of AIDS research. We here describe the case of an HIV-1(+) woman, CASE1, who has spontaneously controlled her viremia for the last 14 of her 20 years of infection.
  
  
  METHODS
  CASE1 has been clinically monitored since 1993. Detailed immunological, virological and histological analyses were performed on samples obtained between 2009 and 2011.
  
  
  RESULTS
  As for other Elite Controllers, CASE1 is characterized by low to undetectable levels of plasma HIV-1 RNA, peripheral blood mononuclear cell (PBMC) associated HIV-1 DNA and reduced in vitro susceptibility of target cells to HIV-1 infection. Furthermore, a slow rate of virus evolution was demonstrated in spite the lack of assumption of any antiretroviral agent. CASE1 failed to transmit HIV-1 to either her sexual male partner or to her child born by vaginal delivery. Normal values and ratios of T and B cells were observed, along with normal histology of the intestinal mucosa. Attempts to isolate HIV-1 from her PBMC and gut-derived cells were unsuccessful, despite expression of normal cell surface levels of CD4, CCRC5 and CXCR4. CASE1 did not produce detectable anti-HIV neutralizing antibodies in her serum or genital mucosal fluid although she displayed potent T cell responses against HIV-1 Gag and Nef. CASE1 also possessed multiple genetic polymorphisms, including HLA alleles (B*14, B*57, C*06 and C*08.02) and HLA-C single nucleotide polymorphisms (SNPs, rs9264942 C/C and rs67384697 del/del), that have been previously individually associated with spontaneous control of plasma viremia, maintenance of high CD4(+) T cell counts and delayed disease progression.
  
  
  CONCLUSIONS
  CASE1 has controlled her HIV-1 viremia below the limit of detection in the absence of antiretroviral therapy for more than 14 years and has not shown any sign of immunologic deterioration or disease progression. Co-expression of multiple protective HLA alleles, HLA-C SNPs and strong T cell responses against HIV-1 proteins are the most likely explanation of this very benign case of spontaneous control of HIV-1 disease progression.
authors.affiliation: Infectious Disease Unit, Busto Arsizio Public Hospital, P.le Solaro n. 3, Busto Arsizio, 21052, Varese, Italy. marco-alex@libero.it.
authors.forename: Marco
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authors.affiliation: Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. silvia.ghezzi@hsr.it.
authors.forename: Silvia
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authors.lastname: Ghezzi
authors.affiliation: Service Lab Fleming Research, Busto Arsizio, Varese, Italy. ibaroli@alice.it.
authors.forename: Paolo
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authors.affiliation: Human Virology Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. silvia.heltai@hsr.it.
authors.forename: Silvia
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authors.lastname: Heltai
authors.affiliation: Human Virology Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. davide.debattista@hsr.it.
authors.forename: Davide
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authors.lastname: De Battista
authors.affiliation: Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. simone.shimon@gmail.com.
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authors.affiliation: Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. mariangela.cavarelli@hsr.it.
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authors.affiliation: Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. stefania.dispinseri@hsr.it.
authors.forename: Stefania
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authors.affiliation: Department of Translational Research, Istituto Giannina Gaslini, Genoa, Italy. irenevanni85@yahoo.it.
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authors.affiliation: Immunobiology of HIV Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. claudia.pastori@hsr.it.
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authors.affiliation: Pathology Unit, Luigi Sacco Hospital, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy. pietro.zerbi@unimi.it.
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authors.affiliation: Pathology Unit, Luigi Sacco Hospital, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy. antotosoni@yahoo.it.
authors.forename: Antonella
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authors.lastname: Tosoni
authors.affiliation: Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. elisa.vicenzi@hsr.it.
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authors.affiliation: Pathology Unit, Luigi Sacco Hospital, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy. manuela.nebuloni@unimi.it.
authors.forename: Manuela
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authors.affiliation: Departments of Microbiology, Medicine and Laboratory Medicine, University of Washington, Seattle, WA, USA. kwong@u.washington.edu.
authors.forename: Kim
authors.initials: K
authors.lastname: Wong
authors.affiliation: Departments of Microbiology, Medicine and Laboratory Medicine, University of Washington, Seattle, WA, USA. hzhao@u.washington.edu.
authors.forename: Hong
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authors.lastname: Zhao
authors.affiliation: Departments of Microbiology, Medicine and Laboratory Medicine, University of Washington, Seattle, WA, USA. mchugs2@u.washington.edu.
authors.forename: Sarah
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authors.lastname: McHugh
authors.affiliation: AIDS Immunopathogenesis Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Via Olgettina n. 58, Milan, 20132, Italy. guido.poli@hsr.it.|School of Medicine, Vita-Salute San Raffaele University, Milan, Italy. guido.poli@hsr.it.
authors.forename: Guido
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authors.lastname: Poli
authors.affiliation: Immunobiology of HIV Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. lucia.lopalco@hsr.it.
authors.forename: Lucia
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authors.lastname: Lopalco
authors.affiliation: Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. gabriella.scarlatti@hsr.it.
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authors.affiliation: Department of Translational Research, Istituto Giannina Gaslini, Genoa, Italy. robertobiassoni@gmail.com.
authors.forename: Roberto
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authors.affiliation: Departments of Microbiology, Medicine and Laboratory Medicine, University of Washington, Seattle, WA, USA. jmullins@uw.edu.
authors.forename: James I
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mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014766:Viremia / Q000235:genetics*
chemical_list: D006680:HLA Antigens