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J Transl Med. 2014 Dec 5;12:335. doi: 10.1186/s12967-014-0335-6.

Spontaneous control of HIV-1 viremia in a subject with protective HLA-B plus HLA-C alleles and HLA-C associated single nucleotide polymorphisms.

Author information

1
Infectious Disease Unit, Busto Arsizio Public Hospital, P.le Solaro n. 3, Busto Arsizio, 21052, Varese, Italy. marco-alex@libero.it.
2
Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. silvia.ghezzi@hsr.it.
3
Service Lab Fleming Research, Busto Arsizio, Varese, Italy. ibaroli@alice.it.
4
Human Virology Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. silvia.heltai@hsr.it.
5
Human Virology Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. davide.debattista@hsr.it.
6
Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. simone.shimon@gmail.com.
7
Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. mariangela.cavarelli@hsr.it.
8
Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. stefania.dispinseri@hsr.it.
9
Department of Translational Research, Istituto Giannina Gaslini, Genoa, Italy. irenevanni85@yahoo.it.
10
Immunobiology of HIV Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. claudia.pastori@hsr.it.
11
Pathology Unit, Luigi Sacco Hospital, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy. pietro.zerbi@unimi.it.
12
Pathology Unit, Luigi Sacco Hospital, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy. antotosoni@yahoo.it.
13
Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. elisa.vicenzi@hsr.it.
14
Pathology Unit, Luigi Sacco Hospital, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy. manuela.nebuloni@unimi.it.
15
Departments of Microbiology, Medicine and Laboratory Medicine, University of Washington, Seattle, WA, USA. kwong@u.washington.edu.
16
Departments of Microbiology, Medicine and Laboratory Medicine, University of Washington, Seattle, WA, USA. hzhao@u.washington.edu.
17
Departments of Microbiology, Medicine and Laboratory Medicine, University of Washington, Seattle, WA, USA. mchugs2@u.washington.edu.
18
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.
19
School of Medicine, Vita-Salute San Raffaele University, Milan, Italy. guido.poli@hsr.it.
20
Immunobiology of HIV Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. lucia.lopalco@hsr.it.
21
Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. gabriella.scarlatti@hsr.it.
22
Department of Translational Research, Istituto Giannina Gaslini, Genoa, Italy. robertobiassoni@gmail.com.
23
Departments of Microbiology, Medicine and Laboratory Medicine, University of Washington, Seattle, WA, USA. jmullins@uw.edu.
24
Human Virology Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Milan, Italy. mauro.malnati@hsr.it.
25
AIDS Immunopathogenesis Unit, Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Via Olgettina n. 58, Milan, 20132, Italy. massimo.alfano@hsr.it.
26
Present address; Division of Experimental Oncology, Unit of Urology, URI; IRCCS Ospedale San Raffaele, Via Olgettina n. 60, Milan, 20132, Italy. massimo.alfano@hsr.it.

Abstract

INTRODUCTION:

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.

PMID:
25477316
PMCID:
PMC4272524
DOI:
10.1186/s12967-014-0335-6
[Indexed for MEDLINE]
Free PMC Article

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