PMID- 25406087 OWN - NLM STAT- MEDLINE DCOM- 20160429 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 11 DP - 2014 TI - Host genetic factors associated with symptomatic primary HIV infection and disease progression among Argentinean seroconverters. PG - e113146 LID - 10.1371/journal.pone.0113146 [doi] LID - e113146 AB - BACKGROUND: Variants in HIV-coreceptor C-C chemokine receptor type 5 (CCR5) and Human leukocyte antigen (HLA) genes are the most important host genetic factors associated with HIV infection and disease progression. Our aim was to analyze the association of these genetic factors in the presence of clinical symptoms during Primary HIV Infection (PHI) and disease progression within the first year. METHODS: Seventy subjects diagnosed during PHI were studied (55 symptomatic and 15 asymptomatic). Viral load (VL) and CD4 T-cell count were evaluated. HIV progression was defined by presence of B or C events and/or CD4 T-cell counts <350 cell/mm3. CCR5 haplotypes were characterized by polymerase chain reaction and SDM-PCR-RFLP. HLA-I characterization was performed by Sequencing. RESULTS: Symptoms during PHI were significantly associated with lower frequency of CCR5-CF1 (1.8% vs. 26.7%, p = 0.006). Rapid progression was significantly associated with higher frequency of CCR5-CF2 (16.7% vs. 0%, p = 0.024) and HLA-A*11 (16.7% vs. 1.2%, p = 0.003) and lower frequency of HLA-C*3 (2.8% vs. 17.5%, p = 0.035). Higher baseline VL was significantly associated with presence of HLA-A*11, HLA-A*24, and absence of HLA-A*31 and HLA-B*57. Higher 6-month VL was significantly associated with presence of CCR5-HHE, HLA-A*24, HLA-B*53, and absence of HLA-A*31 and CCR5-CF1. Lower baseline CD4 T-cell count was significantly associated with presence of HLA-A*24/*33, HLA-B*53, CCR5-CF2 and absence of HLA-A*01/*23 and CCR5-HHA. Lower 6-month CD4 T-cell count was associated with presence of HLA-A*24 and HLA-B*53, and absence of HLA-A*01 and HLA-B*07/*39. Moreover, lower 12-month CD4 T-cell count was significantly associated with presence of HLA-A*33, HLA-B*14, HLA-C*08, CCR5-CF2, and absence of HLA-B*07 and HLA-C*07. CONCLUSION: Several host factors were significantly associated with disease progression in PHI subjects. Most results agree with previous studies performed in other groups. However, some genetic factor associations are being described for the first time, highlighting the importance of genetic studies at a local level. FAU - Coloccini, Romina Soledad AU - Coloccini RS AD - Instituto de Investigaciones Biomedicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. FAU - Dilernia, Dario AU - Dilernia D AD - Instituto de Investigaciones Biomedicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. FAU - Ghiglione, Yanina AU - Ghiglione Y AD - Instituto de Investigaciones Biomedicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. FAU - Turk, Gabriela AU - Turk G AD - Instituto de Investigaciones Biomedicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. FAU - Laufer, Natalia AU - Laufer N AD - Instituto de Investigaciones Biomedicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina; Hospital Juan A. Fernandez, Buenos Aires, Argentina. FAU - Rubio, Andrea AU - Rubio A AD - Instituto de Investigaciones Biomedicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. FAU - Socias, Maria Eugenia AU - Socias ME AD - Hospital Juan A. Fernandez, Buenos Aires, Argentina; Fundacion Huesped, Buenos Aires, Argentina. FAU - Figueroa, Maria Ines AU - Figueroa MI AD - Hospital Juan A. Fernandez, Buenos Aires, Argentina; Fundacion Huesped, Buenos Aires, Argentina. FAU - Sued, Omar AU - Sued O AD - Hospital Juan A. Fernandez, Buenos Aires, Argentina; Fundacion Huesped, Buenos Aires, Argentina. FAU - Cahn, Pedro AU - Cahn P AD - Hospital Juan A. Fernandez, Buenos Aires, Argentina; Fundacion Huesped, Buenos Aires, Argentina. FAU - Salomon, Horacio AU - Salomon H AD - Instituto de Investigaciones Biomedicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. FAU - Mangano, Andrea AU - Mangano A AD - Laboratorio de Biologia Celular y Retrovirus, CONICET, Hospital de Pediatria "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina. FAU - Pando, Maria Angeles AU - Pando MA AD - Instituto de Investigaciones Biomedicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141118 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (CCR5 protein, human) RN - 0 (HLA Antigens) RN - 0 (Host-Derived Cellular Factors) RN - 0 (Receptors, CCR5) SB - IM MH - Argentina MH - Blotting, Western MH - CD4 Lymphocyte Count MH - Disease Progression MH - HIV Seropositivity/*genetics MH - HLA Antigens/*genetics MH - Haplotypes/genetics MH - Host-Derived Cellular Factors/*metabolism MH - Humans MH - Polymerase Chain Reaction MH - Polymorphism, Restriction Fragment Length MH - Receptors, CCR5/*genetics MH - Viral Load PMC - PMC4236131 COIS- Competing Interests: One of the authors, Dr. Omar Sued (Fundacion Huesped) is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to PLOS ONE Editorial policies and criteria. EDAT- 2014/11/19 06:00 MHDA- 2016/04/30 06:00 PMCR- 2014/11/18 CRDT- 2014/11/19 06:00 PHST- 2014/07/03 00:00 [received] PHST- 2014/10/20 00:00 [accepted] PHST- 2014/11/19 06:00 [entrez] PHST- 2014/11/19 06:00 [pubmed] PHST- 2016/04/30 06:00 [medline] PHST- 2014/11/18 00:00 [pmc-release] AID - PONE-D-14-29379 [pii] AID - 10.1371/journal.pone.0113146 [doi] PST - epublish SO - PLoS One. 2014 Nov 18;9(11):e113146. doi: 10.1371/journal.pone.0113146. eCollection 2014.