Novel HLA class I associations with HIV-1 control in a unique genetically admixed population
Authors: Valenzuela-Ponce Humberto , Alva-Hernández Selma , Garrido-Rodríguez Daniela , Soto-Nava Maribel , García-Téllez Thalía , Escamilla-Gómez Tania , García-Morales Claudia , Quiroz-Morales Verónica Sonia , Tapia-Trejo Daniela , del Arenal-Sánchez Silvia , Prado-Galbarro Francisco-Javier , Hernández-Juan Ramón , Rodríguez-Aguirre Edna , Murakami-Ogasawara Akio , Mejía-Villatoro Carlos , Escobar-Urias Ingrid Y. , Pinzón-Meza Rodolfo , Pascale Juan Miguel , Zaldivar Yamitzel , Porras-Cortés Guillermo , Quant-Durán Carlos , Lorenzana Ivette , Meza Rita I. , Palou Elsa Y. , Manzanero Marvin , Cedillos Rolando A. , Aláez Carmen , Brockman Mark A. , Harrigan P. Richard , Brumme Chanson J. , Brumme Zabrina L. , Ávila-Ríos Santiago , Reyes-Terán Gustavo ,   The Mesoamerican HIV Project Group, Romero-Mora Karla A. , Gómez-Palacio María , Pinto-Cardoso Sandra , Navas Sabrina , García Leticia , Quintana Cristina , Mendoza Yaxelis , Moreira Sumaya , Hernández Bismarck , Murillo Wendy , Carbajal Candy , Parham Leda , Valladares Diana , Pineda Luisa , Flores Dixiana , Motiño Roxana , Umanzor Víctor , Méndez Oneyda , Romero Nadina , Lizama Jonahi , Méndez María L. , Cebrero David de los Santos , Rivera-Benitez César , Sierra-Madero Juan , Alanis-Vega Audelia , González-Hernández Luz A. , Andrade-Villanueva Jaime , Álvarez-Zayas Jaime , Carrillo-Martínez Héctor , Centeno José L. , Barreto Everardo , Campos Tanya , Oaxaca-Navarro Jesús , de la Fuente Ricardo Aya , Carrasco-Ayala César A. , Rivera-Abarca Lesvia M. , Velázquez Gabriela , Papaqui-Limón Elizabeth , Torres-Escobar Indiana , del Carmen-Ricalde María J. , Valenzo-Loaeza David , Barrera-Arellano Carlos A. , Flores-Gaxiola Adrián , Avilez-Gaxiola Carlos A. , Jiménez-Jiménez Adonay , Beltrán-Saldaña Juan , Artega-Martínez Arturo , Domínguez-Ramírez Elizabeth , de la Roca-Chiapas Jorge M. , García-Collins Miriam J. , Basilio-Badillo Hilda , Cruz-Lavadores Dulce M. , González-Álvarez Carlos R. , Arias-Tlaculio Luis E. , Navarro-Álvarez Samuel 
Published: April 2018

Associations between HLA class I alleles and HIV progression in populations exhibiting Amerindian and Caucasian genetic admixture remain understudied. Using univariable and multivariable analyses we evaluated HLA associations with five HIV clinical parameters in 3,213 HIV clade B-infected, ART-naïve individuals from Mexico and Central America (MEX/CAM cohort). A Canadian cohort (HOMER, n = 1622) was used for comparison. As expected, HLA allele frequencies in MEX/CAM and HOMER differed markedly. In MEX/CAM, 13HLA-A, 24HLA-B, and 14HLA-Calleles were significantly associated with at least one clinical parameter. These included previously described protective (e.g.B*27:05,B*57:01/02/03andB*58:01) and risk (e.g.B*35:02) alleles, as well as novel ones (e.g.A*03:01,B*15:39andB*39:02identified as protective, andA*68:03/05,B*15:30,B*35:12/14,B*39:01/06,B*39:05~C*07:02, andB*40:01~C*03:04identified as risk). Interestingly, both protective (e.g.B*39:02) and risk (e.g.B*39:01/05/06) subtypes were identified within the common and genetically diverseHLA-B*39allele group, characteristic to Amerindian populations. While HLA-HIV associations identified in MEX and CAM separately were similar overall (Spearman’s rho = 0.33, p = 0.03), region-specific associations were also noted. The identification of both canonical and novel HLA/HIV associations provides a first step towards improved understanding of HIV immune control among unique and understudied Mestizo populations.