Dysregulated Immune Activation in Second-Line HAART HIV plus Patients Is Similar to That of Untreated Patients

Autor(es)

Espindola, Milena S. ^[1] ; Lima, Leonardo J. G. ^[1] ; Soares, Luana S. ^[1] ; Cacemiro, Maira C. ^[1] ; Zambuzi, Fabiana A. ^[1] ; Gomes, Matheus de Souza ^[2] ; Amaral, Laurence R. ^[2] ; Bollela, Valdes R. ^[3] ; Martins-Filho, Olindo A. ^[4] ; Frantz, Fabiani G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14041903 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Uberlandia, FACOM, INGEB, Lab Bioinformat & Anal Mol, Patos De Minas, MG - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-14041903 Ribeirao Preto, SP - Brazil

^[4] Fiocruz MS, Ctr Pesquisas Rene Rachou, Lab Biomarcadores Diagnost & Monitoramento, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 12 DEC 18 2015.
• Citações Web of Science: 7

Resumo

Background Successful highly active antiretroviral therapy (HAART) has changed the outcome of AIDS patients worldwide because the complete suppression of viremia improves health and prolongs life expectancy of HIV-1+ patients. However, little attention has been given to the immunological profile of patients under distinct HAART regimens. This work aimed to investigate the differences in the immunological pattern of HIV-1+ patients under the first- or second-line HAART in Brazil. Methods CD4+ T cell counts, Viral load, and plasma concentration of sCD14, sCD163, MCP-1, RANTES, IP-10, IL-1 beta, IL-6, TNF-alpha, IL-12, IFN-alpha, IFN-gamma, IL-4, IL-5, and IL-10 were assessed for immunological characterization of the following clinical groups: Non-infected individuals (NI; n = 66), HIV-1+ untreated (HIV; n = 46), HIV-1+ treated with first-line HAART (HAART 1; n = 15); and HIV-1+ treated with second-line HAART (HAART 2; n = 15). Results We found that the immunological biosignature pattern of HAART 1 is similar to that of NI individuals, especially in patients presenting slow progression of the disease, while patients under HAART 2 remain in a moderate inflammatory state, which is similar to that of untreated HIV patients pattern. Network correlations revealed that differences in IP-10, TNF-alpha, IL-6, IFN-alpha, and IL-10 interactions were primordial in HIV disease and treatment. Heat map and decision tree analysis identified that IP-10> TNF-alpha > IFN-alpha were the best respective HAART segregation biomarkers. Conclusion HIV patients in different HAART regimens develop distinct immunological biosignature, introducing a novel perspective into disease outcome and potential new therapies that consider HAART patients as a heterogeneous group. (AU)

• Processo FAPESP: 11/24026-3 - Caracterização de células natural killer de pacientes HIV+ e estudo de alterações epigenéticas relacionadas as suas funções e fenótipo
• Beneficiário: Luana Silva Soares
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/12199-0 - Estudo de disfunções na resposta imune inata em pacientes HIV+: correlação com alterações imunológicas e epigenéticas
• Beneficiário: Fabiani Gai Frantz
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 12/02799-3 - Alterações funcionais de macrófagos ativados nos padrões M1 e M2 de pacientes HIV-1+ em resposta a estímulos fúngicos e bacterianos
• Beneficiário: Leonardo Judson Galvão de Lima
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 11/12512-0 - Avaliação de alterações epigenéticas e imunológicas de macrófagos de pacientes infectados pelo vírus da imunodeficiência humana em resposta ao Mycobacterium tuberculosis
• Beneficiário: Milena Sobral Espíndola
• Modalidade de apoio: Bolsas no Brasil - Doutorado