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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: PLoS One; v. 10, n. 12 DEC 18 2015.
• Web of Science Citations: 7

Abstract

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)

• FAPESP's process: 11/24026-3 - Characterization of natural killer cells from HIV+ patients and the study of epigenetic changes related to their function and phenotype
• Grantee: Luana Silva Soares
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/12199-0 - Elucidation of innate immune response dysfunction of HIV patients: the underlying mechanisms amongst immunological and epigenetic modifications
• Grantee: Fabiani Gai Frantz
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 12/02799-3 - Functional changes of macrophages activated in M1 and M2 patterns derived from HIV-1+ patients in response to fungal and bacterial stimuli
• Grantee: Leonardo Judson Galvão de Lima
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 11/12512-0 - Evaluation of epigenetic and immune alterations of macrophages from patients infected with human immunodeficiency virus in response to Mycobacterium tuberculosis
• Grantee: Milena Sobral Espíndola
• Support Opportunities: Scholarships in Brazil - Doctorate