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

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-1β, IL-6, TNF-α, IL-12, IFN-α, IFN-γ, 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-α, IL-6, IFN-α, and IL-10 interactions were primordial in HIV disease and treatment. Heat map and decision tree analysis identified that IP-10>TNF-α>IFN-α 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.

Below:  Systemic interaction of immunological biomarkers is modified in the course of HIV disease and according to treatment regimen. The network analysis shows significant correlations (p<0.05) among all the variables, which were measured after calculation of Spearman correlation for each pair of biomarkers, and are represented by lines for NI, HIV, HAART 1, and HAART 2 groups. The strength of the correlation was given by “r” value and is illustrated as negative (r < 0), weak (r ≤ 0.35); moderate (0.36 ≤ r ≤ 0.67); or strong (r ≥ 0.68). Arrows indicate the main biomarkers modified during HIV infection.

Full article at:  http://goo.gl/AUudgr

By:   

Milena S. Espíndola, Leonardo J. G. Lima, Luana S. Soares, Maira C. Cacemiro, Fabiana A. Zambuzi, Fabiani G. Frantz

Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil

Matheus de Souza Gomes, Laurence R. Amaral

Laboratorio de Bioinformatica e Analises Moleculares – INGEB / FACOM, Universidade Federal de Uberlandia, Patos de Minas, MG, Brazil

Valdes R. Bollela

Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil

Olindo A. Martins-Filho

Laboratorio de Biomarcadores para Diagnostico e Monitoramento, Centro de Pesquisas Rene Rachou, FIOCRUZ, Belo Horizonte, MG, Brazil

 

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