Label-free proteomic analysis of PBMCs reveals gender differences in response to long-term antiretroviral therapy of HIV

• Gender differential analysis in HIV-infected patients on long-term ART was performed by label-free LC–MS/MS.
• A significant, although small influence of gender on HIV treatment was identified at protein levels.
• A potential favorable profile at immunological response to HIV treatment in women was suggested.

The association of gender with the treatment outcome during long-term antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients has been controversial. Here, we performed a comparative proteomic analysis of peripheral blood mononuclear cells (PBMC) by using a label-free shotgun method with nano-LC–MS/MS to investigate the gender differences in responses to long-term ART. This analysis enrolled 30 HIV-infected patients (16 males and 14 females), as well as 20 healthy adults (10 males and 10 females) as control. Quantitative real-time RT-PCR and immunoblotting were used to validate the results of proteomic approach. A total of 53 proteins showing differential expression (± 1.5 fold, p < 0.05) were identified in HIV-infected patients versus healthy adults. Of these proteins, 22 proteins showed identical regulation patterns in both men and women, while 31 proteins were gender-specific (21 men-specific and 10 women-specific proteins). Bioinformatics analysis indicated that long-term ART causes up-regulation of apoptosis, oxidative phosphorylation and mitochondrial dysfunction while down-regulation of oxidative stress and immune system process in men compared to women. These findings point to a concept that gender has a significant influence on the outcomes of ART at protein level and women present a potential favorable immunological pattern and recovery during long-term ART.

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