Abstract
Treatment of HIV-1-infected patients results in improved clinical and immunological conditions, but severe non-AIDS-related conditions still persist. Novel proteomic platforms have identified inflammatory proteins where abundance is dysregulated in adult treated patients, whereas limited data are available in treated HIV-1 infection of children. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we analyzed specimens from 43 vertically HIV-1-infected children receiving antiretroviral treatment (ART) and matched controls in Ethiopia. The infected children were analyzed as a group and separately, according to age of treatment initiation. Proteins displaying a significantly different abundance between groups were hierarchically clustered and presented in heat maps. Random forest analysis was performed to pin-point proteins discriminating between groups; five proteins (STAMBP, CD5, TFG-α, TRANCE, AXIN1) were the strongest prediction factors for treated HIV-1 infection. TRANCE was previously linked to reduced bone mass levels in HIV-1-infected children. CCL4 chemokine, ligand to HIV-1 co-receptor CCR5, was the most critical protein for successful classification between children who initiated ART at different time points. Our data provide evidence that a dysregulated expression of proteins linked to immunological abnormalities and bone metabolism can be found in HIV-1-infected children with prolonged exposure to ART.
Highlights
In 2015, in order to confine the immunological damage imposed by HIV-1 infection, the WHO recommended antiretroviral therapy (ART) to be initiated in HIV-1-infected children at birth and in adults at diagnosis of HIV-1 infection, possibly already during acute HIV-1 infection
The abundance of 15 proteins (TRANCE, CD5, IL-8, HGF, TGF-α, OSM, 4E-BP1, ST1A1, AXIN1, STAMBP, SIRT2, TNFSF14, CD40, CASP-8 and CD244) was found to be significantly different between the groups once we selected for proteins with p < 0.01 (FDR adjusted); all these 15 proteins were downregulated in the HIV-1 group
The analysis identified eight predictors (TRANCE, STAMBP, AXIN1, CD5, TFG-α, SIRT2, CD40 and IL-8; p < 0.05) that could classify samples into groups with an accuracy of 80.2% (Figure 2A); all eight proteins were found to be downmodulated in the infected group
Summary
In 2015, in order to confine the immunological damage imposed by HIV-1 infection, the WHO recommended antiretroviral therapy (ART) to be initiated in HIV-1-infected children at birth and in adults at diagnosis of HIV-1 infection, possibly already during acute HIV-1 infection. Since the massive ART scale-up availability in low-income countries, the rate of vertical transmission of HIV-1 infection has considerably decreased along with the number of HIV-1-related pediatric deaths. ART administration has a positive impact on a variety of clinical symptoms associated with HIV-1 infection in children [1]. Observations on long-term ART toxicity in adults suggest that ART can be associated with a greater risk of bone conditions such as fractures and osteoporosis [5,6], renal and metabolic disorders [7,8], cardiovascular diseases [9,10], neuropsychological disorders [11] and liver diseases [12,13]. In HIV-1-infected children, very early ART initiation below 12 weeks of age significantly reduces morbidity and mortality [14]; in low-income settings, where difficulties still remain to diagnose HIV-1 infection, the majority of infected infants do not start ART during the first year of life. The global HIV statistics presented from UNAIDS showed that
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