The metabolic profile of clinical and immunogenetic factors linked to HIV progression

Abstract

HIV disease progression is generally defined by the time it takes an individual to progress from primary HIV infection to the acquired immunodeficiency syndrome (AIDS). CD4 T-cell count and plasma viral load are validated clinical indicators of disease progression. These parameters are, however, not reliable, varying significantly across HIV-infected persons. The metabolic and biological reasons underlying the variation in these markers of disease progression are not entirely known, but immunogenetic factors are known to contribute significantly. This study compared the plasma metabolic profile (n=96) of untreated HIV positive participants (n=53) presenting clinical and immunogenetic factors previously linked to HIV disease progression. Samples were extracted, derivatised and analysed on the Leco Pegasus 4D system. The samples of participants with high CD4 (500-800 cells/?l) and low CD4 (<250 cells/?l) counts were compared. The samples of participants with median CD4 counts (350-499 cells/?l) with a non-significant versus significant negative correlation with time (termed non-progressors and progressors) and median CD4 counts (350-499 cells/?l) with protective vs non-protective HLA-B alleles, respectively were compared. The samples of participants with low CD4 counts had decreased amino acids, fatty acids and carbohydrates indicating increased protein catabolism and a reduction in the intake and absorption of branched-chain amino acids (BCAAs). Decreased levels of uridine and an increase in microbial metabolites suggests continued viral replication and microbial dysbiosis. The samples of participants with significant negative correlation between CD4 count and time presented with less metabolic variation implying CD4 count over time to not significantly impact on the host metabolism. The samples of participants with non-protective HLA-B alleles reflected a general increase in amino acids, fatty acids, carbohydrates and microbial metabolites. The clinical factor, CD4 was associated with distinct metabolic changes compared to the change in CD4 over time, with trends suggestive of a shift towards the use of these metabolites for energy metabolism. The samples of participants with non-protective HLA-B alleles revealed metabolic changes indicative of immune activation and microbial dysbiosis. Although samples stratified according to clinical and immunogenetic factors displayed distinct metabolite profiles implying varied mechanisms to contribute to differential HIV disease progression, groups with a “poorer” outcome generally showed features with some similarity. While clinical, immune, genetic and other factors have been used to define patient prognosis, a more holistic view into differential disease progression in these patients may benefit from the inclusion of a metabolic component.