Abstract
We assessed the effect of untreated HIV infection as well as different antiretroviral therapy (ART) on the metabolome/lipidome. Widely-targeted plasma metabolomic and lipidomic profiling was performed on HIV-seronegative individuals and persons living with HIV (PLHIV) before and after initiating ART [tenofovir/emtricitabine plus atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r) or raltegravir (RAL)]. Orthogonal partial least squares discriminant analysis was used to assess metabolites/lipid subspecies that discriminated between groups. Graphical lasso estimated group-specific metabolite/lipid subspecies networks associated with the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR). Correlations between inflammatory markers and metabolites/lipid subspecies were visualized using heat maps. Of 435 participants, 218 were PLHIV. Compared to HIV-seronegative individuals, ART-naïve PLHIV exhibited higher levels of saturated triaclyglycerols (TAGs) and 3-hydroxy-kynurenine, lower levels of unsaturated TAGs and N-acetyl-tryptophan, and a sparser and less heterogeneous network of metabolites/lipid subspecies associated with HOMA-IR. PLHIV on RAL vs. ATV/r or DRV/r had lower saturated and unsaturated TAGs. Positive correlations were found between medium-long chain acylcarnitines (C14-C6 ACs), palmitate and HOMA-IR for RAL but not ATV/r or DRV/r. Stronger correlations were seen for TAGs with IL-6 and hsCRP after RAL vs ATV/r or DRV/r initiation; these correlations were absent in ART-naïve PLHIV. Alterations in the metabolome/lipidome suggest increased lipogenesis for ART-naïve PLHIV vs. HIV-seronegative individuals, increased TAG turnover for RAL vs. ATV/r or DRV/r, and increased inflammation associated with this altered metabolome/lipidome after initiating ART. Future studies are needed to understand cardiometabolic consequences of lipogenesis and inflammation in PLHIV. We assessed the effect of untreated HIV infection as well as different antiretroviral therapy (ART) on the metabolome/lipidome. Widely-targeted plasma metabolomic and lipidomic profiling was performed on HIV-seronegative individuals and persons living with HIV (PLHIV) before and after initiating ART [tenofovir/emtricitabine plus atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r) or raltegravir (RAL)]. Orthogonal partial least squares discriminant analysis was used to assess metabolites/lipid subspecies that discriminated between groups. Graphical lasso estimated group-specific metabolite/lipid subspecies networks associated with the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR). Correlations between inflammatory markers and metabolites/lipid subspecies were visualized using heat maps. Of 435 participants, 218 were PLHIV. Compared to HIV-seronegative individuals, ART-naïve PLHIV exhibited higher levels of saturated triaclyglycerols (TAGs) and 3-hydroxy-kynurenine, lower levels of unsaturated TAGs and N-acetyl-tryptophan, and a sparser and less heterogeneous network of metabolites/lipid subspecies associated with HOMA-IR. PLHIV on RAL vs. ATV/r or DRV/r had lower saturated and unsaturated TAGs. Positive correlations were found between medium-long chain acylcarnitines (C14-C6 ACs), palmitate and HOMA-IR for RAL but not ATV/r or DRV/r. Stronger correlations were seen for TAGs with IL-6 and hsCRP after RAL vs ATV/r or DRV/r initiation; these correlations were absent in ART-naïve PLHIV. Alterations in the metabolome/lipidome suggest increased lipogenesis for ART-naïve PLHIV vs. HIV-seronegative individuals, increased TAG turnover for RAL vs. ATV/r or DRV/r, and increased inflammation associated with this altered metabolome/lipidome after initiating ART. Future studies are needed to understand cardiometabolic consequences of lipogenesis and inflammation in PLHIV.
