Fatty Acids Composition and HIV Infection: Altered Levels of n-6 Polyunsaturated Fatty Acids Are Associated with Disease Progression

Abstract

Fatty acids (FAs) are important regulators of immune responses and innate defense mechanisms. We hypothesized that disturbed FA metabolism could contribute to the progression of HIV infection. Plasma levels of 45 FAs were analyzed with gas chromatography in healthy controls and HIV-infected patients with regard to Mycobacterium avium complex (MAC) infection. In vitro, we assessed MAC-PPD-induced release of inflammatory cytokines in peripheral and bone marrow mononuclear cells (PBMC and BMMC) according to levels of n-6 polyunsaturated fatty acids (PUFAs). While plasma saturated FAs were higher in HIV infection, PUFAs, and in particular the n-6 PUFA arachidonic acid (AA), were lower in patients with advanced disease. The ratio between AA and precursor dihomo-γ-linolenic acid, reflecting Δ5-desaturase activity, was markedly lower and inversely correlated with plasma HIV RNA levels in these patients. Depletion of AA was observed prior to MAC infection, and MAC-PPD-induced release of TNF and IL-6 in PBMC and BMMC was lower in patients with low plasma AA. Our findings suggest that dysregulated metabolism of n-6 PUFAs may play a role in the progression of HIV infection. While high AA may contribute to chronic inflammation in asymptomatic HIV-infected patients, low AA seems to increase the susceptibility to MAC infection in patients with advanced disease.

Contributing to the management of viral infections through simple immunosensing of the arachidonic acid serum level

“…It is important to note that many studies correlate the serum levels of ARA with the susceptibility and severity of certain individuals to respond to viral infections [ 8 , 11 , 16 – 20 ]. Therefore, the developed bioplatform may be applied, in addition to the management of viral infections, to the implementation of personalized vaccination strategies.…”

“…ARA plays an important role in the regulation of a wide variety of important physiological processes such as preventing cardiovascular diseases, diabetes, and tumors, reducing blood viscosity, and improving intelligence and memory [ 4 ]. On the other hand, numerous investigations correlate the dysregulation in ARA levels with inflammatory processes, heart diseases [ 5 , 6 ], high blood pressure, acute intracerebral hemorrhage [ 7 ], Alzheimer’s disease, lupus, arthritis [ 4 ], HIV [ 8 ], COVID-19 [ 9 – 14 ], and prostate cancer [ 15 ].…”

Circulating immune and plasma biomarkers of time to HIV rebound in HIV controllers treated with vesatolimod

“…Polyunsaturated fatty acids (PUFAs), either free or as components of lipids such as phosphatidylinositol, have inhibitory effects on T-cell signaling and activation ( 57 ), which could contribute to our findings. In a cross-sectional study, plasma fatty acids differed between PLWH and healthy controls, with n-3, n-6, and n-9 PUFAs significantly lower in PLWH and were associated with advanced clinical disease ( 58 ). In particular, disturbed n-6 PUFA metabolism was associated with HIV replication and disease progression, which was not normalized to healthy control levels with ART ( 58 ).…”

“…In a cross-sectional study, plasma fatty acids differed between PLWH and healthy controls, with n-3, n-6, and n-9 PUFAs significantly lower in PLWH and were associated with advanced clinical disease ( 58 ). In particular, disturbed n-6 PUFA metabolism was associated with HIV replication and disease progression, which was not normalized to healthy control levels with ART ( 58 ). It is possible that actions of phosphatidylinositols in our HIV controller group are more similar to those in healthy individuals.…”