Background: Several lines of evidence suggest that retinoids (retinol-ROL or vitamin A, and its active metabolites,\r\nretinoic acids-RAs) play important pathogenic roles in HIV infection and combination antiretroviral therapy (cART)-\r\nrelated events. We previously reported that antiretrovirals alter RAs synthesis in vitro. We hypothesised that in vivo\r\nserum retinoid concentrations are affected by both cART and HIV infection. This might explain several clinical and\r\nlaboratory abnormalities reported in HIV-infected patients receiving cART.\r\nMethods: The effects of optimal cART and chronic HIV on serum retinoids were firstly assessed longitudinally in 10 HIVinfected\r\nadults (group1 = G1): twice while on optimal cART (first, during long-term and second, during short term cART)\r\nand twice during 2 cART interruptions when HIV viral load (VL) was detectable. Retinoid concentrations during optimal\r\nlong term cART in G1 were compared with cross-sectional results from 12 patients (G2) with suboptimal cART\r\n(detectable VL) and from 28 healthy adults (G3). Serum retinoids were measured by HPLC with ultraviolet detection.\r\nRetinoid concentrations were correlated with VL, CD4 T- cell count and percentages, CD8? fluorescence,\r\ntriglycerides, cholesterol and C-peptide serum levels.\r\nResults: During optimal cART, G1 participants had drastically reduced RAs (0.5 �± 0.3 �µg/dL; P < 0.01) but the\r\nhighest ROL (82 �± 3.0 �µg/dL) concentrations. During cART interruptions in these patients, RAs slightly increased\r\nwhereas ROL levels diminished significantly (P < 0.05). G3 had the highest RAs levels (7.2 �± 1.1 �µg/dL) and serum\r\nROL comparable to values in North Americans. Serum ROL was decreased in G2 (37.7 �± 3.2 �µg/dL; P < 0.01). No\r\ncorrelations were noted between RA and ROL levels or between retinoid concentrations and CD4 T- cell count,\r\nCD8? fluorescence, VL. ROL correlated with triglycerides and cholesterol in G1 (rs = 0.8; P = 0.01).\r\nConclusions: Serum RAs levels are significantly diminished by cART, whereas ROL concentrations significantly\r\ndecreased during uncontrolled HIV infection but augmented with optimal cART. These alterations in retinoid\r\nconcentrations may affect the expression of retinoid-responsive genes involved in metabolic, hormonal and\r\nimmune processes and be responsible for some adverse events observed in HIV-infected persons treated with\r\nantiretrovirals. Further studies should assess concomitant serum and intracellular retinoid levels in different clinical\r\nsituations in larger, homogenous populations.
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