The Continuous Surveillance of InSTI Resistance Could be an Important Public Health Tool in the Fight Against HIV Infection.

AIMS: To evaluate the frequency of the InSTIs mutations in a large cohort of HIV-infected people. BACKGROUND: The Highly Active Anti-Retroviral Therapy (HAART) allows turning HIV infection from a fatal disease to chronic infection, and Integrase Strand Transfer Inhibitors (InSTIs) represent the cornerstone of this treatment. However, the spread of HIV-1 drug resistance mutations represents an emerging threat to the long-term success of HIV treatment programs. OBJECTIVES: To evaluate the trend of the HIV drug resistance to InSTIs in a large cohort of HIVpositive people in order to assess the risk represented by these subjects in the spread of the HIV infection to the community. METHODS: A cross-sectional study was conducted analysing all the InSTIs resistance tests performed in HIV positive subjects during 2017-2019 by the HIV Laboratory of the University Hospital "Gaetano Martino" of Messina, Italy. RESULTS: In 2017-2019, 252 InSTIs resistance tests were performed, with 59 (23.4%), 88 (34.9%), and 105 (41.7%) tests respectively in the three considered years. Overall, 28 (11.1%) samples showed resistance to at least one of the four InSTIs. We observed a significant percentage increase of 95% in the resistance to all four drugs. CONCLUSION: InSTI resistance is not rare. Therefore, continuous surveillance along with incessant health education and a wide offer of the HIV test, can be the most important tools in the fight against HIV infection.

Is Melatonin the Cornucopia of the 21st Century?

Melatonin, an indoleamine hormone produced and secreted at night by pinealocytes and extra-pineal cells, plays an important role in timing circadian rhythms (24-h internal clock) and regulating the sleep/wake cycle in humans. However, in recent years melatonin has gained much attention mainly because of its demonstrated powerful lipophilic antioxidant and free radical scavenging action. Melatonin has been proven to be twice as active as vitamin E, believed to be the most effective lipophilic antioxidant. Melatonin-induced signal transduction through melatonin receptors promotes the expression of antioxidant enzymes as well as inflammation-related genes. Melatonin also exerts an immunomodulatory action through the stimulation of high-affinity receptors expressed in immunocompetent cells. Here, we reviewed the efficacy, safety and side effects of melatonin supplementation in treating oxidative stress- and/or inflammation-related disorders, such as obesity, cardiovascular diseases, immune disorders, infectious diseases, cancer, neurodegenerative diseases, as well as osteoporosis and infertility.

Vitamin D Status Modulates Inflammatory Response in HIV+ Subjects: Evidence for Involvement of Autophagy and TG2 Expression in PBMC.

Conflicting results on the involvement of vitamin D deficiency in inflammatory and immune response in HIV+ subjects are reported. We aimed to characterize the possible influence of vitamin D status on changes in expression of tissue transglutaminase gene (TGM2) and other genes involved in inflammatory response and autophagy in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. HIV+ subjects (n = 57) under antiretroviral therapy (ART) and healthy controls (n = 40) were enrolled. mRNA levels of 1-alpha-hydroxylase (CYP27B1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), TGM2, microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related 5 homolog (ATG5), and Beclin 1 (BECN1) were quantified by real-time PCR. In HIV+ subjects, 25(OH)D3 plasma levels were negatively correlated with time since HIV diagnosis. In PBMC from HIV+ subjects, increases in gene expression of TNF-α and IFN-γ in comparison to controls were observed. The highest increase in TNF-α transcripts was observed in HIV+ subjects with deficient 25(OH)D3 levels. Autophagy-related genes LC3, ATG5, and BECN1 were down-regulated in HIV+ subjects. Moreover, TGM2 transcripts were up-regulated in PBMC from HIV+ subjects with 25(OH)D3 deficiency. Changes observed in PBMC from HIV+ subjects appeared to be dependent on vitamin D status. The present results suggest that vitamin D deficiency is associated with changes in the expression of markers of inflammation and autophagy, resulting in immune cell dysfunction.

Vitamin D status influences transcriptional levels of RANKL and inflammatory biomarkers which are associated with activation of PBMC.

Vitamin D status is involved in the risk of many chronic diseases including cancer, inflammatory and autoimmune disease. The RANK/RANKL/OPG system is also implicated in the orchestration of immune functions. We aimed to investigate the expression of RANKL, OPG and markers of inflammation and immune activation in peripheral blood mononuclear cells (PBMC) from healthy subjects with different 25(OH)D3 plasma levels. The 25(OH)D3 plasma concentrations were assessed by HPLC. The gene expression was evaluated by qRT-PCR. The expression of CYP27B1 was lower in subjects with 25(OH)D3 levels below 50 nmol/L (deficiency) than subjects with both insufficient and sufficient levels of 25(OH)D3. In subjects with deficiency, we observed the up-regulation of RANKL, TNF-α, IFN-γ, ICAM and LFA-1, and a reduction of the anti-inflammatory cytokines IL-13 and IL-4 in comparison to other subjects. Finally, we found a negative correlation between RANKL mRNA levels and 25(OH)D3 and between 25(OH)D3 and ICAM mRNA levels. A positive correlation between ICAM and RANKL was observed. Our results give evidence of the modulatory effects of circulating 25(OH)D3 levels on gene expression of biomarkers of immune activation in PBMC, suggesting the possible use of PBMC as ex-vivo model to characterize molecular mechanisms of immune/inflammatory response in hypovitaminosis conditions.