The impact of integrase inhibitors on steatosis and fibrosis biomarkers in persons with HIV naïve to antiretroviral therapy.

BACKGROUND: Non-alcoholic Fatty Liver Disease (NAFLD) has a high prevalence among persons with HIV infection. Since Integrase Strand Transfer Inhibitors (INSTIs) are used worldwide and have been associated with weight gain, we must determine their effect in the development of NAFLD and Non-alcoholic Steatohepatitis (NASH) in these patients. The aim of this study was to explore the impact of INSTIs on variation of liver steatosis and fibrosis in the ART-naïve person with HIV, using Hepatic Steatosis Index (HSI), Fibrosis-4 Index (FIB-4), BARD score and NAFLD Fibrosis Score (NFS). METHODS: We performed a monocentric, retrospective cohort study in ART-naïve persons with HIV that initiated INSTI based regimens between December 2019 and January 2022. Data was collected at baseline, 6 and 12 months after initiation. Demographic, clinical and laboratory characteristics, hepatic steatosis, and fibrosis scores were compared between baseline and last visit at 12 months. Linear regression models were performed to analyse the associations between analytical data at baseline and hepatic scores variation during the 12 months of treatment. Models were performed unadjusted and adjusted for age and sex. RESULTS: 99 patients were included in our study. 82% were male and median age was 36 years. We observed a significant increase in body mass index (BMI), HDL, platelet count, albumin, and creatinine and a significant decrease in AST levels. HSI showed no statistically significant differences during follow-up (p = 0.114). We observed a significant decrease in FIB-4 (p = 0.007) and NFS (p = 0.002). BARD score showed a significant increase (p = 0.006). The linear regression model demonstrated a significant negative association between baseline HIV RNA and FIB-4 change (ß= -0.08, 95% CI [-0.16 to -0.00], p = 0.045), suggesting that higher HIV RNA loads at baseline were associated with a greater decrease in FIB-4. CONCLUSION: INSTIs seem to have no impact on hepatic steatosis, even though they were associated with a significant increase in BMI. This might be explained by the direct effect of a dolutegravir-containing regimen and/or by the "return-to-health effect" observed with ART initiation. Furthermore, INSTIs were associated with a reduction in risk of liver fibrosis in ART-naïve persons with HIV, possibly due to their effect on viral suppression.

Cutaneous Tuberculosis in Heart Transplant.

Tuberculosis is a disease with a significant global burden in terms of morbidity and mortality. It usually presents as a pulmonary disease but can occasionally have extrapulmonary presentations. Immunosuppressed people are at an increased risk of tuberculosis and more frequently have atypical manifestations of the disease. Cutaneous involvement is estimated to occur in only 2% of extrapulmonary presentations. We report a case of a heart transplant recipient with disseminated tuberculosis who initially presented with cutaneous manifestations in the form of multiple abscesses that were mistaken for a community-acquired bacterial infection. The diagnosis was made after positive nucleic acid amplification testing and cultures for Mycobacterium tuberculosis from the drainage of the abscesses. After initiating antituberculous treatment, the patient had 2 instances of immune reconstitution inflammatory syndrome. A combination of diminished immunosuppression due to discontinuation of mycophenolate mofetil in the setting of acute infection, rifampin drug interactions with cyclosporine, and the beginning of treatment of tuberculosis all contributed to this paradoxical worsening. The patient responded favorably to increased glucocorticoid therapy and showed no signs of treatment failure after 6 months of antituberculous therapy.

The Qrc membrane complex, related to the alternative complex III, is a menaquinone reductase involved in sulfate respiration.

Biological sulfate reduction is a process with high environmental significance due to its major contribution to the carbon and sulfur cycles in anaerobic environments. However, the respiratory chain of sulfate-reducing bacteria is still poorly understood. Here we describe a new respiratory complex that was isolated as a major protein present in the membranes of Desulfovibrio vulgaris Hildenborough. The complex, which was named Qrc, is the first representative of a new family of redox complexes. It has three subunits related to the complex iron-sulfur molybdoenzyme family and a multiheme cytochrome c and binds six hemes c, one [3Fe-4S](+1/0) cluster, and several interacting [4Fe-4S](2+/1+) clusters but no molybdenum. Qrc is related to the alternative complex III, and we show that it has the reverse catalytic activity, acting as a Type I cytochrome c(3):menaquinone oxidoreductase. The qrc genes are found in the genomes of deltaproteobacterial sulfate reducers, which have periplasmic hydrogenases and formate dehydrogenases that lack a membrane subunit for reduction of the quinone pool. In these organisms, Qrc acts as a menaquinone reductase with electrons from periplasmic hydrogen or formate oxidation. Binding of a menaquinone analogue affects the EPR spectrum of the [3Fe-4S](+1/0) cluster, indicating the presence of a quinone-binding site close to the periplasmic subunits. Qrc is the first respiratory complex from sulfate reducers to have its physiological function clearly elucidated.