RESUMO
Background/Objectives: Out of 39.9 million adults living with HIV in 2022, 20 million were women. Despite bearing a significant burden, women remain underrepresented in clinical trials, including those for antiretroviral treatments (ART). This study evaluates the safety and efficacy of the bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) regimen in a real-life cohort of 99 women with HIV (females with HIV, FWH) over 48 and 96 weeks. Methods: A retrospective cohort study utilized data from the Sardinian HIV Network and Sicilian HIV Cohort (SHiNe-SHiC) research group. The study included FWH, who started B/F/TAF as a treatment switch. The primary objectives were achieving and maintaining an HIV RNA level of <50 copies/mL at 48 and 96 weeks. Secondary objectives included treatment safety, durability, and reasons for discontinuation. Data on demographics, viro-immunological markers, lipid profiles, and treatment interruptions were extracted for analysis. Results: Among the 99 FWH, the median age was 51.9 years, and the median duration of HIV was 15.1 years. At baseline, 80.8% had undetectable HIV-RNA, which increased to 93.8% at 96 weeks. There was a statistically significant increase in CD4 cells/mL (48w p < 0.001, 96w p < 0.001) and CD4/CD8 ratio (48w p < 0.009, 96w p < 0.048), and reductions in total cholesterol (48w p < 0.003, 96w p < 0.006) and LDL (48w p < 0.004, 96w p < 0.009) levels at 48 and 96 weeks. Nine treatment interruptions were noted, with one due to adverse events. The regimen was well-tolerated overall. Conclusions: B/F/TAF demonstrated high efficacy and safety in this real-world cohort of FWH, highlighting the critical need for gender-focused research in HIV treatment. Ensuring equitable access to effective treatment options for women is imperative for the global health community's efforts to eliminate HIV.
RESUMO
Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), as a fixed dosed combination, is effective in people living with human immunodeficiency virus (PLWH) previously treated with other therapeutic regimens. The aim of the present retrospective observational real-life study was to analyze virological suppression and immunological, metabolic and safety profile of B/F/TAF. Data were collected from 127 PLHW who switched from any regimen to B/F/TAF. Viral load and virological suppression (viral load <50 copies/ml) were assessed by using real-time PCR methodologies; CD4 and CD8 T cell count as well as CD4/CD8 ratio were determined by cytofluorimetric analyses; other metabolic parameters such as total cholesterol, triglycerides, High- and Low-Density Lipoproteins were assessed by using immunoenzymatic assay. All of the aforementioned parameters were assessed at different timepoints (Baseline, 48 and 96 weeks) for the patients switching to B/F/TAF. Of 127 PLHW [96 (75.6%) male and 31 (24.4%) female, with a mean age of 46.8±10.7 years], 107 PLHW were included in the analysis. The percentage of virologically suppressed PLWH increased from 66.4 to 74.8% at 96 weeks. A statistically significant increase in absolute CD4 (P<0.0001) and CD8 T cell count (P=0.002) was observed. Of importance, there was a significant increase in CD4/CD8 ratio from 0.95 (0.52-1.31) to 1.16 (0.75-1.39) (P=0.003) after 96 weeks. There was a significant decrease in the median values of triglycerides (P<0.0001) and total cholesterol (P<0.0001). Serum creatinine showed a significant increase (P=0.0001). In real life, switching to B/F/T was safe and highly effective both virologically and immunologically. Decrease in cholesterol and triglyceride levels suggested a favorable metabolic profile, which may decrease inflammation, leading to a healthier state and less organ damage.
RESUMO
Introduction: The oncogenic transformation is driven by genetic and epigenetic alterations influencing cancer cell fate. These alterations also result in metabolic reprogramming by modulating the expression of membrane Solute Carrier (SLC) transporters involved in biomolecules trafficking. SLCs act as tumor suppressors or promoters influencing cancer methylome, tumor growth, immune-escape, and chemoresistance. Methods: This in silico study aimed to identify the deregulated SLCs in various tumor types compared to normal tissues by analyzing the TCGA Target GTEx dataset. Furthermore, the relationship between SLCs expression and the most relevant tumor features was tackled along with their genetic regulation mediated by DNA methylation. Results: We identified 62 differentially expressed SLCs, including the downregulated SLC25A27 and SLC17A7, as well as the upregulated SLC27A2 and SLC12A8. Notably, SLC4A4 and SLC7A11 expression was associated with favorable and unfavorable outcome, respectively. Moreover, SLC6A14, SLC34A2, and SLC1A2 were linked to tumor immune responsiveness. Interestingly, SLC24A5 and SLC45A2 positively correlated with anti-MEK and anti-RAF sensitivity. The expression of relevant SLCs was correlated with hypo- and hyper-methylation of promoter and body region, showing an established DNA methylation pattern. Noteworthy, the positive association of cg06690548 (SLC7A11) methylation with cancer outcome suggests the independent predictive role of DNA methylation at a single nucleotide resolution. Discussion: Although our in silico overview revealed a wide heterogeneity depending on different SLCs functions and tumor types, we identified key SLCs and pointed out the role of DNA methylation as regulatory mechanism of their expression. Overall, these findings deserve further studies to identify novel cancer biomarkers and promising therapeutic targets.