Background: Chronic hepatitis B virus (HBV) infection is common in HIV-positive individuals and increases liver-related mortality. Nucleos(t)ide analogues with activity against both HBV and HIV are widely used in coinfected patients, but its long-term effect on liver disease is unknown. Methods: Clinical outcomes, HBsAg and/or HBeAg clearance, and changes in liver stiffness were longitudinally evaluated retrospectively in all HIV–HBV-coinfected individuals followed at our institution. Results: A total of 92 patients with HIV–HBV coinfection were identified, 19 of them superinfected with hepatitis delta virus. Their median time of follow-up was 35 months. Overall, 94% received lamivudine/emtricitabine and 82% tenofovir. Serum HBV-DNA was undetectable in 89%. Seven patients cleared serum HBsAg (2.6/100 patient-years), in four of them accompanied with anti-HBs seroconversion. Of note, two of them had hepatitis delta. Another 11 out of 42 HBeAg-positive patients cleared HBeAg (9/100 patient-years) and five of them experienced anti-HBe seroconversion. Liver decompensation and death occurred in eight (2.9/100 patient-years) and six (2.2/100 patient-years), respectively. At baseline, liver fibrosis was defined as null-mild (48%), moderate-advanced (28%) or cirrhosis (24%). At last visit, after a median of 40 months in 71 patients, 75% showed no changes, whereas improvement was recognized in 17% and worsening in 8%. Conclusion: Most HIV–HBV-coinfected patients treated with anti-HBV active nucleos(t)ide analogues experience an amelioration of liver fibrosis progression, with low rates of hepatic decompensation and death. Serum HBeAg or HBsAg seroconversion occurs at yearly rates of 9 and 2.6%, respectively, even in patients with delta hepatitis.

Introduction. Incidence of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected persons has dramatically decreased in the highly active

Integration of human immunodeficiency virus type 1 (HIV-1) into the host genome causes global disruption of the chromatin environment. The abundance level of various chromatin-modifying enzymes produces these alterations and affects both the provirus and cellular gene expression. Here, we investigated potential changes in enzyme expression and global DNA methylation in chronically infected individuals with HIV-1 and compared these changes with non-HIV infected individuals. We also evaluated the effect of viral replication and degree of disease progression over these changes. Individuals with HIV-1 had a significant surge in the expression of DNA and histone methyltransferases (DNMT3A and DNMT3B, SETDB1, SUV39H1) compared with non-infected individuals, with the exception of PRMT6, which was downregulated. Some histone deacetylases (HDAC2 and HDAC3) were also upregulated in patients with HIV. Among individuals with HIV-1 with various degrees of progression and HIV control, the group of treated patients with undetectable viremia showed greater differences with the other two groups (untreated HIV-1 controllers and non-controllers). These latter two groups exhibited a similar behavior between them. Of interest, the overexpression of genes that associate with viral protein Tat (such as SETDB1 along with DNMT3A and HDAC1, and SIRT-1) was more prevalent in treated patients. We also observed elevated levels of global DNA methylation in individuals with HIV-1 in an inverse correlation with the CD4/CD8 ratio. The current study shows an increase in chromatin-modifying enzymes and remodelers and in global DNA methylation in patients with chronic HIV-1 infection, modulated by various levels of viral control and progression.

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) hijack the host exosomal machinery as an additional mechanism of infection and evasion of the immune system, modifying the small RNA (smRNA) cargo during infection. We characterized the surface epitopes of extracellular vesicles (EVs) from plasma HIV/HCV-coinfected patients and their smRNA cargo profile, by comparing different isolation procedures. Six EVs isolation procedures were compared: ultracentrifugation, and five different polyethylene glycol-based methods (commercial, combined with a column purification step and two custom); and two RNA commercial kits (phenol and non-phenol based) were used. High-throughput sequencing of smRNAs was performed. Exosomal surface epitopes were analyzed by the MACSPlex Exosome Kit. Four miRNAs displayed differences among protocols (hsa-miR-205-5p and hsa-let-7a/b/f-5p). The selection of RNA isolation kit impacted on the detection of miRNAs and other smRNAs, where the phenol-based RNA isolation kit performed acceptably. EVs surface was enriched with HLA-DR/DP/DQ, CD81, and CD8. There were three liver-specific miRNAs overexpressed (let-7a-5p, miR-21-5p and hsa-miR-122-5p), thus, EVs cargo might reflect liver disease evolution. Other smRNAs such as piwi-interacting RNAs were also detected for the first time. Custom polyethylene glycol precipitation-based methods combined with an RNA phenol-based kit yielded the higher number of smRNAs for EVs isolated from plasma HIV/HCV patients.

Dual chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are recognized in 3%–5% of human immunodeficiency virus (HIV)—infected individuals. More severe liver disease is seen in these patients. Viral interference may account for the fact that replication of one virus generally redominates over replication of the other. The impact that treatment of HBV or HCV infection has on this reciprocal inhibition is not well established. No evidence of reactivation of either HBV or HCV was seen when complete suppression of the other predominant virus was achieved with specific therapy in 21 subjects with HIV infection and dual HBV/HCV infections. This information has important pathogenic implications and may influence therapeutic decisions.