The increased life expectancy of PLHIV (People Living with HIV) and the successful highly combined antiretroviral therapy (cART) poses new clinical challenges regarding aging and its co-morbid condition. It is commonly believed that HIV infection “accelerates” aging. Human immunodeficiency virus type 1 (HIV-1) infection is characterized by inflammation and immune activation that persists despite cART, and that may contribute to the development of co-morbid conditions. In this regard, we aimed to compare current cART regimens in light of premature aging to evaluate differences in their ability to reduce immune activation and inflammation in virologically suppressed patients. We studied a panel of biomarkers (IFN-γ, IL-1β, IL-12p70, IL-2, IL-4, IL-5, IL-6, IL-13, IL-18, GM-CSF, TNF-α, C-reactive protein, D-dimer, soluble CD14), which could provide a non-invasive and affordable approach to monitor HIV-related chronic inflammation. The results of the current study do not provide hard evidence favoring a particular cART regimen, although they show a less favorable regimen profile containing a protease inhibitor. Our data suggest an incomplete reduction of inflammation and immune activation in terms of the effective cART. It is likely that the interest in various biomarkers related to immune activation and inflammation as predictors of clinical outcomes among PLHIV will increase in the future.

Transmitted HIV drug resistance in Bulgaria was first reported in 2015 using data from 1988–2011. We determined the prevalence of surveillance drug resistance mutations (SDRMs) and HIV-1 genetic diversity in Bulgaria during 2012–2020 using polymerase sequences from 1053 of 2010 (52.4%) antiretroviral therapy (ART)-naive individuals. Sequences were analyzed for DRM using the WHO HIV SDRM list implemented in the calculated population resistance tool at Stanford University. Genetic diversity was inferred using automated subtyping tools and phylogenetics. Cluster detection and characterization was performed using MicrobeTrace. The overall rate of SDRMs was 5.7% (60/1053), with 2.2% having resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 1.8% to non-nucleoside reverse transcriptase inhibitors (NNRTIs), 2.1% to protease inhibitors (PIs), and 0.4% with dual-class SDRMs. We found high HIV-1 diversity, with the majority being subtype B (60.4%), followed by F1 (6.9%), CRF02_AG (5.2%), A1 (3.7%), CRF12_BF (0.8%), and other subtypes and recombinant forms (23%). Most (34/60, 56.7%) of the SDRMs were present in transmission clusters of different subtypes composed mostly of male-to-male sexual contact (MMSC), including a 14-member cluster of subtype B sequences from 12 MMSC and two males reporting heterosexual contact; 13 had the L90M PI mutation and one had the T215S NRTI SDRM. We found a low SDRM prevalence amid high HIV-1 diversity among ART-naive patients in Bulgaria during 2012–2020. The majority of SDRMs were found in transmission clusters containing MMSC, indicative of onward spread of SDRM in drug-naive individuals. Our study provides valuable information on the transmission dynamics of HIV drug resistance in the context of high genetic diversity in Bulgaria, for the development of enhanced prevention strategies to end the epidemic.

Background: SARS-CoV-2 can trigger hyperinflammation, leading to severe COVID-19, presenting with pneumonia, acute respiratory distress syndrome (ARDS), and multiple organ failure. Specific biomarkers like leukocytes, CRP, NLR, AST, LDH, D-dimer, ferritin, and IL-6 are associated with disease severity. Anakinra, an IL-1 receptor antagonist, has been proposed to mitigate hyperinflammation, but its clinical efficacy remains uncertain. This study aimed to evaluate the effect of Anakinra on inflammatory biomarkers, oxygenation status, and survival outcomes in hospitalized patients with moderate to severe COVID-19 (according to the National Institute of Health severity scale), compared to standard treatment. Methods: A retrospective analysis included 65 patients (mean age 75.51 ± 9.54 years; 58.5% male, 41.5% female) hospitalized with moderate to severe COVID-19. Patients were divided into two groups: a control group receiving standard treatment (n = 24) and a target group treated with Anakinra (n = 41). Biomarkers and oxygenation status were assessed on Days 0, 3, and 7. Statistical analyses compared the groups for changes in leukocytes, NLR, CRP, AST, LDH, D-dimer, ferritin, and IL-6. Results: Anakinra treatment was associated with significant reductions in leukocytes, NLR, D-dimer, ferritin, IL-6, and CRP by Days 3 and 7. Improvements in oxygenation status were observed, although no survival benefits were noted. The control group showed no significant biomarker changes except for AST and LDH on Day 7. Conclusions: Anakinra demonstrated favorable effects on biomarkers and oxygenation in moderate to severe COVID-19 but did not improve survival. Further studies are needed to validate these findings.

Background and Aim: Measuring serum HBV DNA levels after diagnosing acute hepatitis B is not a routine procedure. Its kinetics, however, could have a significant prognostic importance for the future development of the infection. The aim of our study is to detrmine whether HBV DNA levels could have prognostic value as far as the outcome of the infection is concerned: self-limited disease, fulminant or self-limited infection Material and methods: Our study included a dynamic examination of HBV DNA in 45 patients with acute HBV infection with different outcome-recovery, protrached course and fulminant hepatitis as two forms that differ from the self-limited HBV infection. HBV DNA was measured on the 1 st , 2 nd , 7 th , 30 th , 60 th , 90 th , 180 th day after admission to the hospital using Taq Man HBV DNA Real-time PCR. Results: HBV DNA was found in all patients. In fulminant cases relatively high levels of HBV DNA were found from the very beginning (above 10,000,000 IU/ml) and they were HBeAg(-). In patients who recovered and became HBsAg(-) replication reached maximal levels in the beginning of the symptomatic phase. With the recovery form the symptoms it fell and its disappearance marked the fall of the ALT levels and negativation of the HBsAg. The fall of HBV DNA on the 7 th day from the admission to the hospital and the following disappearance in the range of the 60 th day proved to be predictive for the self-limited course. In patients with protrached hepatitis HBV DNA proved to be with relatively higher levels drom the beginning (p < 0.016, F = 6.196) especially in the HBeAg(+) cases. These levels persisted at the time of 90 th and 180 th day with following chronification. Conclusion: The follow-up of the replication showed, that in the majority of cases the elimination of the virus becomes in the first 2 months. The persistence of the viremia on the 60 th day necessitates its further examination due to the risk of chronification. High risk for protrached course is observed in the anicteric HBeAg(+) cases with relatively high replication (above 100,000,000 IU/ml).

A prospective clinical-epidemiological study was conducted to evaluate the dynamics of biomarkers in hospitalized patients with moderate to severe COVID-19 (according to the National Institute of Health severity scale) treated with Anakinra, compared to those receiving standard treatment. The study included 65 patients with a mean age of 75.51±9.54 years, ranging from 44 to 99 years. Among the study participants, 38 (58.5%) were male and 27 (41.5%) were female. The patients were divided into two groups: control group (standard treatment): 24 patients (36.9%) and target group (Anakinra treatment): 41 patients (63.1%). The results showed a significant relationship between the dynamics of leukocytes, ASAT, LDH, D-dimer, ferritin, and IL-6 and the administration of Anakinra. In the control group, no significant dynamics were observed in leukocyte count, D-dimer, ferritin, or IL-6. A statistically significant decrease in ASAT and LDH values in the control group was noted only on Day 7. In the Anakinra group, significantly (or with borderline statistical significance, p<0.1) lower mean values were observed for leukocytes, NLR, D-dimer, ferritin, and IL-6 on Days 3 and 7 compared to the control group. Additionally, significantly lower CRP values were detected in the Anakinra group on Day 7 compared to the control group.

Lenacapavir, the first approved HIV-1 capsid inhibitor, is now being introduced for both treatment and pre-exposure prophylaxis, yet the capsid-coding region lies outside the pol fragment examined in routine genotypic resistance testing, and baseline data on capsid variability remain scarce, particularly in epidemics dominated by non-B lineages. We applied next-generation sequencing of the HIV-1 gag gene to 103 lenacapavir-naive individuals newly diagnosed in Bulgaria between 2023 and 2025. Nine lineages were identified. Subtype B accounted for 46.6% of the sequences, whereas non-B lineages together predominated (53.4%), led by sub-subtype F1 (13.6%) and CRF01_AE (8.7%); a further 10.7% remained unassigned and grouped predominantly with BF1 recombinant references. The distribution of these lineages differed significantly according to the probable route of transmission (p = 0.007). No major lenacapavir resistance-associated mutation was detected (0 of 103; 95% CI 0.0–3.6). Substitutions at position 107 were the only changes observed at a resistance-associated position: T107S in two individuals and a T107T/S mixture in one (2.9% combined). Notably, the two T107S sequences formed a CRF01_AE pair supported by a bootstrap value of 100, indicating that this accessory polymorphism can persist in closely related viruses. All viruses were genotypically predicted to remain susceptible to lenacapavir. These findings establish a molecular baseline for capsid surveillance in Bulgaria, a South-Eastern European country with a genetically diverse HIV-1 epidemic.