Immune restoration affects 10-year survival in people living with HIV/AIDS.

INTRODUCTION: In recent years, a reduction in the life expectancy gap between people living with HIV (PLWH) and the general population has been observed, irrespective of CD4 lymphocyte count, due to widespread access to antiretroviral treatment. The increase in the life expectancy of PLWH has increased awareness of both the ageing process and gender discrepancies in immune restoration and survival. MATERIALS AND METHODS: Longitudinal data were collected for 2240 patients followed up at the Hospital for Infectious Diseases in Warsaw, Poland (n = 1482), and the Department of Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland (n = 758). Immune restoration was measured from the time of starting combination antiretroviral therapy until achieving 500 CD4 lymphocytes/µL, 800 CD4 lymphocytes/µL, and CD4/CD8 lymphocyte ratios of > 0.8 and > 1.0. Full recovery was achieved when the patient was restored to both 800 CD4 lymphocytes/µL and a CD4/CD8 lymphocyte ratio > 1.0. RESULTS: For all endpoints, immune restoration had a protective effect by reducing mortality. Patients who achieved immune restoration had a greater chance of reduced mortality than those who did not achieve immune restoration: for CD4 count > 500 cells/µL, HR = 5.4 (interquartile range: 3.09-9.41), p < 0.001; for CD4 > 800 cells/µL, HR = 5.37 (2.52-11.43), p < 0.001; for CD4/CD8 ratio > 0.8, HR = 3.16 (1.81-5.51), p < 0.001; for CD4/CD8 ratio > 1.0, HR = 2.67 (1.49-5.24), p = 0.001, and for full immune recovery, HR = 3.62 (1.63-8.04), p = 0.002. CONCLUSIONS: Immune restoration remains a powerful factor in improving the survival of PLWH, regardless of the speed of recovery.

Remdesivir Reduces Mortality in Hemato-Oncology Patients with COVID-19.

Introduction: Remdesivir is the first agent with proven clinical efficacy against coronavirus disease 2019 (COVID-19); however, its benefit is associated with early use, and its efficacy has been poorly studied in patients with hemato-oncological diseases, who have an increased risk of a severe course of infection. This study aimed to assess the effects of remdesivir on mortality, mechanical ventilation, and the duration of hospitalization in both the general population and in patients with hemato-oncological diseases. Materials and Methods: Longitudinal data for 4287 patients with confirmed COVID-19 were analyzed, including a subset of 200 individuals with hemato-oncological diseases. In total, 1285 (30.0%) patients received remdesivir, while the remaining patients were treated with other methods. Survival statistics for the 14- and 30-day observation time points were calculated using non-parametric and multivariate Cox models. Results: Mortality for the 14- and 30-day observation time points was notably lower among patients receiving remdesivir (7.2% vs 11.6%, p < 0.001 and 12.7% vs 16.0, p = 0.005, respectively); however, in multivariate models adjusted for age, sex, lung involvement, and lactate dehydrogenase and interleukin-6 levels, the administration of remdesivir did not reduce patient mortality at either the 14-day or 30-day time points. Among patients with haemato-oncological disease, significant survival benefit was observed at 14 and 30 days for patients treated with remdesivir (11.3% vs.16.7% and 24.2% vs 26.1%, respectively; p < 0.001). A favorable effect of remdesivir was also noted for the 14-day time point in multivariate survival analysis (HR:4.03 [95% confidence interval:1.37-11.88]; p = 0.01). Conclusion: Remdesivir significantly reduced the early mortality rate in COVID-19 patients with comorbid hemato-oncological disease, which emphasizes the need to administer this agent to immunosuppressed patients.

Correction: Influence of HLA-B*5701 on 20 year survival rate among patients living with HIV.

[This corrects the article DOI: 10.1371/journal.pone.0255834.].

Factors Influencing Immune Restoration in People Living with HIV/AIDS.

Introduction: Immune restoration is a key clinical aspect that is pursued in the care of human immunodeficiency virus (HIV)-infected patients. Despite effective antiretroviral treatment and undetectable viremia, immune recovery is often incomplete. Materials and methods: Data from 311 Caucasian patients were collected. SNP in CCR2(rs1799864), CX3CR1(rs3732378), HLAC-35(rs9264942), and CCR5(promoter, rs1799988); a 32bp deletion(Δ32) in CCR5; and HLA-B*5701 genotypes were correlated with clinical data and selected endpoints. Kaplan−Meier and Cox proportional hazards models were used to analyze the effects of genetic factors over time. Results: For HLA-B*5701, the effect on the CD4+/CD8+ >0.8 cell ratio was lost within 48 months (HR = 2.04, 95% CI: 1.04−4.03), and the effect on the CD4+ cell count >500 cells/µL was lost within 12 months (HR = 2.12, CI: 1.11−4.04). The effect of CCR2 GG on the CD4+/CD8+ >0.8 cell ratio was lost within 36 months (HR = 1.7, CI: 1.05−2.75). For CCR5 wt/Δ32, the effect on the CD4+/CD8+ >1.0 cell ratio was lost within 24 months (HR = 2.0, CI: 1.08−3.69), and the effect on the CD4+ >800 cells/µL cell count was lost within 18 months (HR = 1.98, CI: 1.14−4.73). Conclusions: Selected genetic polymorphisms, namely CCR2 GG and CCR5 Δ32, and the presence of the HLA-B*5701 allele positively influenced immune restoration in cART-treated patients with HIV/AIDS.

Clinical parameters, selected HLA and chemokine gene variants associated with late presentation into care of people living with HIV/AIDS.

INTRODUCTION: Late presentation into care remains a significant problem in the diagnosis of HIV infection, and may negatively impact the Joint United Nations Program HIV/AIDS elimination targets. Host genetics affects the tempo of HIV disease progression and therefore may influence clinical status at care entry. MATERIALS AND METHODS: Longitudinal data were collected for 863 Caucasian patients followed up at Pomeranian Medical University, Szczecin, Poland. Single nucleotide polymorphisms in CCR2 (rs1799864), CX3CR1 (rs3732378), HLAC-35 (rs9264942), CCR5 promoter (rs1799988) as well as 32 base pair CCR5 mutation and HLA-B*5701 genotypes were correlated with the clinical and immunologic patient status at care entry. Late presentation was defined as baseline CD4 lymphocyte count <350 cells/µL or history of AIDS-defining illness, while advanced HIV disease as baseline CD4 lymphocyte count <200 cells/µL or AIDS. RESULTS: Of the analyzed gene variants, the CCR2 (rs1799864) GG genotype was more frequent among patients presenting for care with a CD4 lymphocyte count <200/µL (82.6% for GG homozygotes vs. 74.5% for allele A carriers, p = 0.01). The presence of the heterozygous wt/Δ32 genotype at the CCR5 gene was associated with a higher frequency of asymptomatic infection (18.9% for wt/Δ32 heterozygotes vs. 12% for wt/wt homozygotes, p = 0.03). As expected, this association was also observed among late presenters compared to patients presenting for care earlier (13.7% vs. 19,7%, respectively, p = 0.04). Finally, HLA-B*5701 was less common among late presenters (5%) compared to patients who entered care early (9.6%, p = 0.01) or patients with advanced HIV disease (8.9% vs. 5.2%, p = 0.02). CONCLUSIONS: Late presentation was associated with the GG homozygous genotype at the CCR2 rs1799864 SNP, while both the HLA-B*5701 variant and the CCR5 wt/Δ32 were associated with more favorable clinical profile at care entry.

Septic Shock Induced by Vibrio Vulnificus in Northern Poland, a Case Report.

INTRODUCTION: Vibrio vulnificus infections are a growing problem worldwide. In recent years, infections with this bacteria have been reported in Central Europe, especially in the German Baltic coast but also in France and Italy. Climate warming causes the sea temperature to increase every year, which translates to an increased risk of infections from the Vibrio group. Most of these are mild and present as wound infections, but some patients develop life-threatening sepsis from either ingestion of infected mollusks or wound lesions that develop into generalized infections. Illness may be associated with necrotizing fasciitis and may require several weeks of therapy, often based on a surgical operation, demarcation of necrosis or limb amputation. A case such as the one described in this manuscript has not been previously described in Poland and demonstrates the need for a multidisciplinary approach to infection with Vibrio vulnificus. CASE PRESENTATION: A 68-year-old patient was pricked with an unknown object in the side of a lower limb during his stay at the Polish seaside. He developed a life-threatening infection in the form of severe sepsis with multiple organ failure. He required broad-spectrum antibiotic therapy, and after obtaining results for Vibrio vulnificus targeted therapy, a surgical operation with skin lesion decompression and fasciotomy was performed. Finally, hyperbaric chamber therapy was given. The patient's general condition improved, and local changes and his vital parameters stabilized. CONCLUSION: Vibrio vulnificus infection may be confused with other causes of skin and subcutaneous tissue infection, although it requires a different approach and different targeted antibiotic therapies. This infection may take the form of a life-threatening disease requiring a multidisciplinary approach.

Influence of HLA-B*5701 on 20 year survival rate among patients living with HIV.

BACKGROUND: The life expectancy of people living with HIV (PLWH) remains shorter than that of the general population, despite significant improvement in the recent years. Mortality in HIV-infected individuals may be associated with a higher viral load at of diagnosis, a lower CD4 count, or clinical variables such as sex or route of transmission. This article investigated the role of the HLA-B*5701 varian on mortality among PLWH. METHODS: Material for the analysis consist of the data of 2,393 patients for whom the HLA-B*57 variant was known. Those patients were followed under the care of the Infectious Diseases Hospital in Warsaw (n = 1555) and the Clinic of Acquired Immunodeficiency of the Pomeranian Medical University in Szczecin (n = 838). Factors such as age, gender, date of HIV diagnosis, route of transmission, date of death, baseline HIV viral load and baseline CD4 counts, were collected, and end-point cross-sectional analyses were marked at 60, 120, 180 and 240 month of observation. RESULTS: HLA-B*5701 allele was found in 133 (5.5%) analyzed cases. Median age was notably higher for HLA-B*5701 positive patients [32.7 (28.3-41.3) vs. 31.6 (26.8-38.3)years p = 0.02]. HLA-B*5701 was associated with lower baseline viral load [4.21 (3.5-4.8) vs. 4.79 (4.2-5.3)log copies/ml p<0.001] and higher CD4count [448 (294.5-662) vs. 352 (176-514) cells/µl p<0.001]. There were no association between HLA-B*5701 and survival for any given end-point. Higher mortality was associated to male gender, intravenous drug users, lower CD4 count at baseline and higher baseline viral load. CONCLUSIONS: In our study, the presence of HLA-B*5701 allel was not associated with mortality rate of HIV infected patients, irrespective of being associated with both higher baseline CD4 + cell count and lower baseline HIV viral load.