Publications by authors named "Ignacio De Los Santos"

Introduction: While the general immune response to Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is well-understood, the long-term effects of Human Immunodeficiency Virus-1/Severe Acute Respiratory Syndrome-Coronavirus-2 (HIV-1/SARS-CoV-2) co-infection on the immune system remain unclear. This study investigates the immune response in people with HIV-1 (PWH) co-infected with SARS-CoV-2 to understand its long-term health consequences.

Methods: A retrospective longitudinal study of PWH with suppressed viral load and SARS-CoV-2 infection was conducted.

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Purpose: Globally, it is estimated that 1.0 million individuals are newly infected by Hepatitis C virus (HCV) every year, and nearly 50 million people live with a chronic infection, according to World Health Organization. To overcome underdiagnosis of HCV infection among hard-to-reach populations, it is essential to develop new rapid and easy-to-use molecular diagnostic systems.

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Background: In patients with hepatitis C virus (HCV) chronic infection and advanced liver disease, the impact of human immunodeficiency virus (HIV) coinfection on the clinical outcome after sustained virological response (SVR) has not been sufficiently clarified. The aim of this study was to compare the mortality after SVR of patients bearing HCV chronic infection and advanced liver fibrosis, with and without HIV-coinfection after a prolonged follow-up.

Methods: This was a prospective multicenter cohort study including individuals with HIV/HCV-coinfection and patients with HCV-monoinfection from Spain, fulfilling: 1) Liver stiffness (LS) ≥9.

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Article Synopsis
  • * Key findings indicated that certain genetic variations in the TYK2 and VIP genes were linked to a reduced severity of the disease, while variations in TLR7 and OAS1 were associated with increased severity.
  • * The research suggests that these genetic markers could help identify individuals at greater risk for severe COVID-19 outcomes.
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  • About 10% of people with HIV experience low-level viremia (LLV) despite antiretroviral therapy, yet the causes and impacts of this condition remain largely unknown, especially within specific viral load ranges and modern treatment methods.
  • The study observed 81 participants, comparing those with LLV to those with suppressed viremia and non-HIV controls, focusing on immune response characteristics and inflammation markers through advanced flow cytometry and immunoassays.
  • Findings indicated that LLV individuals exhibit greater T-cell activation and senescence, along with a decline in certain immune cell types, which could impair their ability to control HIV and harm long-term immune memory.
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Objective: Multiple strategies have been utilised to reduce the incidence of HIV, including PrEP and rapid antiretroviral therapy initiation. The study objectives were to evaluate the efficacy, safety, satisfaction, treatment adherence, and system retention obtained with rapid initiation of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in naïve patients.

Methods: This phase IV, multicenter, open-label, single-arm, 48-week clinical trial enrolled patients between January 2020 and June 2022.

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Article Synopsis
  • - The study investigates how HIV affects the severity of mpox outcomes in a large group of patients from 18 hospitals in Spain, focusing on factors like duration of illness and the presence of complications.
  • - Out of 1,823 patients with PCR-confirmed mpox, around 43% were people living with HIV, with a significant portion having uncontrolled viral loads, leading to higher rates of long or complicated mpox.
  • - The findings suggest that individuals with uncontrolled HIV are at increased risk for severe mpox complications, highlighting the need for timely HIV testing and immediate antiretroviral therapy for those diagnosed.
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Increased recruitment of transitional and non-classical monocytes in the lung during SARS-CoV-2 infection is associated with COVID-19 severity. However, whether specific innate sensors mediate the activation or differentiation of monocytes in response to different SARS-CoV-2 proteins remain poorly characterized. Here, we show that SARS-CoV-2 Spike 1 but not nucleoprotein induce differentiation of monocytes into transitional or non-classical subsets from both peripheral blood and COVID-19 bronchoalveolar lavage samples in a NFκB-dependent manner, but this process does not require inflammasome activation.

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Background: Switching strategy with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) has become a gold standard for people living with HIV (PLWH), achieving high efficacy and safety rates. However, data regarding immune status in long-term real-life cohorts of pretreated patients are needed.

Methods: We performed a multicentre, non-controlled, retrospective study in virologically suppressed PLWH switching to B/F/TAF.

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  • A multicenter study in Madrid analyzed the clinical and epidemiological characteristics of men who have sex with men (MSM) living with HIV who recently acquired hepatitis C (RAHC).
  • Of the 133 enrolled patients, many had prior sexually transmitted diseases and the most common hepatitis C genotype found was G1a; about 11% experienced spontaneous cure, while the treatment success rate was over 90%.
  • The findings suggest high-risk sexual behaviors are prevalent among MSM with RAHC, highlighting the importance of effective treatment strategies for this population.
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  • The study investigates the connection between SARS-CoV-2 viral load (viremia) and genetic variations (SNPs) linked to the severity of COVID-19 in a group of hospitalized patients at University Hospital La Princesa.
  • Out of 340 patients analyzed, only 37.1% had positive viremia, with specific SNPs (like rs2071746 and rs78958998) associated with a higher risk of viremia, while others (like rs11052877 and rs33980500) were linked to a lower risk.
  • The findings suggest that certain genetic variants contribute to differences in SARS-CoV-2 viremia among individuals, highlighting the
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Hepatitis C virus (HCV) coinfection with human immunodeficiency virus (HIV) has a detrimental impact on disease progression. Increasing evidence points to extracellular vesicles (EVs) as important players of the host-viral cross-talk. The microRNAs (miRNAs), as essential components of EVs cargo, are key regulators of normal cellular processes and also promote viral replication, viral pathogenesis, and disease progression.

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Objectives: HIV infection has been associated with lower rates of sustained viral response (SVR) with direct-acting antivirals (DAAs). There are few data on glecaprevir/pibrentasvir (G/P) in HIV/HCV coinfection outside clinical trials.

Methods: The HEPAVIR-DAA cohort, which recruits HIV/HCV-coinfected patients (NCT02057003) and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are two concurrent ongoing multicentre cohorts of patients receiving anti-HCV treatment.

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Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls.

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Background: The high effectiveness and safety of the two-drug (2DRs) strategy using dolutegravir (DTG) plus lamivudine (3TC) have led to international guidelines recommending their use for treatment-naive HIV patients. In virologically suppressed patients, de-escalating from 3DRs to DTG plus either rilpivirine (RPV) or 3TC has shown high rates of virological suppression.

Objectives: This study aimed to compare the real-life data of two multicenter Spanish cohorts of PLWHIV treated with DTG plus 3TC (SPADE-3) or RPV (DORIPEX) as a switch strategy, not only in terms of virological suppression, safety, and durability but also in terms of immune restoration.

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Background: We identified that acute or chronic Hepatitis C (HCV) infection in people living with HIV (PLWHIV) results in different senescence profiles. However, variations in these profiles after HCV elimination, spontaneously or with direct-acting antivirals (DAAs), remain unclear.

Methods: Longitudinal observational study (48 weeks) in 70 PLWHIV: 23 PLWHIV with active HCV-chronic infection (CHC) before and after HCV eradication with DAAs, 12 PLWHIV who spontaneously clarify the HCV (SC), and 35 controls (HIV).

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Dolutegravir (DTG) based dual therapies for treating PLWHIV are a standard of care nowadays. Switching to DTG and lamivudine (3TC) safety and efficacy were proven in TANGO randomized clinical trial. This multicenter retrospective study included 1032 HIV virologically suppressed patients switching to DTG+3TC from 13 Spanish hospitals.

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Introduction: Listeria monocytogenes infection is a severe disease affecting mainly aged people and patients with immune depression. The incidence of listeriosis seems to be increasing. In the present study cases of listeriosis from two hospitals are analyzed with the aims of studying changes in its incidence, clinical forms of presentation and possible factors associated with mortality.

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Background: Although human immunodeficiency virus type 1 (HIV-1) reservoir size is very stable under antiretroviral therapy (ART), individuals exposed to the Hepatitis C virus (HCV) (chronically coinfected and spontaneous clarifiers) show an increase in HIV reservoir size and in spliced viral RNA, which could indicate that the viral protein regulator Tat is being more actively synthesized and, thus, could lead to a higher yield of new HIV. However, it is still unknown whether the effect of HCV elimination with direct-acting antivirals (DAAs) could modify the HIV reservoir and splicing. Methods: This longitudinal study (48 weeks’ follow-up after sustained virological response) involves 22 HIV+-monoinfected individuals, 17 HIV+/HCV- spontaneous clarifiers, and 24 HIV+/HCV+ chronically infected subjects who eliminated HCV with DAAs (all of them aviremic, viral load < 50).

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Switching dual therapy with dolutegravir (DTG) plus rilpivirine (RPV) was assessed in the SWORD-1 and SWORD-2 studies. Real-life data regarding the immunological impact of this approach on CD4+ and CD8+ T lymphocyte counts and the CD4/CD8 ratio are scarce. We evaluated this strategy on the basis of clinical practice data.

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Hepatitis C virus (HCV) infection remains a global health problem, detected only in the early stages by molecular tests. Molecular tests detect HCV RNA, which is very prone to degradation by ribonucleases, reason why blood samples must be transported and stored at - 20 °C, or even - 70 °C for long-term storage. Flinders Technology Associates (FTA) cards are a useful sampling collecting device for dry blood spot (DBS) storage, especially for low and middle-income countries (LMIC).

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Article Synopsis
  • The study explores how CD8 T cell dysfunction affects the immune response to HIV-1 in people on anti-retroviral therapy, emphasizing differences between those on long-term (LT-ARTp) and short-term (ST-ARTp) treatments.
  • Findings indicate that CD8 T cells from individuals on LT-ARTp show improved functionality and memory response, while those on ST-ARTp have more exhaustion markers and less effectiveness in attacking HIV-infected cells.
  • The research suggests that addressing specific metabolic and immune exhaustion factors in ST-ARTp patients could enhance immune responses, paving the way for personalized HIV vaccine strategies.
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By the end of December 2021, coronavirus disease 2019 (COVID-19) produced more than 271 million cases and 5.3 million deaths. Although vaccination is an effective strategy for pandemic control, it is not yet equally available in all countries.

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Article Synopsis
  • - This study examines the long-term effects of switching from a 3-drug regimen (3DR) to a 2-drug regimen (2DR) on inflammation in people with HIV who are starting treatment and have achieved viral suppression.
  • - Researchers found that patients on 3DR experienced a slow decline in inflammatory markers, while those who switched to 2DR showed increases in markers like IL-6 and hs-CRP after three years.
  • - The results suggest that staying on 3DR is linked to better inflammatory health over time compared to 2DR, indicating the need for more research on the implications for non-AIDS-related health issues.
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