Sergio Serrano Villar

Sergio Serrano Villar
Hospital Universitario Ramón y Cajal · Departamento de Enfermedades Infecciosas

M.D., Ph.D.

About

135
Publications
32,334
Reads
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3,277
Citations
Citations since 2017
68 Research Items
2640 Citations
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Introduction
My research focus is on the persistence of immune dysfunction in treated HIV disease and in the mechanisms fueling chronic inflammation. I am coordinating an international effort to advance the understanding of the microbiota in HIV disease and the role of therapies aimed at manipulating the microbiome.
Additional affiliations
January 2014 - present
Hospital Universitario Ramón y Cajal
Position
  • MD, PhD
May 2013 - December 2013
University of California, San Francisco
Position
  • PostDoc Position
January 2012 - present
Hospital Universitario Ramón y Cajal
Position
  • PostDoc Position

Publications

Publications (135)
Article
Full-text available
Although the microbiota has largely been associated with the pathogenesis of viral infections, most studies using omics techniques are correlational and hypothesis-generating. The mechanisms affecting the immune responses to viral infections are still being fully understood. Here we focus on the two most important sexually transmitted persistent vi...
Preprint
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Background. People with HIV (PWH) exhibit a markedly increased risk of anal cancer, especially men who have sex with men (MSM), with specific microbiota signatures possibly contributing to greater human papillomavirus (HPV) oncogenic potential. Low specificity of the current screening strategy for detecting high-grade squamous intraepithelial lesio...
Article
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Introduction Variable levels of systemic inflammation are observed in people with HIV (PWH), but the clinical significance of differences among antiretroviral therapy (ART) regimens on associated levels of inflammatory markers is unclear. Based on data from previous epidemiologic studies that defined the predicted change in risk of serious non-AIDS...
Article
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miRNAs dictate relevant virus-host interactions, offering new avenues for interventions to achieve an HIV remission. We aimed to enhance HIV-specific cytotoxic responses—a hallmark of natural HIV control— by miRNA modulation in T cells. We recruited 12 participants six elite controllers and six patients with chronic HIV infection on long-term antir...
Article
Background Tenofovir alafenamide (TAF) has replaced tenofovir disoproxil fumarate (TDF) in many clinical settings. However, concerns remain about potential metabolic complications of TAF. We aimed to evaluate changes in weight, laboratory markers, and metabolic-related clinical events after replacing TDF with TAF. Methods Multicenter prospective c...
Article
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Despite its high prevalence, the mechanisms underlying non-alcoholic fatty liver disease (NAFLD) in people living with HIV (PLWH) are still unclear. In this prospective cohort study, we aim to evaluate differences in plasma fatty acid profiles between HIV-infected and HIV-uninfected participants with NAFLD. We included participants diagnosed with N...
Article
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AimsVaccine response is poor among children living with HIV. The gut microbiota has been identified as a potential target to improve vaccine immunogenicity, but data are scarce in the context of HIV infection.Methods Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected children were randomized to receive a mixture of sy...
Article
Full-text available
While the intestinal microbiome seems a major driver of persistent immune defects in people with HIV (PWH), little is known about its fungal component, the mycobiome. We assessed the inter-kingdom mycobiome-bacteriome interactions, the impact of diet, and the association with the innate and adaptive immunity in PWH on antiretroviral therapy. We inc...
Article
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Background While increased CD8 counts and low CD4/CD8 ratio during treated HIV correlate with immunosenescence, their additional predictive values to identify individuals with HIV at higher risk of clinical events remain controversial. Methods We selected treatment-naive individuals initiating ART from ACTG studies 384, 388, A5095, A5142, A5202, a...
Article
Background: Variations in the ACE2 activity in saliva could explain the striking differences of susceptibility to infection and risk of severe disease. Methods: We analyze the activity of ACE2 in saliva in different population groups across a wide age range and disease status during April to June 2020, and we establish differences between infect...
Article
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While changes in microbiome composition have been associated with HIV, the effect of diet and its potential impact on inflammation remains unclear. Methods: Twenty-seven people living with HIV (PWH) on antiretroviral therapy (ART) were studied. A comprehensive dietary analysis was performed and two types of dietary patterns were determined. We ex...
Article
Objectives: To pinpoint factors associated with low-level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high-efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)-based ART. Methods: We included adults aged > 18 years starting their first ART between 2015...
Article
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Background Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation. Methods Nested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3D...
Article
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BackgroundCOVID‐19 can generate a broad spectrum of severity and symptoms. Many studies analysed the determinants of severity but not among some types of symptoms. More importantly, very few studies analysed patients highly exposed to the virus that nonetheless remain uninfected.Methods We analysed serum levels of ACE2, Angiotensin II and anti-Spik...
Article
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Background The initiation of antiretroviral treatment based on a 2-drug regimen (2DR) with dolutegravir plus lamivudine has demonstrated non-inferior efficacy than dolutegravir-based three-drug regimens (3DR). We aimed to assess whether the treatment initiation with this 2DR has a different impact on the CD4/CD8 ratio recovery than INSTI-based 3DR....
Article
Full-text available
Aims: Children with HIV exhibit chronic inflammation and immune dysfunction despite antiretroviral therapy (ART). Strategies targeting persistent inflammation are needed to improve health in people living with HIV. The gut microbiota likely interacts with the immune system, but the clinical implications of modulating the dysbiosis by nutritional s...
Article
In October of 2020, researchers from around the world met online for the sixth annual International Workshop on Microbiome in HIV Pathogenesis, Prevention, and Treatment. New research was presented on the roles of the microbiome on immune response and HIV transmission and pathogenesis and the potential for alterations in the microbiome to decrease...
Article
Full-text available
In this pilot program of low-dose computed tomography (LDCT) for the screening of lung cancer (LC) in a targeted population of people with HIV (PWH), its prevalence was 3.6%; the number needed to screen in order to detect one case of lung cancer was 28, clearly outweighing the risks associated with lung cancer screening. While data from additional...
Article
Modern ART has now achieved the goal of maintaining HIV RNA suppression with minimum drug-related toxicities. Indeed, in high-income settings, the main health issues in adult people living with HIV (PLWH) today are diseases not directly associated with HIV. These conditions have become the central topic of discussion in HIV clinical forums. While t...
Preprint
Full-text available
Despite of the scientific and human efforts to understand COVID-19, there are questions still unanswered. Variations in the metabolic reaction to SARS-CoV-2 infection could explain the striking differences in the susceptibility to infection and the risk of severe disease. Here, we used untargeted metabolomics to examine novel metabolic pathways rel...
Article
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Introduction Weight gain after starting antiretroviral therapy (ART) is a major problem that can increase morbidity. Our main objective was to evaluate the effects of initial ART on weight change in a large prospective cohort of HIV-positive individuals. Methods This was a prospective cohort study of 13,198 subjects included in the Spanish HIV Res...
Article
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We aim to evaluate the role of single-nucleotide polymorphisms of the angiotensin-converting enzyme 2 in susceptibility to SARS-CoV-2 infection. We included 28 uninfected but highly exposed healthcare workers and 39 hospitalized patients with COVID-19. Thirty-five SNPs were rationally selected. Two variants were associated with increased risk of be...
Article
Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or ex...
Article
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Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on...
Article
Background: While the microbiota has been associated with HPV malignant transformation, it is unclear whether anal bacteria could improve the low specificity of anal cytology for the screening of high grade intraepithelial squamous neoplasia (HSIL). Methodology: We recruited MSM undergoing anal cytology and high-resolution anoscopy. We assessed...
Article
Full-text available
A correct identification of seropositive individuals for the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection is of paramount relevance to assess the degree of protection of a human population to present and future outbreaks of the COVID-19 pandemic. We describe here a sensitive and quantitative flow cytometry method using the...
Article
Reactivation of latent HIV-1 is a necessary step for the purging of the viral reservoir, although it does not seem to be enough. The stimulation of HIV-1 specific cytotoxic T lymphocytes (CTL) may be just as essential for this purpose. In this study, we aimed to show the effect of galectin-9 (Gal-9), known to revert HIV-1 latency, in combination wi...
Article
Objectives To describe and compare the main clinical characteristics and outcome measures in hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) according to geographical area of origin. Methods A retrospective analysis of patients hospitalized with confirmed COVID-19 at a referral centre in Madrid, Spain, during March–May 202...
Article
The number of migrants and travellers has grown in recent decades. This phenomenon is also true of people living with HIV, given their much-improved life expectancy and quality of life. A significant number of travellers with HIV are migrants returning to their home countries to visit friends and relatives (VFRs). This population constitutes a high...
Article
Objectives: Tocilizumab has been proposed as a candidate therapy for patients with severe coronavirus disease 2019 (COVID-19), especially among those with higher systemic inflammation. Here, we investigate the association between tocilizumab use and mortality in a large cohort of hospitalized patients. Methods: Cohort study of patients hospitali...
Article
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Background: The lack of evidence-based recommendations for therapeutic decisions during the early weeks of the COVID-19 pandemic creates a unique scenario of clinical decision making which is worth to analyze. We aim to identify the drivers of therapeutic aggressiveness during the first weeks of the COVID-19 pandemic. Methods: This cross-section...
Preprint
A correct identification of seropositive individuals for the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection is of paramount relevance to assess the degree of protection of a human population to present and future outbreaks of the COVID-19 pandemic. We describe here a sensitive and quantitative flow cytometry method using the...
Article
Background A low CD4/CD8 ratio during antiretroviral therapy (ART) identifies people with heightened immunosenescence and increased risk of mortality. We aimed to assess the effects of integrase strand transfer inhibitor (INSTI)-based, protease inhibitor-based, or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART on long-t...
Article
Human Leukocyte Antigen (HLA) includes a large set of genes with important actions in immune response against viral infection. Numerous studies have revealed the existence of significant associations between certain HLA alleles and the susceptibility and prognosis of different infectious diseases. In this pilot study we analyse the binding affinity...
Article
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Aims: The gut microbiota exerts a critical influence in the immune system. The gut microbiota of human virus immunodeficiency (HIV)-infected children remains barely explored. We aimed to characterize the fecal microbiota in vertically HIV-infected children and to explore the effects of its modulation with a symbiotic nutritional intervention. Met...
Article
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HIV infection impairs mucosal immunity and leads to bacterial translocation, fueling chronic inflammation and disease progression. While this is well established, questions remain about the compositional profile of the translocated bacteria, and to what extent it is influenced by ART. Using 16S rDNA targeted sequencing and shotgun proteomics, we sh...
Preprint
Full-text available
Background While there are no treatments with proven efficacy for patients with severe coronavirus disease 2019 (COVID-19), tocilizumab has been proposed as a candidate therapy, especially among patients with higher systemic inflammation. Methods We conducted a cohort study of patients hospitalized with COVID-19 in Spain. The primary outcome was t...
Article
Full-text available
Background: Cofactors associated with persistently abnormal CD4+:CD8+ T-cell ratio in people with HIV (PWH) on antiretroviral treatment (ART) might change over time as the population of people with HIV ages or as new ART drugs become available. The main objective of our study was to determine the long-term associations of baseline factors, includi...
Article
Background: The CD4/CD8 ratio is an indicator of immunosenescence and a predictor of all-cause mortality in HIV-infected patients. The effects of different ART regimens on CD4/CD8 ratio recovery remain unclear. Methods: Clinical cohort study of ART-treated patients from the CFAR Network of Integrated Clinical Systems (CNICS). We included ART-nai...
Article
Full-text available
There is little information on the effectiveness of the pneumococcal vaccines (PVs), especially for the pneumococcal conjugate vaccines (PCVs), in HIV-infected patients in the modern antiretroviral era. This is a case–control study where cases were people living with HIV (PLWH) with confirmed pneumococcal infection (CPI) and controls were PLWH with...
Article
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Background: We aimed to characterize the impact of ART initiation on GALT at various sites along the gastrointestinal site. Methodology: Peripheral blood and duodenal and rectal biopsies were obtained from 12 HIV and 33 treatment-naïve HIV subjects at baseline and after 9-months ART. Tissue was digested for immunophenotyping. Inflammatory, bacte...
Article
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Background: Alopecia areata is a T-cell-mediated autoimmune disease with an unknown etiopathogenesis. Gut microbiota has been revealed as a key modulator of systemic immunity. Objective: To determine whether patients affected by alopecia universalis present differences in gut bacteria composition compared with healthy controls and investigate po...
Article
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Objectives: The aim of this study was to determine the evolution of renal function in patients receiving one or two inhibitors, according to different baseline factors. Some antiretroviral drugs such as rilpivirine (RPV), dolutegravir (DTG), or cobicistat (COBI), interact with the tubular secretion of creatinine, but there are no data about their...
Article
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HIV infection exerts profound and perhaps irreversible damage to the gut mucosal-associated lymphoid tissues, resulting in long-lasting changes in the signals required for the coordination of commensal colonization and in perturbations at the compositional and functional level of the gut microbiota. These abnormalities in gut microbial communities...
Article
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Human immunodeficiency virus (HIV) infection is characterized by an early depletion of the mucosal associated T helper (CD4+) cells that impair the host immunity and impact the oral and gut microbiomes. Although, the HIV-associated gut microbiota was studied in depth, few works addressed the dysbiosis of oral microbiota in HIV infection and, to our...
Article
Full-text available
This update to the document on antiretroviral therapy (ART) in adults, which has been prepared jointly by GeSIDA and the Spanish National AIDS Plan for the last two decades, supersedes the document published in 2017.¹ The update provides physicians treating HIV-1-infected adults with evidence-based recommendations to guide their therapeutic decisio...
Article
This update to the document on antiretroviral therapy (ART) in adults, which has been prepared jointly by GeSIDA and the Spanish National AIDS Plan for the last two decades, supersedes the document published in 2017.¹ The update provides physicians treating HIV-1-infected adults with evidence-based recommendations to guide their therapeutic decisio...
Article
The analysis of the available databases related to HIV/AIDS confirms a paradigm shift in the patient's life expectancy: now HIV has become a chronic disease, so patients are aging. However, this advance is accompanied by a negative counterpart: due to the increase in the number of years of life gained, there is a prevalence of comorbidities greater...
Article
Full-text available
Background: While nutritional interventions with prebiotics and probiotics seem to exert immunological effects, their clinical implications in HIV-infected subjects initiating ART at advanced HIV disease remain unclear. Methodology: Pilot multicenter randomized, placebo-controlled, double-blind study in which 78 HIV-infected, ART-naive subjects...
Article
HIV infection causes a disruption of gut-associated lymphoid tissue, driving a shift in the composition of gut microbiota. A deeper understanding of the metabolic changes and how they affect the interplay with the host is needed. Here, we assessed functional modifications of HIV-associated microbiota by combining metagenomic and metatranscriptomic...
Article
Full-text available
Objective: In a recent blinded randomized study, we found that in HIV individuals a short supplementation with prebiotics (scGOS/lcFOS/glutamine) ameliorates dysbiosis of total gut bacteria, particularly among viremic untreated patients. Our study goal was to determine the fraction of the microbiota that becomes active during the intervention and...
Article
Full-text available
Maraviroc is a CCR5 antagonist used in the treatment of HIV-1 infection. We and others have suggested that maraviroc could reactivate latent HIV-1. To test the latency-reversing potential of maraviroc and the mechanisms involved, we performed a phase II, single-center, open-label study in which maraviroc was administered for 10 days to 20 HIV-1-inf...
Article
Full-text available
Background Screening of anal cancer in HIV-infected MSM with anal cytology results in high rates of false positive results and elevated burden of high-resolution anoscopies. High-risk HPV up-regulates p16 and Ki67 expression in epithelial cells. We assessed the usefulness of P16/Ki-67 immunostaining cytology for the diagnosis of precancerous anal l...
Article
Full-text available
A low CD4/CD8 ratio during treated HIV infection reflects heightened immune activation and predicts mortality. The effect of different ART regimens on CD4/CD8 ratio recovery remains unclear. We performed a post hoc analysis of the MERIT study, a randomized, double-blind, trial of maraviroc versus efavirenz, in combination with zidovudine-lamivudine...
Article
Full-text available
Purpose of review: It is critical to gain insight into the metabolic pathways by which the microbiota might influence HIV immunopathogenesis to exploit host-microbiota interactions. The aim of this review is to sketch a very broad picture of recent advances in our knowledge of how HIV might affect the microbiota, with a focus on specific gene prod...
Article
Plasma, duodenal, and rectal tissue antiretroviral therapy drug concentrations, HIV-RNA and HIV-DNA copy numbers, and recovery of mucosal immunity were measured before and 9-months after initiation of 3 different antiretroviral therapy regimens in 26 subjects. Plasma and tissue HIV-RNA correlated at baseline and when 9-month declines were compared,...