Immune checkpoint inhibitors as potential therapy for reverting T-cell exhaustion and reverting HIV latency in people living with HIV.

The immune system of people living with HIV (PLWH) is persistently exposed to antigens leading to systemic inflammation despite combination antiretroviral treatment (cART). This inflammatory milieu promotes T-cell activation and exhaustion. Furthermore, it produces diminished effector functions including loss of cytokine production, cytotoxicity, and proliferation, leading to disease progression. Exhausted T cells show overexpression of immune checkpoint molecules (ICs) on the cell surface, including programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), and lymphocyte activation gene-3 (LAG-3). The ICs also play a crucial role in T-cell exhaustion by reducing the immune response to cancer antigens. Immunotherapy based on immune checkpoint inhibitors (ICIs) has changed the management of a diversity of cancers. Additionally, the interest in exploring this approach in the setting of HIV infection has increased, including AIDS-defining cancers and non-AIDS-defining cancers in PLWH. To date, research on this topic suggests that ICI-based therapies in PLWH could be a safe and effective approach. In this review, we provide an overview of the current literature on the potential role of ICI-based immunotherapy not only in cancer remission in PLWH but also as a therapeutic intervention to restore immune response against HIV, revert HIV latency, and attain a functional cure for HIV infection.

IL7RA rs10491434 polymorphism is related to spontaneous HIV infection control in naïve HIV-infected patients: A retrospective study.

Interleukin 7 receptor (IL7R) is vital in the adaptive immune response against human immunodeficiency viruses (HIV). We assessed IL7RA polymorphisms (SNPs) in antiretroviral therapy (ART)-naïve HIV patients for their association with spontaneous HIV infection control. We conducted a retrospective cohort study involving 667 ART-naïve patients categorized by HIV progression (ordinal variable): 150 rapid progressors, 334 moderate/typical progressors, 86 long-term nonprogressors elite controllers (LTNPs-EC), and 97 LTNPs-non-EC. We genotyped three IL7RA SNPs using Agena Bioscience's MassARRAY platform. The association between IL7RA SNPs and spontaneous HIV infection control was evaluated using ordinal logistic regression. Individuals carrying the rs10491434 G allele have a higher likelihood of spontaneous HIV infection control (adjusted odds ratio [aOR] = 1.33; p = 0.023). Moreover, the IL7RA GCT haplotype, consisting of three specific SNPs (rs6897932, rs987106, and rs10491434), demonstrated an association with the control of untreated HIV infection (aOR = 1.34; p = 0.050). Remarkably, the rs10491434 SNP and the IL7RA GCT haplotype exhibited similar aOR values, suggesting that rs10491434 may be primarily responsible for the observed effect of the haplotype. IL7RA rs10491434 G allele is associated with a higher likelihood of spontaneous HIV infection control, indicating its significant role in the pathogenesis of HIV, possibly influencing infection course and viral replication control.

Isolation and characterization of two glycolipopeptids biosurfactants produced by a Lactiplantibacillus plantarum OL5 strain isolated from green olive curing water.

Microbial surfactants are natural amphiphilic compounds with high surface activities and emulsifying properties. Due to their structural diversity, low toxicity, biodegradability, and chemical stability in different conditions, these molecules are potential substitutes for chemical surfactants; their interest has grown significantly over the last decade. The current study focuses on the isolation, identification, and characterization of a lactic acid bacteria that produce two forms of biosurfactants. The OL5 strain was isolated from green olive fermentation and identified using MALDI/TOF and DNAr16S amplification. Emulsification activity and surface tension measurements were used to estimate biosurfactant production. The two biosurfactants derived from Lactiplantibacillus plantarum OL5 presented good emulsification powers in the presence of various oils. They were also shown to have the potential to reduce water surface tension from 69 mN/m to 34 mN/m and 37 mN/m within a critical micelle concentration (CMC) of 7 mg/ml and 1.8 mg/ml, respectively, for cell bound and extracellular biosurfactants. Thin layer chromatography (TLC) and FT-IR were used to analyze the composition of the two biosurfactants produced. the obtained data revealed that the two biomolecules consist of a mixture of carbohydrates, lipids and proteins. We demonstrated that they are two anionic biosurfactants with glycolipopeptide nature which are stable in extreme conditions of temperature, pH and salinity.

IRF5-TNOP3 polymorphisms are associated with elite control of HIV infection: A retrospective study.

IRF5-TNPO3 polymorphisms have previously been related to immune response, and TNPO3 plays a role in human immunodeficiency virus (HIV)-1 infection after nuclear import. Therefore, we analyzed the genetic association between IRF5-TNPO3 polymorphisms and the HIV elite control in long-term nonprogressors (LTNPs). We performed a retrospective cohort study on 183 LTNPs, who were antiretroviral therapy-naïve with CD4+ ≥ 500 cells/mm3 , viral load ≤10 000 copies/mL, and asymptomatic over 10 years after HIV seroconversion. The primary outcome variable was HIV elite control (undetectable viral load in at least 90% of the measurements for at least 1 year). Seven IRF5-TNPO3 polymorphisms were genotyped using Agena Bioscience's MassARRAY platform. We found a significant association between specific IRF5-TNPO3 genotypes and HIV elite control: rs2004640 TT (aOR = 2.05; p = 0.041), rs10954213 AA (aOR = 1.95; p = 0.035), rs2280714 TT (aOR = 2.02; p = 0.031), and rs10279821 CC (aOR = 2.12; p = 0.017). We also found a significant association between IRF5-TNPO3 haplotype TATC composed of the favorable significant polymorphisms (rs2004640, rs10954213, rs2280714, and rs10279821) and the HIV elite control (aOR = 1.59; p = 0.048). IRF5-TNPO3 rs2004640, rs10954213, rs2280714, and rs10279821 polymorphisms were related to HIV elite control in LTNPs. Our data provide new knowledge about the impact of IRF5-TNPO3 polymorphisms on HIV pathogenesis to understand the phenomenon of natural HIV control.

Neutrophil ß1 adrenoceptor blockade blunts stroke-associated neuroinflammation.

BACKGROUND AND PURPOSE: Reperfusion therapy is the standard of care for ischaemic stroke; however, there is a need to identify new therapeutic targets able to ameliorate cerebral damage. Neutrophil ß1 adrenoceptors (ß1AR) have been linked to neutrophil migration during exacerbated inflammation. Given the central role of neutrophils in cerebral damage during stroke, we hypothesize that ß1AR blockade will improve stroke outcomes. EXPERIMENTAL APPROACH: Rats were subjected to middle cerebral artery occlusion-reperfusion to evaluate the effect on stroke of the selective ß1AR blocker metoprolol (12.5 mg·kg-1 ) when injected i.v. 10 min before reperfusion. KEY RESULTS: Magnetic resonance imaging and histopathology analysis showed that pre-reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24 h and vasogenic oedema at 7 days. Metoprolol-treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti-inflammatory phenotype (N2, YM1+ ). Additional inflammatory models demonstrated that metoprolol specifically blocked neutrophil migration via ß1AR and excluded a significant effect on the glia compartment. Consistently, metoprolol did not protect the brain in neutrophil-depleted rats upon stroke. In patients suffering an ischaemic stroke, ß1AR blockade by metoprolol reduced circulating neutrophil-platelet co-aggregates. CONCLUSIONS AND IMPLICATIONS: Our findings describe that ß1AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored.

High frequency of CD8 escape mutations in elite controllers as new obstacle for HIV cure.

Accumulation of mutations in epitopes of cytolytic-T-lymphocytes immune response (CTL) in HIV-reservoir seems to be one of the reasons for shock-and-kill strategy failure. Ten non-controller patients on successful cART (TX) and seven elite controllers (EC) were included. HIV-Gag gene from purified resting memory CD4+ T-cells was sequenced by Next-Generation-Sequencing. HLA class-I alleles were typed to predict optimal HIV-Gag CTL epitopes. For each subject, the frequency of mutated epitopes in the HIV-Gag gene, the proportion of them considered as CTL-escape variants as well as their effect on antigen recognition by HLA were assessed. The proportion (%) of mutated HIV-Gag CTL epitopes in the reservoir was high and similar in EC and TX (86%[50-100] and 57%[48-82] respectively, p=0.315). Many of them were predicted to negatively impact antigen recognition. Moreover, the proportion of mutated epitopes considered to be CTL-escape variants was also similar in TX and EC (77%[49-92] vs. 50%[33-75] respectively, p=0.117). Thus, the most relevant finding of our study was the high and similar proportions of HIV-Gag CTL-escape mutations in the reservoir of both HIV-noncontroller patients with cART (TX) and patients with spontaneous HIV-control (EC). Our findings suggest that escape mutations of CTL-response may be another obstacle to eliminate the HIV reservoir and constitute a proof of concept that challenges HIV cure strategies focused on the reactivation of reservoirs. Due to the small sample size that could impact the robustness of the study, further studies with larger cohorts of elite controller patients are needed to confirm these results.

Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control.

Long-term elite controllers (LTECs) are a fascinating small subset of HIV individuals with viral and immunological HIV control in the long term that have been designated as models of an HIV functional cure. However, data on the LTEC phenotype are still scarce, and hence, the metabolomics and lipidomics signatures in the LTEC-extreme phenotype, LTECs with more than 10 years of viral and immunological HIV control, could be pivotal to finding the keys for functional HIV remission. Metabolomics and lipidomics analyses were performed using high-resolution mass spectrometry (ultra-high-performance liquid chromatography-electrospray ionization-quadrupole time of flight [UHPLC-(ESI) qTOF] in plasma samples of 13 patients defined as LTEC-extreme, a group of 20 LTECs that lost viral and/or immunological control during the follow-up study (LTEC-losing) and 9 EC patients with short-term viral and immunological control (less than 5 years; no-LTEC patients). Long-term viral and immunological HIV-1 control was found to be strongly associated with elevated tricarboxylic acid (TCA) cycle function. Interestingly, of the nine metabolites identified in the TCA cycle, α-ketoglutaric acid (p = 0.004), a metabolite implicated in the activation of the mTOR complex, a modulator of HIV latency and regulator of several biological processes, was found to be a key metabolite in the persistent control. On the other hand, a lipidomics panel combining 45 lipid species showed an optimal percentage of separation and an ability to differentiate LTEC-extreme from LTEC-losing, revealing that an elevated lipidomics plasma profile could be a predictive factor for the reignition of viral replication in LTEC individuals.

High Plasma sTNF-R1 Level Is Related to Loss of Natural HIV Control in Long-Term Elite Controllers.

Human immunodeficiency virus-1 (HIV-1) elite controllers are heterogeneous due to different immunovirological features. We aimed to identify plasma biomarkers associated with loss of spontaneous HIV-1 control in long-term elite controllers (HIV-LTECs). We performed a retrospective study in 60 HIV-LTECs [36 true-LTECs and 24 LTECs losing control (LTECs-LC)]. We selected a plasma sample from true-LTECs (towards the middle of the follow-up period) and two samples from LTECs-LC (one far from the loss of control and another close to loss of control). Plasma biomarkers were evaluated using multiplex immunoassays. The partial least squares-discriminant analysis provided the variable importance in projection (VIP), and the adjusted Generalized Linear Model provided the adjusted arithmetic mean ratio (aAMR). At the moment of the first LTECs-LC samples, the only plasma biomarker with a VIP≥1.5 was sTNF-R1, which showed higher values in LTECs-LC than true-LTECs [aAMR=1.62 (95%CI=1.20-2.19); p=0.001]. After a median of 3.9 (IQR=4.5) years of follow-up from the first sample, we also had access to a second plasma sample from 10 LTECs-LC patients. At the moment of this second LTECs-LC sample, the only plasma biomarker with VIP≥1.5 was also sTNF-R1, which showed higher values in LTECs-LC than true-LTECs [aAMR=1.93 (95%CI=1.41-2.65); p<0.001]. The difference between the first and second samples of LTECs-LC was significant (Δx= 6.58 (95%=0.3; 12.88); p=0.040). In conclusion, high plasma values of sTNF-R1 appear to discriminate HIV-LTECs that lose the natural control of HIV-1, helping to define a specific phenotype that may be useful for the clinical management of these patients.

Initiation of antiretroviral therapy in treatment-naive adults with HIV infection at the first specialist appointment.

BACKGROUND: Fast initiation of ART has been associated with higher rates of retention in HIV care and viral suppression at 48 weeks and with lower mortality rates. However, scarce evidence exists in our setting, where diagnosis and treatment are carried out in different contexts. METHODS: An observational retrospective study evaluating efficacy and safety of ART prescribed at the first specialist appointment, without baseline laboratory data, in a tertiary hospital in downtown Madrid. Individuals with a new diagnosis of HIV infection who initiated treatment at their first appointment with an infectious diseases specialist before receiving baseline laboratory results were included, irrespective of the ART regimen chosen. RESULTS: One hundred and eight participants were included. The majority (99.1%) were MSM who had acquired infection during sexual intercourse. The efficacy of ART, without baseline laboratory results at the time of initiation, was 85.2% (92/108) in the ITT analysis and 91.7% (99/108) in the treatment-related discontinuation equals failure analysis. All but nine patients presented an undetectable viral load (<50 copies/mL) at 48 weeks from starting ART. No serious adverse effects associated with the strategy were observed. In total, 101 participants continued care at 48 weeks with retention in HIV care rate of 93.5% (101/108). CONCLUSIONS: Initiating ART at the first available opportunity without baseline laboratory data does not reduce efficacy or safety of ART and achieves rapid virological control with high rates of retention in HIV care.

HIV-reservoir size is not affected either by HCV coinfection or by direct acting antivirals (DAAs) therapy.

The role of HCV on the HIV reservoir is controversial since the reduction on HIV-DNA levels after HCV eradication with IFNα/RBV treatment seems to be the result of drugs instead of HCV clearance. We assessed whether HCV eradication can decrease HIV-DNA content in HIV/HCV-coinfected patients treated with direct-acting antivirals, DAAs (IFNα/RBV-free regimens). Cell-associated HIV-DNA was measured by ddPCR in 25 HIV-monoinfected and 25 HIV/HCV-coinfected patients. There were no differences in HIV-DNA levels between groups neither at baseline nor at 12 weeks after DAAs treatment completion. Our results indicate that HCV does not appear to influence the HIV reservoir size and suggest the lack of an anti-HIV action for DAAs.

Preparation of Water-in-Oil Nanoemulsions Loaded with Phenolic-Rich Olive Cake Extract Using Response Surface Methodology Approach.

In this study, we aimed to prepare stable water-in-oil (W/O) nanoemulsions loaded with a phenolic-rich aqueous phase from olive cake extract by applying the response surface methodology and using two methods: rotor-stator mixing and ultrasonic homogenization. The optimal nanoemulsion formulation was 7.4% (w/w) of olive cake extract as the dispersed phase, and 11.2% (w/w) of a surfactant mixture of polyglycerol polyricinoleate (97%) and Tween 80 (3%) in Miglyol oil as the continuous phase. Optimum results were obtained by ultrasonication for 15 min at 20% amplitude, yielding W/O nanoemulsion droplets of 104.9 ± 6.7 nm in diameter and with a polydispersity index (PDI) of 0.156 ± 0.085. Furthermore, an optimal nanoemulsion with a droplet size of 105.8 ± 10.3 nm and a PDI of 0.255 ± 0.045 was prepared using a rotor-stator mixer for 10.1 min at 20,000 rpm. High levels of retention of antioxidant activity (90.2%) and phenolics (83.1-87.2%) were reached after 30 days of storage at room temperature. Both W/O nanoemulsions showed good physical stability during this storage period.

Encapsulation of Pomegranate Peel Extract (Punica granatum L.) by Double Emulsions: Effect of the Encapsulation Method and Oil Phase.

Pomegranate peel is an agro-industrial waste that can be used as source of punicalagin, a polyphenolic compound with several beneficial effects on health. Since, once extracted, punicalagin is prone to degradation, its encapsulation by double emulsions can be an alternative to protect the active compound and control its release. The aim of this investigation was to evaluate the feasibility of encapsulating pomegranate peel extract (PPE) in double emulsions using different types of oils (castor, soybean, sunflower, Miglyol and orange) in a ratio of 70:30 (oil:PPE) and emulsification methods (direct membrane emulsification and mechanical agitation), using polyglycerol polyricinoleate (PGPR) and Tween 80 as lipophilic and hydrophilic emulsifiers, respectively. Direct membrane emulsification (DME) led to more stable emulsions during storage. Droplet size, span values, morphology and encapsulation efficiency (EE) were better for double emulsions (DEs) prepared by DME than for mechanical agitation (MA). DEs formulated using Miglyol or sunflower oil as the oily phase could be considered as suitable food grade systems to encapsulate punicalagin with concentrations up to 11,000 mg/L of PPE.

Cellular and humoral functional responses after BNT162b2 mRNA vaccination differ longitudinally between naive and subjects recovered from COVID-19.

We have analyzed BNT162b2 vaccine-induced immune responses in naive subjects and individuals recovered from coronavirus disease 2019 (COVID-19), both soon after (14 days) and later after (almost 8 months) vaccination. Plasma spike (S)-specific immunoglobulins peak after one vaccine shot in individuals recovered from COVID-19, while a second dose is needed in naive subjects, although the latter group shows reduced levels all along the analyzed period. Despite how the neutralization capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mirrors this behavior early after vaccination, both groups show comparable neutralizing antibodies and S-specific B cell levels late post-vaccination. When studying cellular responses, naive individuals exhibit higher SARS-CoV-2-specific cytokine production, CD4+ T cell activation, and proliferation than do individuals recovered from COVID-19, with patent inverse correlations between humoral and cellular variables early post-vaccination. However, almost 8 months post-vaccination, SARS-CoV-2-specific responses are comparable between both groups. Our data indicate that a previous history of COVID-19 differentially determines the functional T and B cell-mediated responses to BNT162b2 vaccination over time.

Adherence to a Supplemented Mediterranean Diet Drives Changes in the Gut Microbiota of HIV-1-Infected Individuals.

OBJECTIVE: The health effects of a supplemented Mediterranean diet (SMD) with extra-virgin olive oil (EVOO) and nuts are well documented in non-HIV-infected individuals. We hypothesised that the benefits of an SMD could be mediated by changes in the gut microbiota, even in those with an altered intestinal microbiota such as people living with HIV. DESIGN: Individuals living with HIV (n = 102) were randomised to receive an SMD with 50 g/day of EVOO and 30 g/day of walnuts (SMD group) or continue with their regular diet (control group) for 12 weeks. METHODS: Adherence to the Mediterranean diet was assessed using the validated 14-item MD-Adherence-Screener (MEDAS) from the PREDIMED study. A sub-study classifying the participants according to their MEDAS scores was performed. RESULTS: The lipid profile was improved in the SMD group vs. that in the control group (delta-total cholesterol and delta-B-lipoprotein). The immune activation (CD4+HLADR+CD38+ and CD8+HLADR+CD38+ cells) and IFN-γ-producing T-cells significantly decreased at week 12 compared to the baseline in the SMD group but not in the control group. The gut microbiota in those from the high-adherence group presented significantly high diversity and richness at the end of the intervention. Succinivibrio and Bifidobacterium abundances were influenced by the adherence to the MD and significantly correlated with Treg cells. CONCLUSION: The Mediterranean diet improved metabolic parameters, immune activation, Treg function, and the gut microbiota composition in HIV-1-infected individuals. Further, Mediterranean diet increased the Bifidobacterium abundances after the intervention, and it was associated to a beneficial profile.

HIV-DNA content in pTfh cells is associated with residual viremia in elite controllers.

OBJECTIVE: The source of residual HIV viremia is highly debated and its potential relationship with the HIV reservoir has not been clarified. Herein, we analysed the cell-associated HIV-DNA content in two important cell compartments of the HIV reservoir, resting CD4+ T memory (Trm) and peripheral T follicular helper (pTfh) cells, and the association with the residual HIV viremia in individuals with spontaneous HIV replication control (elite controllers, EC group) and in individuals with antiretroviral therapy (ART)-mediated HIV replication control (cART group). DESIGN: A cross-sectional study. METHODS: Seventeen chronically HIV-infected patients with suppressed HIV replication were included. Cell-associated HIV-DNA was measured by ultrasensitive digital-droplet-PCR in purified Trm and pTfh cells. Residual HIV plasma viremia was quantified using a single-copy assay with a sensitivity of 0.3 HIV-RNA copies/ml. RESULTS: A significant and positive correlation was demonstrated between HIV-DNA levels in pTfh cells and residual plasma viral load (rpVL) (rho = 0.928, P = 0.008) in HIV-positive elite controllers, but not in HIV-positive treated patients, despite the lower levels of cell-associated HIV-DNA found in elite controllers compared with cART patients in pTfh cells [176 (77-882) vs. 608 (361-860) copies/million cells, respectively; P = 0.05]. CONCLUSION: This association suggests that pTfh cells could have an important contribution to persistent viremia in elite controllers. This could be the consequence of a more limited control of HIV replication in elite controllers with higher transcriptional activity of HIV in pTfh cells of elite controllers than that in cART patients.

DBP rs7041 and DHCR7 rs3829251 are Linked to CD4+ Recovery in HIV Patients on Antiretroviral Therapy.

Background: The lack of the recovery of CD4+ T-cells (CD4+ recovery) among immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART) is not well known. We aimed to analyze the association between single nucleotide polymorphisms (SNPs) underlying vitamin D metabolism and the CD4+ recovery in naïve HIV-infected patients who started ART with low baseline CD4+. Methods: We conducted a retrospective study in 411 naïve individuals with plasma HIV load >200 copies/mL and CD4+ <200 cells/mm3. During 24 months of follow-up, all patients had plasma HIV load <50 copies/mL. DNA genotyping was performed using the Sequenom MassARRAY platform. The outcome variable was the change in CD4+ during the study. Results: CD4+ recovery was higher in patients carrying DBP rs7041 AA genotype (AA versus CC/AC) and DHCR7 rs3829251 AA genotype (AA versus GG/AG) (p-value < 0.05). DBP rs7041 AA genotype was linked to increase in CD4+ (adjusted arithmetic mean ratio (aAMR) = 1.22; q-value = 0.011), increase in CD4+ ≥P75th [adjusted odds ratio (aOR) = 2.31; q-value = 0.005], slope of CD4+ recovery (aAMR = 1.25; q-value = 0.008), slope of CD4+ recovery ≥ P75th (aOR = 2.55; q-value = 0.005) and achievement of CD4+ ≥500 cells/mm3 (aOR = 1.89; q-value = 0.023). Besides, DHCR7 rs3829251 AA genotype was related to increase in CD4+ (aAMR = 1.43; q-value = 0.031), increase in CD4+ ≥P75th (aOR = 3.92; q-value = 0.030), slope of CD4+ recovery (aAMR = 1.40; q-value = 0.036), slope of CD4+ recovery ≥ P75th (aOR = 3.42; q-value = 0.031) and achievement of CD4+ ≥500 cells/mm3 (aOR = 5.68; q-value = 0.015). Conclusion: In summary, DHCR7 rs3829251 and DBP rs7041 polymorphisms were associated with CD4+ recovery in HIV-infected patients who started cART with low CD4+ T-cell counts.

Extracellular Vesicles as a New Promising Therapy in HIV Infection.

Combination antiretroviral therapy (cART) effectively blocks HIV replication but cannot completely eliminate HIV from the body mainly due to establishment of a viral reservoir. To date, clinical strategies designed to replace cART for life and alternatively to eliminate the HIV reservoir have failed. The reduced expression of viral antigens in the latently infected cells is one of the main reasons behind the failure of the strategies to purge the HIV reservoir. This situation has forced the scientific community to search alternative therapeutic strategies to control HIV infection. In this regard, recent findings have pointed out extracellular vesicles as therapeutic agents with enormous potential to control HIV infection. This review focuses on their role as pro-viral and anti-viral factors, as well as their potential therapeutic applications.

COVID-19 in people living with HIV: A multicenter case-series study.

OBJECTIVES: Information on how COVID-19 affects people living with HIV (PLHIV) remains scarce. METHODS: An observational study was conducted in four public hospitals in Madrid. All HIV patients with confirmed or suspected COVID-19 were included and compared with COVID-19 patients without HIV infection. RESULTS: Sixty-three patients with HIV infection and confirmed or suspected COVID-19 were analyzed. The median age was 46 years (IQR: 37-56 years), and 88.9% were men. The median duration of HIV infection was 10.8 years (IQR: 6.5-16.8 years), and 96.8% were on antiretroviral therapy. 84.1% had previous comorbidities. The most common symptoms were fever (66.1%), cough (66.1%) and dyspnea (46.8%). Pneumonia was found in 47.5%, 28.6% of patients had severe disease, and 32.3% were admitted to hospital. The ICU admission rate and the mortality rate were both 3.17%. A significant association was observed between age, arterial hypertension, overweight, and diabetes mellitus and the severity of COVID-19. No association was observed between HIV-related factors and the severity of COVID-19. The rate of COVID-19 in HIV-patients was 1.68%. Similar hospitalization (31.74% vs 32.57%) and ICU admission (3.17% vs 2%) rates were observed with non-HIV infected patients. A lower mortality rate during hospitalization (10% vs 21.37%) and a lower global mortality rate (3.17% vs 6.96%) were also observed. CONCLUSIONS: Established poor prognostic factors for COVID-19 patients, such as age and comorbidities, remain the main determinants for PLHIV. Neither the HIV severity nor the type of ARV treatment seem to influence the outcome of COVID-19. Large prospective cohorts are needed in order to establish the differences between HIV-positive and HIV-negative patients.

Formulation and Preparation of Water-In-Oil-In-Water Emulsions Loaded with a Phenolic-Rich Inner Aqueous Phase by Application of High Energy Emulsification Methods.

Currently, industry is requesting proven techniques that allow the use of encapsulated polyphenols, rather than free molecules, to improve their stability and bioavailability. Response surface methodology (RSM) was applied in this work to determine the optimal composition and operating conditions for preparation of water-in-oil-in-water (W/O/W) emulsions loaded with phenolic rich inner aqueous phase from olive mill wastewater. A rotor-stator mixer, an ultrasonic homogenizer and a microfluidizer processor were tested in this study as high-energy emulsification methods. Optimum results were obtained by means of microfluidizer with 148 MPa and seven cycles input levels yielding droplets of 105.3 ± 3.2 nm in average size and 0.233 ± 0.020 of polydispersity index. ζ-potential, chemical and physical stability of the optimal W/O/W emulsion were also evaluated after storage. No droplet size growth or changes in stability and ζ-potential were observed. Furthermore, a satisfactory level of phenolics retention (68.6%) and antioxidant activity (89.5%) after 35 days of storage at room temperature makes it suitable for application in the food industry.

Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected Patients.

(1) Background: The role of hepatitis C virus (HCV) co-infection on the T-cell homeostasis disturbances in human immunodeficiency virus (HIV)-infected patients as well as its reversion after HCV eradication with direct acting antivirals (DAAs) therapy has not been yet clarified. We extensively analyzed the effect of HCV co-infection on immune parameters of HIV pathogenesis and its evolution after HCV eradication with DAAs. (2) Methods: Seventy individuals were included in the study-25 HIV-monoinfected patients, 25 HIV/HCV-coinfected patients and 20 HIV and HCV seronegative subjects. All patients were on antiretroviral therapy and undetectable HIV-viremia. Immune parameters, such as maturation, activation, apoptosis, senescence and exhaustion of T-cells were assessed by flow cytometry. Cross-sectional and longitudinal (comparing pre- and post-DAAs data in HIV/HCV coinfected patients) analyses were performed. Univariate and multivariate (general linear model and canonical discriminant analysis -CDA-) analyses were used to assess differences between groups. (3) Results-The CDA was able to clearly separate HIV/HCV coinfected from HIV-monoinfected patients, showing a more disturbed T-cells homeostasis in HIV/HCV patients, especially activation and exhaustion of T-cells. Interestingly, those perturbations were more marked in HIV/HCV patients with increased liver stiffness. Eradication of HCV with DAAs restored some but not all the T-cells homeostasis disturbances, with activation and exhaustion of effector CD8 T-cells remaining significantly increased three months after HCV eradication. (4) Conclusions-HCV co-infection significantly impacts on several immune markers of HIV pathogenesis, especially in patients with increased liver stiffness. Eradication of HCV with DAAs ameliorates but does not completely normalize these alterations. It is of utmost relevance to explore other mechanisms underlying the immune damage observed in HIV/HCV coinfected patients with control of both HIV and HCV replication.