No impact of HIV coinfection on the mortality in patients with hepatitis C virus infection after sustained virological response.

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) ≥9.5 kPa before treatment; 2) SVR with a direct-acting antiviral (DAA) based regimen; 3) LS measurement available at SVR. The main outcome was overall survival. Mortality attributable to liver disease and non-hepatic causes was also assessed. RESULTS: 1,118 patients were included, of whom 676 (60.5%) were living with HIV. The median (Q1-Q3) follow-up was 76 months (57-83). After SVR, 46 (10%) HCV-monoinfected and 74 (11%) HIV/HCV-coinfected patients died. The overall mortality rate (95% CI) was 1.9 (1.6-2.2) per 100 person-years, 1.9 (1.4-2.5) per 100 person-years in patients with HCV-monoinfection and 1.8 (1.6-2.3) per 100 person-years in people living with HIV. In the multivariable analysis, HIV-coinfection was not associated with a shorter survival [0.98 HR (95% confidence interval, CI) = (0.61-1.58), p=0.939]. CONCLUSIONS: In patients with HCV chronic infection and advanced fibrosis, HIV-coinfection does not reduce the overall survival after SVR.

Long or complicated mpox in patients with uncontrolled HIV infection.

To date, former research about the impact of HIV infection on mpox poor outcomes is still limited and controversial. Therefore, the aim of this study was to assess the impact of HIV on the clinical course of mpox, in a large population of patients from Spain. Nationwide case-series study. Patients from 18 Spanish hospitals, with PCR-confirmed mpox from April 27, 2022 to June 30, 2023 were included in this study. The main outcome was the development of long or complicated (LC) mpox, defined as: (i) duration of the clinical course ≥ 28 days, or; (ii) disseminated disease, or: (iii) emergence of severe complications. One thousand eight hundred twenty-three individuals were included. Seven hundred eighty-six (43%) were people living with HIV (PLWH), of whom 11 (1%) had a CD4 cell count < 200 cells/mm3 and 33 (3%) <350 cells/mm3 . HIV viral load ≥ 1000 cp/mL was found in 27 (3%) PLWH, none of them were on effective ART. Fifteen (60%) PLWH with HIV-RNA ≥ 1000 cp/mL showed LC versus 182 (29%) PLWH with plasma HIV-RNA load < 1000 copies/mL and 192 (24%) individuals without HIV infection (p < 0.001). In multivariate analysis, adjusted by age, sex, CD4 cell counts and HIV viral load at the time of mpox, only plasma HIV-RNA ≥ 1000 cp/mL was associated with a greater risk of developing LC mpox [adjusted OR = 4.06 (95% confidence interval 1.57-10.51), p = 0.004]. PLWH with uncontrolled HIV infection, due to lack of ART, are at a greater risk of developing LC mpox. Efforts should be made to ensure HIV testing is carried out in patients with mpox and to start ART without delay in those tested positive.

Response to glecaprevir/pibrentasvir in HIV/HCV-coinfected patients in clinical practice.

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. Patients starting G/P included in those cohorts were analysed. Overall SVR (ITT), discontinuations due to adverse effects, and dropouts were evaluated and compared between both cohorts. RESULTS: Of the 644 patients who started G/P with evaluable SVR, 132 were HIV/HCV coinfected. Overall SVR rates were 487/512 (95.1%) in HCV-monoinfected patients versus 126/132 (95.5%) in HIV/HCV-coinfected patients (P = 1.000). One patient (0.8%) relapsed, and another (0.8%) discontinued treatment due to side effects. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected versus HCV-monoinfected patients. The main reason for not reaching SVR among HIV/HCV-coinfected patients was premature dropout linked to active drug use. CONCLUSIONS: G/P in HIV/HCV coinfection was highly effective and tolerable in clinical practice. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected compared with HCV-monoinfected patients but active drug use is still a barrier to reach HCV microelimination.

Reduced neutralizing antibody response to SARS-CoV-2 vaccine booster dose in people living with HIV with severe immunosuppression.

The aim of this study was to assess the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among people living with HIV (PLWH) with severe immunosuppression, after a booster dose. The design was a case-control study nested in a prospective cohort of PLWH. All patients with CD4 cell count <200 cells/mm3 who had received additional dose of messenger RNA (mRNA) COVID-19 vaccine, after a standard immunization scheme were included. Control group: patients age- and sex-matched, with CD4 ≥ 200 cells/mm3 , in the ratio of 2:1. Antibody response to a booster dose (anti-S levels 33.8 ≥ BAU/mL) and neutralizing activity against SARS-CoV-2 B.1, B.1.617.2, and Omicron BA.1, BA.2, and BA.5 strains were assessed after the booster shot. Fifty-four PLWH were included, 18 with CD4 counts < 200 cells/mm3 . Fifty-one (94%) showed response to a booster dose. Response was less frequent in PLWH with CD4 < 200 cells/mm3 than in those with CD4 counts ≥ 200 cells/mm3 (15 [83%] vs. 36 [100%], p = 0.033). In the multivariate analysis, CD4 counts ≥ 200 cells/mm3 [incidence rate ratio (IRR) = 18.1 (95% confidence interval [CI]: 16.8-19.5), p < 0.001] was associated with a higher probability of showing antibody response. Neutralization activity against SARS-CoV-2 B.1, B.1.617, BA.1, and BA.2 strains was significantly inferior among individuals with CD4 counts < 200 cells/mm3 . In conclusion, among PLWH with CD4 counts < 200 cells/mm3 , the immune response elicited by mRNA additional vaccine dose is reduced.

Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients.

BACKGROUND AND AIMS: People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. METHODS: We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). RESULTS: We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. CONCLUSIONS: Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone.

Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower Risk of Hepatocellular Carcinoma After Sustained Virological Response to Direct-acting Antivirals in Hepatitis C Infected Patients With Advanced Fibrosis.

BACKGROUND: The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA). METHODS: Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients. RESULTS: In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1-Q3) follow-up time of 43 (31-49) months, 19 (1.8%) patients developed HCC (11 [3.0%]; HCV-monoinfected, 8[1.2%]; HIV/HCV-coinfected individuals; P = .013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio [sHR] = 0.27, 95% confidence interval [CI]: .08-.90; P = .034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5-24.9; P < .001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01-1.86; P = .043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01-1.06, for 1 kPa increase; P = .011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI: .11-.85). CONCLUSIONS: Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated.

Liver Stiffness-Based Strategies Predict Absence of Variceal Bleeding in Cirrhotic Hepatitis C Virus-Infected Patients With and Without Human Immunodeficiency Virus Coinfection After Sustained Virological Response.

BACKGROUND: In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited. METHODS: This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral-based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed. RESULTS: Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval [CI], 97.1%-100%), 100% (95% CI 97.8%-100%), and 100% (95% CI 98%-100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals. CONCLUSIONS: After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.

A genome-wide association study on low susceptibility to hepatitis C virus infection (GEHEP012 study).

BACKGROUND: A low proportion of individuals repeatedly exposed to the hepatitis C virus (HCV) remain uninfected. This condition could have a genetic basis but it is not known whether or not it is mainly driven by a high-penetrance common allele. OBJECTIVE: To explore whether low susceptibility to HCV infection is mainly driven by a high-penetrance common allele. METHODS: In this genome-wide association study (GWAS), a total of 804 HCV-seropositive individuals and 27 high-risk HCV-seronegative (HRSN) subjects were included. Plink and Magma software were used to carry out single nucleotide polymorphism (SNP)-based and gene-based association analyses respectively. RESULTS: No SNP nor any gene was associated with low susceptibility to HCV infection after multiple testing correction. However, SNPs previously associated with this trait and allocated within the LDLR gene, rs5925 and rs688, were also associated with this condition in our study under a dominant model (24 out of 27 [88.9%] rs5925-C carriers in the HRSN group vs 560 of 804 [69.6%] rs5925-C carriers in the HCV-seropositive group, P = 0.031, odds ratio [OR] = 3.48; 95% confidence interval [CI] = 1.04-11.58; and 24 out of 27 [88.9%] rs688-T carriers in the HRSN group vs 556 of 804 [69.1%] rs688-T carriers in the HCV-seropositive group, P = 0.028, OR = 3.57, 95% CI = 1.65-11.96). CONCLUSIONS: Low susceptibility to HCV infection does not seem to be mainly driven by a high-penetrant common allele. By contrast, it seems a multifactorial trait where genes such as LDLR could be involved.

The absence of seroconversion after exposition to hepatitis C virus is not related to KIR-HLA genotype combinations (GEHEP-012 study).

BACKGROUND & AIMS: It has been reported that specific killer-cell immunoglobulin-like receptors (KIRs) and HLA genotype combinations, such as KIR2DS4/HLA-C1 with presence of KIRDL2 or KIRDL3, homozygous KIRDL3/HLA-C1 and KIR3DL1/≥2HLA-Bw4, are strongly associated with the lack of active infection and seroconversion after exposition to hepatitis C virus (HCV). OBJECTIVE: To determine whether these KIR-HLA combinations are relevant factors involved in that phenotype. PATIENTS AND METHODS: In this retrospective case-control study, genotype data from a genome-wide association study previously performed on low susceptibility to HCV-infection carried out on 27 high-risk HCV-seronegative (HRSN) individuals and 743 chronically infected (CI) subjects were used. HLA alleles were imputed using R package HIBAG v1.2223 and KIR genotypes were imputed using the online resource KIR*IMP v1.2.0. RESULTS: It was possible to successfully impute at least one KIR-HLA genotype combination previously associated with the lack of infection and seroconversion after exposition to HCV in a total of 23 (85.2%) HRSN individuals and in 650 (87.5%) CI subjects. No KIR-HLA genotype combination analyzed was related to the HRSN condition. CONCLUSIONS: Our results suggest that those KIR-HLA genotype combinations are not relevant factors involved in the lack of infection and seroconversion after exposition to HCV. More studies will be needed to completely understand this phenotype.

Hepatic steatosis after switching to integrase inhibitor-based regimens does not parallel short-term weight gain.

We studied hepatic steatosis in people with HIV (PWH) who switched to an integrase inhibitor (INSTI)-based regimen. One hundred and fifty-four PWH were included. After 48 weeks, median (Q1-Q3) weight gain was 1.2 (-0.6 to 3.8) kg and median (Q1-Q3) controlled attenuation parameter (CAP) change was -4 (-33 to 27) dB/m. Weight gain was weakly correlated with CAP change [R2 95% confidence interval (CI) = 0.144 (-0.014 to 0.296); P = 0.074)]. Changes in hepatic steatosis after switching to INSTI-based regimens do not seem to parallel weight gain after 1 year.

Poor increase on HAV vaccination coverage among people living with HIV after an immunization-based intervention.

OBJECTIVES: To assess HAV serologic and vaccination status among people who live with HIV (PLWH), and to evaluate the impact of a vaccination-based strategy on HAV-negative patients in Seville, Spain. METHODS: Study with two time-overlapping phases: (i) cross-sectional study of HAV immunity prevalence among PLWH followed at a Spanish hospital between August 2019 and March 2020. (ii) Patients seronegative for HAV, reliably unvaccinated were included in a before-and-after quasi-experimental study, with an intervention focused on HAV vaccination according to national recommendations in force. RESULTS: Six hundred and fifty-six patients were included, of which 111 [17%, 95% confidence interval (95% CI) 14-20%] were seronegative for HAV. Of these, 48 [43% (95% CI, 34-53%)] individuals were MSM. The absence of HAV immunity was attributed in 69 [62% (95% CI, 52-71%)] patients to non-referral to vaccination, followed by lack of achievement of a correct vaccination scheme [n=26; 23% (95% CI, 16-32%)]. After the program implementation, 96 [15% (95% CI, 12-18%)] individuals were seronegative (17% vs. 15%, p=0.256), of whom 42 [41% (95% CI, 32-51%)] were MSM. The absence of immunity after the intervention was mainly attributed to: adherence failure in 23 [24.0% (95% CI, 15.8-33.7%)] patients, on-course immunization scheme in 34 [33% (95% CI, 24-43%)] individuals and pending appointment at the vaccine delivery unit in 20 [20.8% (95% CI, 13.2-30.3%)] patients. CONCLUSIONS: A sizeable proportion of PLWH remains susceptible for HAV infection in future outbreaks. A program based on referral to the vaccine delivery unit yields poor results, largely due to program adherence failures. New strategies are needed to increase HAV vaccination coverage.

Low rate of vaccination and risk of incident hepatitis A among HIV-infected men who have sex with men in Seville, Southern Spain.

BACKGROUND: Periodic outbreaks of hepatitis A (HAV) infection in men who have sex with men (MSM) have been reported. Low vaccination uptake in HIV-infected individuals could drive new outbreaks. We aimed at evaluating the incidence of and risk factors for HAV infection in people living with HIV (PLWH) in our area. We also assessed the rates of HAV vaccination. METHODS: This was a prospective cohort study. 915 patients were included, 272 (30%) of them were anti-HAV seronegative at baseline. RESULTS: Twenty-six (9.6%) susceptible individuals became infected. Incident cases peaked in 2009-2010 and 2017-2018. Incident HAV infection was independently associated with MSM [adjusted odds ratio (95% confidence ratio): 4.39 (1.35-14.27), p=0.014]. One hundred and five (38.6%) HAV seronegative patients were vaccinated, 21 (20%) of them did not respond, and one (1%) patient lost immunity against HAV. Four (29%) non-responders to vaccination showed incident HAV 5-9 years afterwards. CONCLUSIONS: The incidence of HAV infection in a cohort of well-controlled PLWH remains low and stable, with intermittent outbreaks involving mainly non-immunized MSM. A significant proportion of PLWH remain susceptible to HAV infection due to insufficient vaccine uptake and limited response to vaccination. Importantly, patients not responding to HAV vaccination continue at risk of infection.

Hepatic Steatosis and Weight Gain During the Coronavirus Disease 2019 Pandemic Among People With Human Immunodeficiency Virus: Impact of Therapy With Tenofovir Alafenamide.

Background: Lockdown due to the coronavirus disease 2019 (COVID-19) pandemic led to increases in weight in part of the population. Weight gain leads to hepatic steatosis (HS). Antiretroviral treatment could also influence HS in people with human immunodeficiency virus (PWH). The impact of lockdown on HS in PWH is unknown. The aim of this study was to analyze the changes in HS, as measured by the controlled attenuation parameter (CAP), during the COVID-19 pandemic in PWH. Methods: This was a cohort study that included PWH who attended a tertiary care center in southern Spain from January 2018 to December 2021. The CAP was evaluated by transient elastography. Only those who had a valid CAP before and after March 2020 were included. HS was defined as CAP ≥248 dB/m. Results: Six hundred eighty PWH were attended and 488 (71.8%) were included. Two hundred and fourteen (43.9%) had HS at baseline and 239 (49%) at the end of the follow-up (P = .036). The median change in CAP among PWH taking tenofovir alafenamide (TAF) was 8.5 (interquartile range [IQR], -24 to 46.3) dB/m versus -4 (IQR, -35 to 27) dB/m among PWH receiving TAF-free regimens (P = .003). After multivariate analysis, adjusted by sex and age, weight gain (adjusted odds ratio [AOR], 1.09 [95% confidence interval {CI}, 1.05-1.14]; P < .001), TAF therapy (AOR, 1.59 [95% CI, 1.07-2.35]; P = .021), plasma triglycerides (AOR, 1.01 [95% CI, 1-1.01]; P < .001), and fasting blood glucose (AOR, 1.01 [95% CI, 1-1.02]; P = .027) were associated with HS at the end of follow-up. Conclusions: The frequency of HS increased during the COVID-19 pandemic among PWH. TAF is associated with HS development, regardless of metabolic factors.

A metagenome-wide association study of HIV disease progression in HIV controllers.

Some HIV controllers experience immunologic progression with CD4+ T cell decline. We aimed to identify genetic factors associated with CD4+ T cell lost in HIV controllers. A total of 561 HIV controllers were included, 442 and 119 from the International HIV controllers Study Cohort and the Swiss HIV Cohort Study, respectively. No SNP or gene was associated with the long-term non-progressor HIV spontaneous control phenotype in the individual GWAS or in the meta-analysis. However, SNPs previously associated with natural HIV control linked to HLA-B (rs2395029 [p = 0.005; OR = 1.70], rs59440261 [p = 0.003; OR = 1.78]), MICA (rs112243036 [p = 0.011; OR = 1.45]), and PSORS1C1 loci (rs3815087 [p = 0.017; OR = 1.39]) showed nominal association with this phenotype. Genetic factors associated with the long-term HIV controllers without risk of immunologic progression are those previously related to the overall HIV controller phenotype.

High efficacy of glecaprevir/pibrentasvir for HCV-infected individuals with active drug use.

OBJECTIVES: Real world data on glecaprevir/pibrentasvir (G/P) among active drug users are scarce. We evaluated the sustained virological response (SVR) rates of G/P among individuals with and without active drug use in routine clinical practice. METHODS: Two ongoing prospective multicenter cohorts of individuals starting G/P were analyzed. Overall SVR intention-to-treat (ITT), discontinuations due to adverse effects and dropouts were evaluated. Results in patients with active, past and without active drug use were compared. RESULTS: Overall, 644 individuals started G/P and have reached the date of SVR evaluation. Of them, 613 (95.2%) individuals achieved SVR. There were two (0.3%) relapses, one (0.2%) discontinuation due to side effects and 35 (5.4%) dropouts. SVR rates for patients with active drug use, past drug use and those who never used drugs were 85.4%(n/N = 70/82), 96.1%(n/N = 320/333) and 97.4%(n/N = 223/229) respectively (p < 0.001). After adjustment by sex, age, HCV genotype and opioid agonist therapy, active drug use was the only factor independently associated with SVR (ITT) [adjusted OR (95%confidence interval): 0.29(0.09-0.99),p = 0.048]. CONCLUSIONS: Active drug use was independently associated with lower SVR rates to G/P, mainly due to voluntary dropout. G/P could be particularly beneficial in this scenario but specific strategies designed to increase the retention in care are needed.

Incidence of and factors associated with SARS-CoV-2 infection among people living with HIV in Southern Spain after one year of pandemic.

Whether people living with HIV (PLWH) are at greater risk of acquiring SARS-CoV-2 infection is currently unknown. Prospective serologic studies may allow seroincidence analyses, where all infections are accurately identified. Because of this, we evaluated the incidence of associated factors with and the clinical outcome of SARS-CoV-2 infection in PLWH in Southern Spain. This prospective cohort study included PLWH from a Tertiary University Hospital in Southern Spain. Patients were enrolled in the study if (1) they had attended as outpatients our Unit from 1 August 2019 to 8 February 2020 and (2) had two subsequent evaluations from 9 February 2020 to 4 March 2021. SARS-CoV-2 infections were diagnosed by PCR, antigen detection or serology. Seven hundred and nine PLWH were included in the study. Of them, 55 [7.8%, 95% confidence interval (95% CI) 5.9%-9.9%] patients developed SARS-CoV-2 infection. Between 18 May and 29 November 2020, the rate of seroconversion was 5.3% (95% CI: 3.1%-9.0%) for the general population in the area of Seville and 2.3% (95% CI: 1.3%-2.6%) for PLWH in this study (p = .001). After multivariable analysis, adjusted by age, sex, and risk factors for HIV infection, active tobacco use and CDC stage, active tobacco smoking was the only factor independently associated with lower risk of SARS-Cov-2 infection [Incidence rate ratio: 0.29 (95% CI 0.16-0.55) p < .001]. In conclusion, the incidence of SARS-CoV-2 infection among PLWH in Southern Spain during the ongoing pandemic was lower than that reported for the general population in the same area.

Controlled attenuation parameter-insulin resistance (CIR) score to predict non-alcoholic steatohepatitis.

The diagnosis of non-alcoholic steatohepatitis (NASH) requires liver biopsy. Patients with NASH are at risk of progression to advanced fibrosis and hepatocellular carcinoma. A reliable non-invasive tool for the detection of NASH is needed. We aimed at developing a tool to diagnose NASH based on a predictive model including routine clinical and transient hepatic elastography (TE) data. All subjects undergoing elective cholecystectomy in our center were invited to participate, if alcohol intake was < 30 g/d for men and < 15 g/d for women. TE with controlled attenuation parameter (CAP) was obtained before surgery. A liver biopsy was taken during surgery. Multivariate logistic regression models to predict NASH were constructed with the first 100 patients, the elaboration group, and the results were validated in the next pre-planned 50 patients. Overall, 155 patients underwent liver biopsy. In the elaboration group, independent predictors of NASH were CAP value [adjusted OR (AOR) 1.024, 95% confidence interval (95% CI) 1.002-1.046, p = 0.030] and HOMA value (AOR 1.847, 95% CI 1.203-2.835, p < 0.001). An index derived from the logistic regression equation to identify NASH was designated as the CAP-insulin resistance (CIR) score. The area under the receiver operating characteristic curve (95%CI) of the CIR score was 0.93 (0.87-0.99). Positive (PPV) and negative predictive values (NPV) of the CIR score were 82% and 91%, respectively. In the validation set, PPV was 83% and NPV was 88%. In conclusion, the CIR score, a simple index based on CAP and HOMA, can reliably identify patients with and without NASH.

Severe immunosuppression is related to poorer immunogenicity to SARS-CoV-2 vaccines among people living with HIV.

OBJECTIVES: The aim of this study was to assess the immunogenicity of SARS-CoV-2 available vaccines among people living with HIV (PLWH) after a complete vaccination scheme, and determine predictors of seroconversion. METHODS: This multicentre prospective cohort study included 420 PLWH who had received a standard immunization, either with mRNA or adenoviral-vectored COVID-19 vaccines. Antibody response was evaluated within 1 to 2 months after the last dose of the vaccine with a quantitative determination of antitrimeric spike protein-specific IgG antibodies and IgG neutralizing antibodies. RESULTS: Overall, 384 of 420 PLWH (91%) showed antibody response to vaccination. Seroconversion was observed in 308 of 326 individuals with cluster of differentiation 4 (CD4) counts ≥350 cells/mm3 (95%), 55 of 61 PLWH with 200 to 349 cells/mm3 (90%), and 21 of 33 PLWH with CD4 counts <200 cells/mm3 (64%; p < 0.001). The median log10 IgG neutralization levels were 2.4 IU/mL (Q1-Q3, 1.0-3.1) among PLWH with CD4 counts <200 cells/mm3, 3.1 IU/mL (Q1-Q3, 2.8-3.4) for the 200 to 349 cells/mm3 group, and 3.1 IU/mL (Q1-Q3, 2.7-3.4) for PLWH with CD4 counts ≥350 cells/mm3 (p = 0.016). In the multivariate analysis, CD4 counts ≥350 cells/mm3 (OR: 7.10; 95% CI, 1.91-26.46; p = 0.004) and receiving mRNA-vectored COVID-19 vaccines (OR: 8.19; 95% CI, 3.24-20.70; p ≤ 0.001) were independently associated with a higher probability of response to vaccination. DISCUSSION: HIV-related immunosuppression impairs the antibody response to SARS-CoV-2 vaccines. Specific vaccination schemes should be urgently tailored in this setting, particularly in patients with CD4 cell counts <200 cells/µL. Adenoviral-vectored vaccines should be avoided in PLWH whenever possible.

A Genome-Wide Association Study on Liver Stiffness Changes during Hepatitis C Virus Infection Cure.

Liver stiffness (LS) at sustained virological response (SVR) after direct-acting antivirals (DAA)-based therapy is a predictor of liver events in hepatitis C virus (HCV)-infected patients. The study aim was to identify genetic factors associated with LS changes from the moment of starting anti-HCV therapy to SVR. This prospective study included HCV-infected patients from the GEHEP-011 cohort who achieved SVR with DAA-based therapy, with LS pre-treatment ≥ 9.5 kPa and LS measurement available at SVR. Plink and Magma software were used to carry out genome-wide single-nucleotide polymorphism (SNP)-based and gene-based association analyses, respectively. The ShinyGO application was used for exploring enrichment in Gene Ontology (GO) categories for biological processes. Overall, 242 patients were included. Median (quartile 1, quartile 3) LS values at pre-treatment and at SVR were 16.8 (12, 28) kPa and 12.0 (8.5, 19.3) kPa, respectively. Thirty-five SNPs and three genes reached suggestive association with LS changes from the moment of starting anti-HCV therapy to SVR. GO categories related to DNA packaging complex, DNA conformation change, chromosome organization and chromatin organization were significantly enriched. Our study reports possible genetic factors associated with LS changes during HCV-infection cure. In addition, our results suggest that processes related to DNA conformation are also involved in these changes.