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1.
Clin Infect Dis ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38959300

ABSTRACT

BACKGROUND: Non-AIDS defining malignancies present a growing challenge for persons with HIV (PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish IMPAC-Neo protocol was designed to compare two comprehensive cancer screening strategies integrated into routine HIV care. This study reports baseline data on the prevalence and types of precancerous lesions and early-stage cancer among participants at enrolment. Acceptability of the procedure was additionally assessed. METHODS: Cross-sectional analysis of a comprehensive screening protocol to detect precancer and cancer. The readiness of healthcare providers to implement the protocol was evaluated using a validated 4-item survey. RESULTS: Among the 1430 enrolled PWH, 1172 underwent 3181 screening tests, with positive findings in 29.4% of cases, leading to further investigation in 20.7%. Adherence to the protocol was 84%, with HIV providers expressing high acceptability (97.1%), appropriateness (91.4%), and feasibility (77.1%). A total of 145 lesions were identified in 109 participants, including 60 precancerous lesions in 35 patients (3.0%), 9 early-stage cancers in 9 patients (0.8%), and 76 low-risk lesions in 65 subjects (5.5%). Adverse events related to screening occurred in 0.8% of participants, all mild. The overall prevalence of cancer precursors or early-stage cancer was 3.8% (95% CI, 2.74%-5.01%), with highest rates observed in individuals screened for anal and colorectal cancers. CONCLUSIONS: The baseline comprehensive cancer screening protocol of the IMPAC-Neo study successfully identified a significant proportion of PWH with precancerous lesions and early-stage cancer. High adherence rates and positive feedback from providers suggest effective implementation potential in real-world healthcare settings.

2.
One Health ; 18: 100690, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39010960

ABSTRACT

Paslahepevirus balayani (formerly known as hepatitis E virus) is an emerging cause of foodborne disease in Europe, transmitted mainly by the consumption of raw or undercooked pork. Since little is known about the presence of the virus in several pork products that are eaten uncooked, our aim was to evaluate the prevalence of Paslahepevirus balayani in groups of commercial pork products intended for human consumption subjected to different processing techniques. A total of 1265 samples of pork products from Spain were divided into four groups and tested for the presence of Paslahepevirus balayani RNA: unprocessed pig and wild boar meat frozen at -20 °C (n = 389), dry-cured pork products (n = 391), dry-cured and salted pork products (n = 219), and boiled products (n = 266) (none of these products contained pork liver). Five samples were positive for Paslahepevirus balayani RNA (overall prevalence: 0.4%; 95% CI: 0.17% - 0.92%). All positive samples were from unprocessed meat stored at -20 °C, with a prevalence in this group of 1.3% (95% CI: 0.42-3.44); two samples came from pigs (1.1%; 95% CI: 0.13-3.81) and three from wild boar (1.5%; 95% CI: 0.31-4.28). None of the pork samples in the other groups was positive. In conclusion, Paslahepevirus balayani was found in unprocessed swine products form Spain, but not in processed products intended to be consumed undercooked, demonstrating that transmission of this zoonotic virus by eating these pork products should be more seriously considered.

3.
Emerg Infect Dis ; 30(7): 1496-1498, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38916587

ABSTRACT

We analyzed West Nile Virus (WNV) exposure from 1,222 blood donors during 2017-2018 from an area of south-central Spain. Results revealed WNV seroprevalence of 0.08% (95% CI 0.004%-0.4%) in this population. Our findings underscore the need for continued surveillance and research to manage WNV infection in this region.


Subject(s)
Antibodies, Viral , Blood Donors , West Nile Fever , West Nile virus , Humans , Spain/epidemiology , West Nile Fever/epidemiology , West Nile virus/immunology , Seroepidemiologic Studies , Male , Female , Adult , Middle Aged , Antibodies, Viral/blood , Young Adult , Adolescent , Aged
4.
J Pediatr ; 273: 114125, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815747

ABSTRACT

Two of 11 children with acute hepatitis of unknown origin were found to have rat hepatitis E virus infection. This infection should be considered in the differential diagnosis of children with acute hepatitis of unknown origin.

5.
Open Forum Infect Dis ; 11(4): ofae112, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38560607

ABSTRACT

Objective: The incidence of type 2 diabetes mellitus (T2DM) has risen dramatically. Among people living with HIV (PLHIV), chronic disease (now >15 cases/1000 in the general population worldwide) and long-term exposure to antiretroviral therapy (ART) can alter metabolic processes early, favoring insulin resistance and T2DM. We retrospectively studied the incidence of T2DM and associated factors in the Cohort of the Spanish AIDS Research Network, a prospective cohort of PLHIV enrolled at diagnosis and before initiation of ART. Methods: PLHIV were aged >18 years and ART naive at inclusion. The incidence of new diagnoses of T2DM after initiation of ART (per 1000 person-years) was calculated. Predictors of a diagnosis of T2DM were identified by a Cox proportional hazards model adjusted for statistically significant and clinically relevant variables. Results: Cumulative incidence was 5.9 (95% CI, 5.1-6.7) per 1000 person-years, increasing significantly in persons aged >50 years to 14.4 (95% CI, 10.4-19.3). Median time to diagnosis of T2DM was 27 months. Only age and higher education were significant. Interestingly, higher education was associated with a 33% reduction in the incidence of T2DM. Having received tenofovir disoproxil fumarate + (lamivudine or emtricitabine) + rilpivirine was almost significant as a protective factor (hazard ratio, 0.49; 95% CI, .24-1.01; P = .05). Conclusions: The incidence of T2DM in PLHIV in Spain was high, especially in persons aged >50 years. Age was the factor most closely associated with onset, and educational level was the factor most associated with reduced risk. We highlight the lack of association between HIV-related factors and T2DM and show that, within nonnucleoside reverse transcriptase inhibitors, rilpivirine could prove more benign for metabolic comorbidities.

6.
Emerg Infect Dis ; 30(4): 823-826, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38526410

ABSTRACT

We identified rat hepatitis E virus (HEV) RNA in farmed pigs from Spain. Our results indicate that pigs might be susceptible to rat HEV and could serve as viral intermediaries between rodents and humans. Europe should evaluate the prevalence of rat HEV in farmed pigs to assess the risk to public health.


Subject(s)
Hepatitis E virus , Humans , Rats , Animals , Swine , Spain/epidemiology , Hepatitis E virus/genetics , Europe , Farms , Public Health , RNA
7.
J Clin Invest ; 134(8)2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38376918

ABSTRACT

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation.


Subject(s)
HIV Infections , HIV-1 , Humans , HIV-1/genetics , Leukocytes, Mononuclear , Proviruses/genetics , HIV Infections/drug therapy , Anti-Retroviral Agents/therapeutic use
8.
Antiviral Res ; 222: 105795, 2024 02.
Article in English | MEDLINE | ID: mdl-38181855

ABSTRACT

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.


Subject(s)
Hepacivirus , Hepatitis C , Humans , Hepacivirus/genetics , Case-Control Studies , Retrospective Studies , Genome-Wide Association Study , Seroconversion , Genotype , Receptors, KIR/genetics
9.
Emerg Microbes Infect ; 13(1): 2295389, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38095070

ABSTRACT

Rat hepatitis E virus (ratHEV; species Rocahepevirus ratti) is considered a newly emerging cause of acute hepatitis of zoonotic origin. ratHEV infection of people living with HIV (PLWH) might portend a worse, as with hepatitis E virus (HEV; species Paslahepevirus balayani), and consequently this group may constitute a high-risk population. We aimed to evaluate the prevalence of ratHEV by measuring viral RNA and specific IgG antibodies in a large Spanish cohort of PLWH. Multicentre study conducted in Spain evaluating PLWHIV included in the Spanish AIDS Research Network (CoRIS). Patients were evaluated for ratHEV infection using PCR at baseline and anti-ratHEV IgG by dot blot analysis to evaluate exposure to ratHEV strains. Patients with detectable ratHEV RNA were followed-up to evaluate persistence of viremia and IgG seroconversion. Eight-hundred and forty-two individuals were tested. A total of 9 individuals showed specific IgG antibodies against ratHEV, supposing a prevalence of 1.1 (95% CI; 0.5%-2.1%). Of these, only one was reactive to HEV IgG antibodies by ELISA. One sample was positive for ratHEV RNA (prevalence of infection: 0.1%; 95% CI: 0.08%-0.7%). The case was a man who had sex with men exhibiting a slightly increased alanine transaminase level (49 IU/L) as only biochemical alteration. In the follow-up, the patients showed undetectable ratHEV RNA and seroconversion to specific ratHEV IgG antibodies. Our study shows that ratHEV is geographical broadly distributed in Spain, representing a potential zoonotic threat.


Subject(s)
HIV Infections , Hepatitis E virus , Hepatitis E , Male , Humans , Animals , Rats , Hepatitis E virus/genetics , Hepatitis E/epidemiology , Hepatitis Antibodies , RNA, Viral , Immunoglobulin G , HIV Infections/complications
10.
AIDS ; 38(3): 387-395, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37905999

ABSTRACT

OBJECTIVE: To estimate life expectancy of people with HIV (PWH) and describe causes of death. DESIGN: Antiretroviral therapy (ART)-naive adults from the CoRIS cohort starting ART in 2004-2019. METHODS: We calculated life expectancy at age 40 for men and women according to their ART initiation period, and stratified by transmission category, CD4 + cell count and AIDS diagnosis. We estimated life expectancy in 10-year age bands using life tables constructed from mortality rates, estimated through Poisson models. RESULTS: Life expectancy increased from 65.8 [95% confidence interval (CI) 65.0-66.6] in 2004-2008 to 72.9 (72.2-73.7) in 2014-2019 in men [general population comparators (GPC): 79.1 and 81.2 years, respectively] and from 65.8 (65.0-66.6) to 72.5 (71.8-73.3) in women (GPC: 84.9 and 86.4, respectively). Non-AIDS-related deaths accounted for 68% of deaths among men and 78% among women. Life expectancy was longer when starting ART with higher CD4 + cell counts and without AIDS. For men acquiring HIV through sex with men, starting ART in 2014-2019 without AIDS, life expectancy was 75.0 (74.2-75.7) with CD4 + cell count less than 200 cells/µl, rising to 78.1 (77.5-78.8) with CD4 + cell count at least 350 cells/µl. Corresponding figures were 70.1 (69.4-70.9) and 76.0 (75.3-76.7) for men acquiring HIV heterosexually (HTX) and 61.5 (60.7-62.3) and 69.0 (68.2-69.8) for those acquiring HIV through injection drug use (IDU). For women starting ART from 2014 without AIDS, life expectancy increased from 71.7 (71.0-72.4) to 77.3 (76.7-77.9) among HTX and from 63.7 (62.9-64.5) to 70.7 (70.0-71.5) among IDU. CONCLUSION: Our findings confirm the progressive improvement of life expectancy in PWH in Spain over the last decades, supporting the insurability of PWH on suppressive ART in our current setting and time.


Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Adult , Male , Humans , Female , HIV Infections/epidemiology , Spain/epidemiology , Cohort Studies , Life Expectancy , CD4 Lymphocyte Count
11.
Int J Antimicrob Agents ; 63(1): 107016, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37890734

ABSTRACT

OBJECTIVES: The efficacy of BIC/FTC/TAF in HIV late presenters initiating antiretroviral therapy (ART) has not been sufficiently evaluated. METHODS: The aim of this study was to assess the effectiveness and tolerability of BIC/FTC/TAF compared to other first-line antiretroviral regimens in treatment-naïve adult individuals from the CoRIS Cohort starting ART with CD4 counts <200 cells/mm3 and/or AIDS-defining conditions between January 1st 2019 and November 30th 2020. Logistic regression models were used to estimate odds ratios (ORs) of association between initial regimen and achievement of viral suppression (VS) (primary objective), defined as HIV RNA <50 cop/mL, and immunological recovery (IR) (secondary objective), defined as CD4 count >200 cells/mm3, at weeks 24 and 48 after initiation of ART. RESULTS: We evaluated 314 individuals (84.7% men, median age 40 years). Of them, 158 initiated with BIC/FTC/TAF. At inclusion, 117 had an AIDS-defining condition. In multivariable analyses, individuals with AIDS-defining conditions initiating ART with BIC/FTC/TAF achieved higher rates of VS at 24 weeks than other regimens (aOR: 0.2; 95% CI: 0.06-0.64) and, at 48 weeks, than DTG/ABC/3TC (aOR: 0.06; 95% CI: 0.01-0.76) and DTG + TDF/3TC (aOR: 0.2; 95% CI: 0.47-0.9). No other differences in VS or IR were observed. At 24 and 48 weeks after ART initiation, treatment discontinuations were lower with BIC/FTC/TAF than with other regimens (3.2% and 7.6% vs. 24.4% and 37.8%, respectively; P < 0.005). CONCLUSION: Our results suggest that BIC/FTC/TAF could be a preferred regimen as initial therapy in HIV late presenters because of its high effectiveness and good tolerability.


Subject(s)
Acquired Immunodeficiency Syndrome , Alanine , Amides , Anti-HIV Agents , HIV Infections , Heterocyclic Compounds, 3-Ring , Piperazines , Pyridones , Tenofovir/analogs & derivatives , Adult , Male , Humans , Female , Anti-HIV Agents/adverse effects , Acquired Immunodeficiency Syndrome/drug therapy , HIV Infections/drug therapy , Drug Combinations , Emtricitabine/adverse effects
12.
One Health ; 17: 100619, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38024277

ABSTRACT

Paslahepevirus balayani (HEV) is an important emerging zoonotic virus in Europe. Although domestic pigs and wild boar are the main reservoirs of this pathogen, susceptibility to this virus has been confirmed in a growing number of animal species, including equines. However, their role in the epidemiology of this virus remains poorly understood. Our aim was to assess HEV circulation and identify potential risk factors associated with exposure in equid species in different European countries. A total of 596 equines, including 496 horses, 63 donkeys and 37 mules/hinnies bred in four European countries (Spain, Italy, United Kingdom and Ireland) were sampled. Thirty-three animals (5.5%; 95%CI: 3.7-7.4) had anti-HEV antibodies. Seropositivity was found in 4.6% of horses, 11.1% of donkeys and 8.1% of mules/hinnies tested. By country, 6.3%, 5.4%, 5.0% and 4.0% of the equines sampled in Spain, Italy, United Kingdom and Ireland, respectively, were seropositive, respectively. Statistical analysis showed that "species" and "drinking water from ponds and streams" were potential risk factors associated with HEV seropositivity in equines in Europe. HEV RNA was not detected in any (0.0%; 95%CI: 0.0-1.8) of the 202 equines tested. Our results provide evidence of a low, spatially homogeneous and widespread viral circulation that is not equal across species in equid populations in the European countries analyzed and indicate that these species appear to play a limited role in the epidemiology of this virus. Further studies are required to elucidate the differences in seroprevalence between donkeys, mules/hinnies and horses and to determine the risk of zoonotic transmission of this pathogen from equid species.

13.
Front Microbiol ; 14: 1247467, 2023.
Article in English | MEDLINE | ID: mdl-37822752

ABSTRACT

Introduction: Paslahepevirus balayani (Hepatitis E virus; HEV) is an emerging virus that poses as a public health threat. The virus is now reported to be the leading cause of acute viral hepatitis, with a unique impact on African settings. Our aim was to evaluate the prevalence and risk factors for HEV infection in three cohorts (animal handlers, villagers, and students). Methods: A prospective cross-sectional study was carried out on a total of 752 subjects from southwestern Nigeria. In all individuals, anti-HEV IgG and anti-HEV IgM antibodies were evaluated by using ELISA (confirming positive results via immunoblotting), and serum viral RNA was evaluated by using two RT-PCR assays. Results: The overall seroprevalence of HEV IgG and HEV IgM was 14.9% (95% CI: 12.5-17.6%) and 1.3% (95% CI: 0.7-2.5%), respectively. We observed the highest seroprevalence among animal contact individuals, with butchers being the population with the highest HEV IgG seroprevalence (31.1%). Similarly, HEV IgM was higher in the animal contact group (2.2%) than in the non-animal contact cohort (0%). Discussions: Viral RNA was not detected in any of the samples. Butchering was significantly associated with higher HEV prevalence. Although all efforts to prevent HEV in Africa have focused on the chlorination of water, our study suggests that most new infections could currently be linked to animal manipulation. Therefore, education and guidelines must be provided in southwest Nigeria to ensure that animal handling and processing methods are safe.

14.
Front Endocrinol (Lausanne) ; 14: 1230046, 2023.
Article in English | MEDLINE | ID: mdl-37810880

ABSTRACT

Background & objective: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in people living with HIV (PLWH) and the expression of some microRNAs could be useful as biomarkers for the diagnosis of NAFLD. The aim of this study was to identify patterns of differential expression of microRNAs in PLWH and assess their diagnostic value for NALFD. Methods: A discovery case-control study with PLWH was carried out. The expression of miRNAs was determined using HTG EdgeSeq technology. Cases were defined as patients with severe NAFLD and controls as patients without NAFLD, characterized using the controlled attenuation parameter (CAP). Cases and controls were matched 1:1 for age, sex, BMI, CD4+ lymphocyte count, active HCV infection, and ART regimen. Results: Serum 2,083 simultaneous microRNA transcripts were analyzed using HTG technology and compared between cases and controls. Forty-five patients, 23 cases, and 22 controls were included in the study. In the analysis of the expression pattern of the 2,083 microRNAs, no differential expression patterns were found between both groups of patients included in the study. Conclusion: Analysis of the microRNA transcriptome profile of nonobese PLWH with severe NAFLD did not appear to differ from that of patients without NAFLD. Thus, microRNA might not serve as a proper biomarker for predicting severe NALFD in this population.


Subject(s)
HIV Infections , MicroRNAs , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/diagnosis , MicroRNAs/genetics , HIV , Case-Control Studies , HIV Infections/complications , HIV Infections/genetics , Biomarkers
15.
J Antimicrob Chemother ; 78(10): 2591-2596, 2023 10 03.
Article in English | MEDLINE | ID: mdl-37671831

ABSTRACT

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.


Subject(s)
Coinfection , HIV Infections , Hepatitis C, Chronic , Humans , Antiviral Agents/pharmacology , Coinfection/drug therapy , Coinfection/complications , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , HIV Infections/complications , HIV Infections/drug therapy , Clinical Trials as Topic , Multicenter Studies as Topic
16.
J Antimicrob Chemother ; 78(11): 2696-2701, 2023 11 06.
Article in English | MEDLINE | ID: mdl-37725999

ABSTRACT

OBJECTIVES: To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in heavily treatment-experienced people living with HIV (PLWH). METHODS: Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)< 50 copies/mL at Week 48 (ITT). RESULTS: We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5-734.5), 24 years on ART (IQR: 15.9-27.8). The median number of pills was 4 (range: 3-10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VL < 50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters. CONCLUSIONS: Our data suggest that BIC/FTC/TAF + darunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.


Subject(s)
Anti-HIV Agents , HIV Infections , Adult , Female , Humans , Male , Adenine/therapeutic use , Alanine/therapeutic use , Anti-HIV Agents/adverse effects , Anti-Retroviral Agents/therapeutic use , Cobicistat/therapeutic use , Darunavir/therapeutic use , DNA/therapeutic use , Emtricitabine/therapeutic use , HIV Infections/drug therapy , Prospective Studies , Tandem Mass Spectrometry
17.
Front Med (Lausanne) ; 10: 1151843, 2023.
Article in English | MEDLINE | ID: mdl-37484846

ABSTRACT

Introduction: Whole-body autopsies may be crucial to understand coronavirus disease 2019 (COVID-19) pathophysiology. We aimed to analyze pathological findings in a large series of full-body autopsies, with a special focus on superinfections. Methods: This was a prospective multicenter study that included 70 COVID-19 autopsies performed between April 2020 and February 2021. Epidemiological, clinical and pathological information was collected using a standardized case report form. Results: Median (IQR) age was 70 (range 63.75-74.25) years and 76% of cases were males. Most patients (90%,) had at least one comorbidity prior to COVID-19 diagnosis, with vascular risk factors being the most frequent. Infectious complications were developed by 65.71% of the patients during their follow-up. Mechanical ventilation was required in most patients (75.71%) and was mainly invasive. In multivariate analyses, length of hospital stay and invasive mechanical ventilation were significantly associated with infections (p = 0.036 and p = 0.013, respectively). Necropsy findings revealed diffuse alveolar damage in the lungs, left ventricular hypertrophy in the heart, liver steatosis and pre-infection arteriosclerosis in the heart and kidneys. Conclusion: Our study confirms the main necropsy histopathological findings attributed to COVID-19 in a large patient series, while underlining the importance of both comorbid conditions and superinfections in the pathology.

18.
Infect Dis Ther ; 12(8): 2039-2055, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37452174

ABSTRACT

INTRODUCTION: Current antiretroviral therapies (ARTs) have improved outcomes for people living with HIV. However, the requirement to adhere to lifelong daily oral dosing may be challenging for some people living with HIV, leading to suboptimal adherence and therefore reduced treatment effectiveness. Treatment with long-acting (LA) ART may improve adherence and health-related quality of life. The objective of this study was to evaluate the cost-effectiveness of cabotegravir + rilpivirine (CAB+RPV) LA administered every 2 months (Q2M) compared with current ART administered as daily oral single-tablet regimens (STRs) from a Spanish National Healthcare System perspective. METHODS: A hybrid decision-tree and Markov state-transition model was used with pooled data from three phase III/IIIb trials (FLAIR, ATLAS, and ATLAS-2M) over a lifetime horizon, with health states defined by viral load and CD4+ cell count. Direct costs (in €) were taken from Spanish public sources from 2021 and several deterministic and probabilistic analyses were carried out. An annual 3% discount rate was applied to both costs and utilities. RESULTS: Over the lifetime horizon, CAB+RPV LA Q2M was associated with an additional 0.27 quality-adjusted life years (QALYs) and slightly greater lifetime costs (€4003) versus daily oral ART, leading to an incremental cost-effectiveness ratio of €15,003/QALY, below the commonly accepted €30,000/QALY willingness-to-pay threshold in Spain. All scenario analyses showed consistent results, and the probabilistic sensitivity analysis showed cost-effectiveness compared with daily oral STRs in 62.4% of simulations, being dominant in 0.3%. CONCLUSION: From the Spanish National Health System perspective, CAB+RPV LA Q2M is a cost-effective alternative compared with the current options of daily oral STR regimens for HIV treatment. CLINICAL TRIALS REGISTRATION: ATLAS, NCT02951052; ATLAS-2M, NCT03299049; FLAIR, NCT02938520.


Over the past decades, treatments for HIV infection have improved outcomes for people living with HIV. However, most of the treatments available consist of daily oral administration, which may present challenges for some people. These challenges may lead to a less optimal intake of the medicines and, therefore, to a potential reduction of treatment effectiveness. A new long-acting treatment alternative for HIV with two drugs is now available: cabotegravir + rilpivirine long-acting is the first injectable treatment administered in the muscle every 2 months by a healthcare professional. Long-acting injectables may improve treatment administration and health-related quality of life of people living with HIV. This study estimated the cost-effectiveness of cabotegravir + rilpivirine long-acting in Spain compared with daily oral single-tablet treatment for HIV. An economic model using clinical data and Spanish inputs was used to estimate cost-effectiveness and health outcomes over a lifetime. Cabotegravir + rilpivirine long-acting compared with daily oral single-tablet treatment showed an increase in health-related quality of life, leading to a cost-effectiveness ratio of €15,003, below the Spanish willingness-to-pay threshold of €30,000. All different scenarios tested showed consistent results, with cabotegravir + rilpivirine long-acting being cost-effective in 62.4% of the simulations and less costly and more effective in 0.3%. This study demonstrated that, in Spain, cabotegravir + rilpivirine long-acting administered every 2 months is a cost-effective alternative to the current daily oral single-tablet treatment options for HIV.

19.
Nephron ; 147(9): 560-571, 2023.
Article in English | MEDLINE | ID: mdl-37276852

ABSTRACT

INTRODUCTION: Inflammation is a risk factor for diabetes in the general population. The role of inflammation in prediabetes or post-transplant diabetes mellitus (PTDM) is not clear. We evaluated the association between inflammatory markers in patients on the waiting list for renal transplantation and the onset of prediabetes and PTDM 12 months after transplantation. METHODS: This is a post hoc analysis of a prospective study that included nondiabetic patients on the waiting list for kidney transplantation who underwent an oral glucose tolerance test (OGTT) and were followed up to 12 months after transplantation. At this time, those patients without PTDM underwent another OGTT. At pre-transplantation, five cytokines: TNFα, IL6, IL1ß, CRP, MCP1 were determined. The association between inflammation and prediabetes/PTDM was evaluated using multiple regression models. RESULTS: 110 patients on the waiting list were enrolled: 74 had normal glucose metabolism and 36 had prediabetes or occult diabetes. At 12 months, 53 patients had normal glucose metabolism, 25 prediabetes, and 32 PTDM. In multiple regression analysis, pre-transplant inflammation was not a risk factor for prediabetes or PTDM. This was attributed to the high interrelation between obesity, prediabetes, and inflammation: about 75% of the cases had these conditions. In a sub-analysis, we analyzed only patients without prediabetes and occult diabetes on the waiting list and found that TNFα levels and BMI at pre-transplantation were independently associated with the onset of prediabetes or PTDM 1 year after transplantation. CONCLUSIONS: Pre-transplant inflammation and BMI are risk factors for prediabetes and PTDM in patients without glucose metabolism alterations.


Subject(s)
Diabetes Mellitus , Prediabetic State , Humans , Prediabetic State/etiology , Prospective Studies , Tumor Necrosis Factor-alpha , Waiting Lists , Blood Glucose/analysis , Diabetes Mellitus/epidemiology , Diabetes Mellitus/etiology , Risk Factors , Inflammation/complications , Postoperative Complications
20.
One Health ; 16: 100539, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37363253

ABSTRACT

Introduction: Paslahepevirus balayani (HEV) is an endemic zoonotic disease ranked as a major cause of acute hepatitis in Europe. Most infections occurring in Europe are due to the endemic several subtypes of genotype 3, through the consumption of raw or undercooked pork, observing a genotype geographical distribution pattern among countries Because of global changes in the pig and pork trading markets, subtype distribution might vary. We aimed to evaluate the temporal distribution of HEV genotypes in patients from southern Spain with acute hepatitis to determine whether these changes were related to the pig import trade during the study period between 2018 and 2022. Methods: Prospective longitudinal study including patients with acute hepatitis from southern Spain between 2018 and 2022. HEV RNA and antibodies was tested in all patients. In patients with detectable HEV RNA, genotype was obtained. To determine the number of imported pigs and their origins, we checked the official data from the Spanish statistics on international trade of Spanish Minister of Industry during by country of origin during the same study period. Results: A total of 659 patients with acute hepatitis were included in the study. Among them, 162 (24.5%) had at least one marker (IgM or RNA) of acute HEV infection. Among the 71 patients with detectable viral RNA, genotypes could be obtained for 58 (81.6%). The most prevalent HEV genotype was 3f (n = 48; 78.6%), showing a decreasing prevalence of over time, from 100% in 2018 to 70.6% in 2022. Since 2021, the emergence of other genotypes has been determined. A significant increase in the number of animals imported was observed since the beginning of the study. Denmark experienced a significant rise, from 0.03% in 2018 of total imports to 10.4% in 2022. Conclusions: HEV molecular diversity is changing in Spain, could be linked to changes in fattening pig import origin.

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