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People living with HIV are particularly susceptible to developing metabolic disorders, including metabolic dysfunction-associated steatotic liver disease and other forms of SLD. However, people living with HIV have been historically excluded from clinical trials and large cohort studies of SLD. Therefore, our understanding of the risk factors and natural history of SLD in this population is poor. Moreover, relevant knowledge gaps on the epidemiology and barriers for adequate health care, such as stigma, hamper adequate responses to the ongoing HIV and SLD syndemic. This Viewpoint provides a comprehensive perspective on how to tackle SLD in people living with HIV by examining the role of social determinants of health in the development of liver disease and metabolic syndrome comorbidities among this population, emphasising the importance of prioritising SLD management, summarising the most urgent needs in the field, and offering recommendations for advancing research to fill key data gaps and protect liver health of people living with HIV.
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Infecciones por VIH , Humanos , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Factores de Riesgo , Hígado Graso/epidemiología , Determinantes Sociales de la Salud , Comorbilidad , Estigma Social , Síndrome Metabólico/epidemiologíaRESUMEN
Background: Effective antiretroviral therapy (ART) has substantially reduced acquired immunodeficiency syndrome (AIDS)-related deaths, shifting the focus to non-AIDS conditions in people living with human immunodeficiency virus (HIV) (PLWH). We examined mortality trends and predictors of AIDS- and non-AIDS mortality in the Population HIV Cohort from Catalonia and Balearic Islands (PISCIS) cohort of PLWH from 1998 to 2020. Methods: We used a modified Coding Causes of Death in HIV protocol, which has been widely adopted by various HIV cohorts to classify mortality causes. We applied standardized mortality rates (SMR) to compare with the general population and used competing risks models to determine AIDS-related and non-AIDS-related mortality predictors. Results: Among 30 394 PLWH (81.5% male, median age at death 47.3), crude mortality was 14.2 per 1000 person-years. All-cause standardized mortality rates dropped from 9.6 (95% confidence interval [CI], 8.45-10.90) in 1998 through 2003 to 3.33 (95% CI, 3.14-3.53) in 2015 through 2020, P for trend = .0001. Major causes were AIDS, non-AIDS cancers, cardiovascular disease, AIDS-defining cancers, viral hepatitis, and nonhepatitis liver disease. Predictors for AIDS-related mortality included being aged ≥40 years, not being a man who have sex with men, history of AIDS-defining illnesses, CD4 < 200 cells/µL, ≥2 comorbidities, and nonreceipt of ART. Non-AIDS mortality increased with age, injection drug use, heterosexual men, socioeconomic deprivation, CD4 200 to 349 cells/µL, nonreceipt of ART, and comorbidities, but migrants had lower risk (adjusted hazard risk, 0.69 [95% CI, .57-.83]). Conclusions: Mortality rates among PLWH have significantly decreased over the past 2 decades, with a notable shift toward non-AIDS-related causes. Continuous monitoring and effective management of these non-AIDS conditions are essential to enhance overall health outcomes.
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BACKGROUND: Capsaicin is a highly selective agonist of the transient receptor potential vanilloid 1. The adhesive capsaicin patch provides a high capsaicin concentration (8%) directly in the painful area - its efficacy in benign peripheral neuropathic pain (diabetic neuropathy or postherpetic neuralgia) has recently been described in the literature. However, there is scant evidence of its efficacy in chemotherapy-induced peripheral neuropathy (CIPN). This is a concern for patients with multiple myeloma, who suffer from peripheral neuropathic pain induced by first-line treatments (bortezomib or thalidomide). AIM: To describe improved control of CIPN in patients with multiple myeloma using adhesive capsaicin 8% patch. METHODS: We opted for a retrospective observational case series. Between October 2017 and October 2020, we collected clinical data from adult multiple myeloma patients affected by CIPN who were administered the capsaicin 8% patch in our palliative care outpatient clinic. We compiled Numerical Pain Rating Scale (NPRS) scores, patients' medication needs and performance status before and after patch application. RESULTS: Two women and five men with an average age of 62.85 years received bortezomib. Two patients (28.57% of the sample) also received thalidomide. The average NPRS score before patch application was 6.42/10. Five of the seven patients (71.42%) received a mean daily oral morphine dose of 52.85â mg/day, five (71.42%) received gabapentinoids and one (14.28%) received antidepressants. The average NPRS score decreased to 4/10 seven days after patch application, while the mean daily oral morphine dose remained stable. Performance status improved slightly in two patients (28.57%) and remained stable in the rest. One patient (14.28%) required an extra analgesic dose during patch application. CONCLUSIONS: Capsaicin 8% patch application appears to reduce pain intensity in patients with multiple myeloma suffering from CIPN.
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Bortezomib , Capsaicina , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Capsaicina/administración & dosificación , Anciano , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Bortezomib/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Parche Transdérmico , Talidomida/administración & dosificación , Talidomida/efectos adversos , Talidomida/uso terapéutico , Dimensión del Dolor , Neuralgia/tratamiento farmacológico , Neuralgia/inducido químicamenteRESUMEN
PURPOSE: This study aimed to compare trichloroacetic acid (TCA) versus electrocautery (ECA) for the treatment of anal high-grade squamous intraepithelial lesions (HSIL). METHODS: This is an observational, single-center study. All subjects with HIV who had anal HSIL treated with TCA or ECA from 2010 to 2022 were included. Effectiveness was evaluated by on-treatment analysis, defining response as the resolution of HSIL and recurrence as a new diagnosis of HSILs during follow-up. A propensity score analysis was used to adjust for confounding factors. RESULTS: In total, 227 and 260 HSIL episodes were treated with ECA and TCA, respectively. Response was observed in 61.7% (95% CI: 55.3-68) of cases treated with ECA and in 73.1% (95% CI: 67.8-78.5) with TCA (p = .004). The effectiveness of TCA was higher in large and multifocal HSILs. Side effects were common with both treatments, but no serious events were described. Tolerability was good in 77.1% and 80.7% of patients treated with ECA and TCA, respectively. At 24 months, recurrent HSIL were observed in 36.3% (95% CI: 27.3-45) and 28% (95% CI: 20.2-35.8) in the ECA and TCA groups (p = .049). A nadir CD4 cell count ≤200 cells/µl was found to be a risk factor for recurrence (OR: 1.77; 95% CI: 1.12-2.78). CONCLUSIONS: In this study, treatment with TCA showed high effectiveness, low recurrence and good tolerability. Considering the benefits of TCA, it could be considered one of the first-line treatments for anal HSIL.
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Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Humanos , Masculino , Ácido Tricloroacético/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Resultado del Tratamiento , Neoplasias del Ano/tratamiento farmacológico , Neoplasias del Ano/patología , Electrocoagulación , Homosexualidad MasculinaRESUMEN
Human immunodeficiency virus (HIV) infection induces immunological dysfunction, which limits the elimination of HIV-infected cells during treated infection. Identifying and targeting dysfunctional immune cells might help accelerate the purging of the persistent viral reservoir. Here, we show that chronic HIV infection increases natural killer (NK) cell populations expressing the negative immune regulator KLRG1, both in peripheral blood and lymph nodes. Antiretroviral treatment (ART) does not reestablish these functionally impaired NK populations, and the expression of KLRG1 correlates with active HIV transcription. Targeting KLRG1 with specific antibodies significantly restores the capacity of NK cells to kill HIV-infected cells, reactivates latent HIV present in CD4+ T cells co-expressing KLRG1, and reduces the intact HIV genomes in samples from ART-treated individuals. Our data support the potential use of immunotherapy against the KLRG1 receptor to impact the viral reservoir during HIV persistence.
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Infecciones por VIH , VIH-1 , Receptores Inmunológicos , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Células Asesinas Naturales , Lectinas Tipo C/genética , Receptores Inmunológicos/genética , Latencia del VirusRESUMEN
OBJECTIVES: We aimed to determine if starting antiretroviral therapy (ART) in the first 30 days after acquiring HIV infection has an impact on immunovirological response. METHODS: Observational, ambispective study including 147 patients with confirmed acute HIV infection (January/1995-August/2022). ART was defined as very early (≤30 days after the estimated date of infection), early (31-180 days), and late (>180 days). We compared time to viral suppression (viral load [VL] <50 copies/ml) and immune recovery (IR) (CD4+/CD8+ ratio ≥1) according to the timing and type of ART using survival analysis. RESULTS: ART was started in 140 (95.2%) patients. ART was very early in 24 (17.1%), early in 77 (55.0%), and late in 39 (27.9%) cases. Integrase strand transfer inhibitor (INSTI)-based regimens were the most used in both the overall population (65%) and the very early ART group (23/24, 95.8%). Median HIV VL and CD4+/CD8+ ratio pre-ART were higher in the very early ART group (P <0.05). Patients in the very early and early ART groups and treated with INSTI-based regimens achieved IR earlier (P <0.05). Factors associated with faster IR were the CD4+/CD8+ ratio pre-ART (hazard ratio: 9.3, 95% CI: 3.1-27.8, P <0.001) and INSTI-based regimens (hazard ratio: 2.4, 95% CI: 1.3-4.2, P = 0.003). CONCLUSIONS: The strongest predictors of IR in patients who start ART during AHI are the CD4+/CD8+ ratio pre-ART and INSTI-based ART regimens.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Carga ViralRESUMEN
Introduction: Second-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients. Methods: Real-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated. Results: Virological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/µL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles. Discussion: Whereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available.
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Cobicistat , Infecciones por VIH , Adulto , Humanos , España , Estudios Prospectivos , Integrasas , Infecciones por VIH/tratamiento farmacológicoRESUMEN
BACKGROUND: People living with HIV (PLWH) face structural and psychosocial factors that affect health-related quality of life (HRQoL). We aimed to evaluate how syndemic conditions affected HRQoL in PLWH. METHODS: A cross-sectional survey was conducted among 861 PLWH, to determine whether syndemic conditions (monthly income; sexual satisfaction; depressive symptoms; social role satisfaction; social isolation; cognitive function; nicotine dependence; perception of stigma) have an effect on HRQoL. A linear regression model and measures of Additive Interaction (AI) were used to determine the effects of syndemic conditions on HRQoL, controlling for other risk factors. RESULTS: Overall, the most frequently observed were stigma perception (56.9%), poor cognitive function (50.6%) and the perception of social isolation (51.6%). The presence of depressive symptoms was the risk factor most associated with worse Physical Health (PH) (B 3.93, 2.71-5.15) and Mental Health (MH) (B 5.08, 3.81-6.34) in linear regression model. Specifically, an interaction was observed between poor cognitive function and poor satisfaction with social role on worse PH and MH (AI 2.08, 0.14-4.02; AI 2.69, 0.15-5.22, respectively); and low income and perception of stigma (AI 2.98, 0.26-5.71), low income and perception of social isolation (AI 2.79, 0.27-5.32), and low income and poor satisfaction with social role (AI 3.45, 0.99-5.91) on MH. CONCLUSION: These findings provide evidence that syndemic factors impact HRQoL. HIV prevention programs should screen and address co-occurring health problems to improve patient-centered health care and outcomes.
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Infecciones por VIH , Calidad de Vida , Humanos , Estudios Transversales , Calidad de Vida/psicología , España/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Sindémico , Estigma SocialRESUMEN
An aneurysmal bone cyst (ABC) is a rare bone tumor usually observed in long bones. The surgical treatment of this pathology is often related to high recurrence rates, so novel biological techniques can help to enhance tissue regeneration and bone consolidation. We present a case of a patient with ABC of the calcaneus treated with an endoscopic resection followed by grafting with an autologous-based matrix composed of allograft bone chips and autologous platelet-rich plasma (PRP) in semisolid and liquid states. Patient demonstrated excellent defect filling in both magnetic resonance imaging and radiologic exams and returned to pre-injury activity with no recurrence at 2 years follow-up. Endoscopic curettage together with allograft bone and autologous PRP is effective in treating ABC patients and could be a good adjuvant treatment to prevent reinjury and enhance consolidation.
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OBJECTIVE: This study investigated changes in kidney histology over time in patients with lupus nephritis (LN) undergoing immunosuppressive treatment. METHODS: Patients with proliferative±membranous LN were studied. After a diagnostic kidney biopsy (Bx1), patients had protocol biopsy 2 (Bx2) at 9 (6-15) months and protocol biopsy 3 (Bx3) at 42 (28-67) months. Kidney histological activity and chronicity indices (AI, CI) were measured. RESULTS: AI declined in a biphasic fashion, falling rapidly between Bx1 and Bx2 and then more slowly between Bx2 and Bx3. Patients were divided into those who achieved histological remission, defined as an AI=0 at Bx3 (group 1), and those with persistent histological activity (AI >0) at Bx3 (group 2). The early decline in AI was 1.6 times greater (95% CI 1.30, 1.91) in group 1 than group 2 (p=0.01). Between Bx2 and Bx3, the AI decline was 2.19-fold greater (95% CI 2.09, 2.29) in group 1 versus group 2 (p=7.34×10-5). Individual histological components of the AI resolved at different rates. Inflammatory lesions like glomerular crescents, karyorrhexis and necrosis mostly resolved by Bx2, whereas endocapillary hypercellularity, subendothelial hyaline deposits and interstitial inflammation resolved slowly, accounting for residual histological activity at biopsy 3 in group 2. In contrast, CI increased rapidly, by 0.15 units/month between Bx1 and Bx2, then plateaued. There were no differences in the rate of accumulation of chronic damage between group 1 and group 2. The increase in CI was significantly related to the severity of glomerular crescents (p=0.044), subendothelial hyaline deposits (p=0.002) and interstitial inflammation (p=0.015) at Bx1. CONCLUSIONS: LN histological activity takes months to years to resolve, providing a rationale for the need of long-term, well-tolerated maintenance immunosuppression. Despite responding, LN kidneys accrue chronic damage early during treatment. This finding provides an explanation for the association of chronic progressive kidney disease with recurrent episodes of LN.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Insuficiencia Renal Crónica , Humanos , Nefritis Lúpica/complicaciones , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/patología , Lupus Eritematoso Sistémico/patología , Riñón/patología , Glomérulos Renales/patología , InflamaciónRESUMEN
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has become a significant concern among people living with HIV (PLHIV), albeit its burden remains unclear. The primary objective of this systematic review (SR) and meta-analysis (MA) was to estimate the prevalence of NAFLD and significant fibrosis in PLHIV. The secondary objective was to determine the risk factors for NAFLD among PLHIV. METHODS: We searched MEDLINE and Scopus from inception to 30 December 2022 for peer-reviewed studies that included PLHIV and reported the prevalence of NAFLD. MA of proportions was used to estimate the pooled prevalence of NAFLD and significant fibrosis. MA of pre-calculated effect estimates examined risk factors for NAFLD in PLHIV. RESULTS: We included 24 articles published between 2009 and 2022, encompassing 6326 PLHIV. The pooled prevalence of NAFLD was 38% (95% CI: 31-45%) with high heterogeneity (I2 = 96.3%). The pooled prevalence of significant fibrosis was 13% (95% CI: 8-18%) with high heterogeneity (I2 = 92.09%). Subgroup analyses showed a NAFLD prevalence of 40% (95% CI: 24-57%) in the United States, 33% (95% CI: 31-36) in Asia, 42% (95% CI: 24-61%) in Europe and 33% (95% CI: 29-37) in South America. When stratifying by income level, NAFLD was 39% (95% CI: 31-48) prevalent in PLHIV from high-income economies and 34% in both upper-middle-income (95% CI: 31-37%) and lower-middle-income economies (95% CI: 28-41%). Higher body mass index (BMI) (OR = 1.32, 95% CI: 1.13-1.55; I2 = 89.9%), increasing triglycerides (OR = 1.48, 95% CI: 1.22-2.79; I2 = 27.2%) and dyslipidaemia (OR = 1.89, 95% CI: 1.32-2.71; I2 = 15.5%) were all associated with higher risk-adjusted odds of NAFLD in PLHIV. DISCUSSION: The burden of NAFLD and significant fibrosis in PLHIV is significant. Therefore, targeted efforts to screen and diagnose NAFLD in this population are needed. Health services for PLHIV could include ways to target NAFLD risk factors, screen for liver disease and implement interventions to treat those with significant fibrosis or more advanced stages of liver disease. Taking no action to address NAFLD in PLHIV should not be an option. CONCLUSIONS: This SR and MA found a 38% NAFLD and 13% significant fibrosis prevalence in PLHIV. Increasing triglyceride levels, higher BMI values and dyslipidaemia were associated with higher risk-adjusted odds of NAFLD among PLHIV.
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Infecciones por VIH , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Factores de Riesgo , Fibrosis , África del Sur del Sahara/epidemiología , PrevalenciaRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most important liver comorbidities in people living with HIV (PLWH). Factors that could lead to a higher prevalence of NAFLD or ease the onset of fibrosis are unclear. METHODS: Cohort study of the Spanish HIV Research Network, which comprehends 46 hospitals and more than 15,000 PLWH. Primary objectives were to assess NAFLD prevalence and liver fibrosis according to hepatic steatosis index (HSI) and NAFLD fibrosis score, respectively. Factors associated with both were analysed. RESULTS: A total of 4798 PLWH were included of whom 1461 (30.5%) showed an HSI>36; these patients had higher risk for significant fibrosis (OR 1.91; 95%CI 1.11-3.28). Factors associated with NAFLD were body mass index (OR 2.05; 95%CI 1.94-2.16) and diabetes (OR 4.68; 95%CI 2.17-10.08), while exposure to integrase strand transfer inhibitors showed a lower risk (OR 0.78; 95%CI 0.62-0.97). In patients with HSI>36, being female (OR 7.33; 95%CI 1.34-40), age (OR 1.22; 95%CI 1.11-1.34), body mass index (OR 1.35; 95%CI 1.18-1.54) and exposure to thymidine analogues (OR 75.4, 95%CI 6.9-823.5) were associated with a higher risk of significant fibrosis. However, exposure to non-nucleoside reverse transcriptase inhibitors (OR 0.12, 95%CI 0.02-0.89) and time of exposure to protease inhibitors (OR 0.97, 95%CI 0.95-1) showed a lower risk. CONCLUSION: NAFLD prevalence was high in our cohort. Patients exposed to INSTI showed a lower risk of NAFLD. In patients with hepatic steatosis, exposure to thymidine analogues had 75-fold more risk of significant fibrosis while exposure to NNRTIs reduced this risk.
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Infecciones por VIH , Enfermedad del Hígado Graso no Alcohólico , Humanos , Femenino , Masculino , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Prevalencia , Estudios de Cohortes , España/epidemiología , Cirrosis Hepática/epidemiología , Cirrosis Hepática/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicacionesRESUMEN
BACKGROUND: Chronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. PATIENTS AND METHODS: CHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. RESULTS: Three hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. CONCLUSIONS: Despite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E.
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Hepatitis E , Inmunosupresores , Inhibidores mTOR , Adulto , Humanos , Anticuerpos Antihepatitis/uso terapéutico , Hepatitis E/epidemiología , Hepatitis Crónica/epidemiología , Infecciones por VIH , Inmunoglobulina G , Inmunosupresores/efectos adversos , Cirrosis Hepática/complicaciones , Inhibidores mTOR/efectos adversos , Inhibidores mTOR/uso terapéutico , Estudios Prospectivos , Factores de Riesgo , ARN Viral/análisis , TransaminasasRESUMEN
Liver-related diseases are associated with the high levels of morbidity and mortality in people living with HIV. Between 13% and 18% of all-cause mortality in HIV-infected patients involves a liver-related damage, this being one of the main causes of death not related to acquired immunodeficiency syndrome (AIDS). People living with HIV, even when the disease is under control, are more likely to develop pathologies and complications of a liver-related origin than the general population, both due to common causes such as alcoholism, non-alcoholic fatty liver disease, hepatic viral infections and ageing, in addition to specific HIV-related processes such as antiretroviral treatment toxicity and liver damage inherent to HIV infection. On the other hand, some antiretroviral drugs may have a beneficial effect in reversing liver fibrosis in patients with HIV and chronic liver disease. This paper reviews the main risk factors associated with liver disease in people living with HIV and the role of antiretroviral therapy (ART) in this disease.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Enfermedad del Hígado Graso no Alcohólico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
DYRK1A triplication in Down's Syndrome (DS) and its overexpression in Alzheimer's Disease (AD) suggest a role for increased DYR1A activity in the abnormal metabolism of APP. Transport defects are early phenotypes in the progression of AD, which lead to APP processing impairments. However, whether DYRK1A regulates the intracellular transport and delivery of APP in human neurons remains unknown. From a proteomic dataset of human cerebral organoids treated with harmine, a DYRK1A inhibitor, we found expression changes in protein clusters associated with the control of microtubule-based transport and in close interaction with the APP vesicle. Live-imaging of APP axonal transport in human-derived neurons treated with harmine or overexpressing a dominant negative DYRK1A revealed a reduction in APP vesicle density and enhanced the stochastic behavior of retrograde vesicle transport. Moreover, harmine increased the fraction of slow segmental velocities and changed speed transitions supporting a DYRK1A-mediated effect in the exchange of active motor configuration. Contrarily, the overexpression of DYRK1A in human polarized neurons increased the axonal density of APP vesicles and enhanced the processivity of retrograde APP. In addition, increased DYRK1A activity induced faster retrograde segmental velocities together with significant changes in slow to fast anterograde and retrograde speeds transitions suggesting the facilitation of the active motor configuration. Our results highlight DYRK1A as a modulator of the axonal transport machinery driving APP intracellular distribution in neurons, and stress DYRK1A inhibition as a putative therapeutic intervention to restore APP axonal transport in DS and AD.Significance StatementAxonal transport defects are early events in the progression of neurodegenerative diseases such as Alzheimer's Disease (AD). However, the molecular mechanisms underlying transport defects remain elusive. DYRK1A kinase is triplicated in Down's Syndrome and overexpressed in AD, suggesting that DYRK1A dysfunction affects molecular pathways leading to early-onset neurodegeneration. Here, we show by live imaging of human-derived neurons that DYRK1A activity differentially regulates the intracellular trafficking of the amyloid precursor protein (APP). Further, single particle analysis revealed DYRK1A as a modulator of axonal transport and the configuration of active motors within the APP vesicle. Our work highlights DYRK1A as a regulator of APP axonal transport and metabolism; supporting DYRK1A inhibition as a therapeutic strategy to restore intracellular dynamics in AD.
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BACKGROUND: HIV-infected men who have sex with men (MSM) are at high risk to develop human papilloma virus (HPV)-related oropharyngeal cancer. The aim of our study was to assess the usefulness of a pilot oral dysplasia screening program and its correlation with an anal dysplasia screening program. METHODS: This was a prospective study with HIV-infected MSM. Oral and anal screenings were performed based on HPV determination, liquid cytology, direct and microscopy oral examinations, high-resolution anoscopy and biopsies, if necessary. RESULTS: A total of 103 patients were included. The mean age of the patients was 44.6âyears, 55.3% were smokers, and 57.3% had a history of previous anal high-grade squamous intraepithelial lesions (HSILs). The prevalence of oral HPV infections was 14% (9% HPV-high risk), the prevalence of abnormal cytology was 25.2%, and in 4.8% of the patients, oral examinations showed suspicious HSILs. Oral microscopy did not detect additional lesions that visual inspection. Five oral biopsies were performed and the results were normal. No risk factors for oral HPV infections were identified. The prevalence of anal HPV infections was 88.3% (76.7% HPV-high risk), 52.9% of the patients had altered cytology, and in 45.6% anoscopy showed changes suggestive of HSILs. Seventy-two anal biopsies were performed, detecting 25 cases of HSILs (24.3%).A poor correlation was observed between oral and anal HPV infections (κâ=â0.037). CONCLUSIONS: The prevalence of oral HPV infections, abnormal cytology and lesions in HIV-infected MSM was low, and their correlation with anal HPV-related lesions was slight. These results confirm the current barriers to oral dysplasia screening techniques.
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Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Minorías Sexuales y de Género , Adulto , Canal Anal , Neoplasias del Ano/epidemiología , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Prevalencia , Estudios ProspectivosRESUMEN
BACKGROUND: Reports on the impact of some antiretrovirals against SARS-CoV-2 infection and disease severity are conflicting. OBJECTIVES: We evaluated the effect of tenofovir as either tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with HIV (PLWH). METHODS: We conducted a propensity score-matched analysis in the prospective PISCIS cohort of PLWH (nâ=â14â978) in Catalonia, Spain. We used adjusted Cox regression models to assess the association between tenofovir and SARS-CoV-2 outcomes. RESULTS: After propensity score-matching, SARS-CoV-2 diagnosis rates were similar in TAF/FTC versus ABC/3TC recipients (11.6% versus 12.5%, Pâ=â0.256); lower among TDF/FTC versus ABC/3TC recipients (9.6% versus 12.8%, Pâ=â0.021); and lower among TDF/FTC versus TAF/FTC recipients (9.6% versus 12.1%, Pâ=â0.012). In well-adjusted logistic regression models, TAF/FTC was no longer associated with reduced SARS-CoV-2 diagnosis [adjusted odds ratio (aOR) 0.90; 95% confidence interval (CI), 0.78-1.04] or hospitalization (aOR 0.93; 95% CI, 0.60-1.43). When compared with ABC/3TC, TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or hospitalization (aOR 0.51; 95% CI, 0.15-1.70). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or associated hospitalization (aOR 0.33; 95% CI, 0.10-1.07) compared with TAF/FTC. CONCLUSIONS: TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalizations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure should not modify any preventive or therapeutic SARS-CoV-2 infection management.
Asunto(s)
Fármacos Anti-VIH , COVID-19 , Infecciones por VIH , Fármacos Anti-VIH/uso terapéutico , Prueba de COVID-19 , Emtricitabina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Humanos , Lamivudine/uso terapéutico , Puntaje de Propensión , Estudios Prospectivos , SARS-CoV-2 , Tenofovir/uso terapéuticoRESUMEN
BACKGROUND: The emergence of chemsex has raised several concerns about gay, bisexual, and other men who have sex with men's (GBMSM) health. In this study we aim to analyze illicit drugs and chemsex use, sexual behavior and sexually transmitted infections (STI) in GBMSM who attended to a sexual health clinic and to explore any potential association between drug use and STI. METHODS: We conducted an observational study between January and June 2019 among GBMSM population attending to a STI clinic in Barcelona, Spain. An anonymous self-administered questionnaire was given consecutively to all participants older than 18 years who accepted to participate. RESULTS: A total of 514 GBMSM (median age of 34 years-old) were included. The median number of sexual partners in the last year was 20. Seventy-one percent did not use condoms consistently for receptive anal intercourse. Drug abuse prevalence in the preceding year was 64.2%, and 26.5% of the individuals practiced chemsex. Gamma-hydroxibutyrate/gammabutyrolactone, poppers and methamphetamine were the most common drugs in chemsex. Chemsex was associated to group sex (OR 9.8 [95 CI: 4-24]), HIV infection (OR 2.5 [95 CI: 1.1-5.8]), taking pre-exposure prophylaxis (OR 3.2 [95 CI: 1.5-7.1]), developing gonorrhea (OR 3.7 [95 CI: 1.5-8.8]) or syphilis (OR 6.7 [95 CI: 2.4-18.7]). CONCLUSIONS: The prevalence of drug use and chemsex was high among GBMSM in Barcelona. Chemsex was associated with group sex, taking PrEP, and contracting syphilis, gonorrhea, and HIV.
Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Trastornos Relacionados con Sustancias , Masculino , Humanos , Adulto , Homosexualidad Masculina , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Sexo Inseguro , Asunción de Riesgos , Estudios Transversales , Conducta Sexual , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
Human immunodeficiency virus (HIV) establishes a persistent infection in heterogeneous cell reservoirs, which can be maintained by different mechanisms including cellular proliferation, and represent the main obstacle to curing the infection. The expression of the Fcγ receptor CD32 has been identified as a marker of the active cell reservoirs in people on antiretroviral therapy (ART), but if its expression has any role in conferring advantage for viral persistence is unknown. Here, we report that HIV-infected cells expressing CD32 have reduced susceptibility to natural killer (NK) antibody-dependent cell cytotoxicity (ADCC) by a mechanism compatible with the suboptimal binding of HIV-specific antibodies. Infected CD32 cells have increased proliferative capacity in the presence of immune complexes, and are more resistant to strategies directed to potentiate NK function. Remarkably, reactivation of the latent reservoir from antiretroviral-treated people living with HIV increases the pool of infected CD32 cells, which are largely resistant to the ADCC immune mechanism. Thus, we report the existence of reservoir cells that evade part of the NK immune response through the expression of CD32.