Incidence of Diabetes Mellitus and Associated Factors in the Era of Antiretroviral Drugs With a Low Metabolic Toxicity Profile.

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.

Sex differences in the effectiveness and tolerability of dolutegravir plus rilpivirine as a switch strategy in people living with HIV.

INTRODUCTION: Dolutegravir + rilpivirine (DTG + RPV) is an effective antiretroviral therapy regimen approved in clinical guidelines as a switch therapy for virologically suppressed people with HIV. Our study aimed to compare the effectiveness and tolerability of DTG + RPV in women and men in real-world clinical practice. METHODS: This was a retrospective analysis of treatment-experienced people with HIV from a large HIV unit who switched to DTG + RPV. We analysed treatment effectiveness, rates of adverse events and discontinuation, and metabolic changes after 48 weeks of treatment. HIV-RNA levels <50 copies/mL were analysed at 48 weeks using both intention-to treat analysis (where missing data were interpreted as failures) and per-protocol analysis (excluding those with missing data or changes due to reasons other than virological failure). Outcomes were compared between women and men based on sex at birth. RESULTS: A total of 307 patients were selected (71 women and 236 men). No transgender people were included. At baseline, women had lived with HIV infection and received antiretroviral therapy for longer than men (23.2 vs 17.4 years and 18.9 vs 14.2 years, respectively). In the intention-to-treat analysis, 74.6% (95% confidence interval [CI] 63.4-83.3%) of women and 83.5% (95% CI 78.2-87.7) of men had HIV-RNA <50 copies/mL. In the per-protocol analysis, 96.4% (95% CI 87.7-99) of women and 99% (95% CI 98.9-99.7) of men had HIV-RNA levels <50 copies/mL. Two women and two men had HIV-RNA >50 copies/mL at 48 weeks. Discontinuation due to adverse events was more frequent in women than in men: 12.7% vs 7.2% (p < 0.02). Neuropsychiatric and gastrointestinal events were the most frequently reported. A median (interquartile range) weight gain of 1.9 kg (0-4.2) in women and 1.2 kg (-1-3.1) in men was reported (median of differences between baseline visit and week 48); the remaining changes in metabolic parameters were neutral. CONCLUSIONS: DTG + RPV exhibited good and similar virological effectiveness in women and men in real-world settings. However, poorer tolerability and more treatment interruptions were observed in women.

A gut microbiome signature for HIV and metabolic dysfunction-associated steatotic liver disease.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), has emerged as an increasingly recognized problem among people living with HIV (PLWH). The gut-liver axis is considered to be strongly implicated in the pathogenesis of MASLD. We aimed to characterize the gut microbiota composition in PLWH and MASLD and compare it with that of two control groups: PLWH without MASLD and individuals with MASLD without HIV infection. Methods: We collected clinical data and stool samples from participants. Bacterial 16S rRNA genes were amplified, sequenced, and clustered into operational taxonomic unit. Alpha diversity was studied by Shannon and Simpson indexes. To study how different the gut microbiota composition is between the different groups, beta diversity estimation was evaluated by principal coordinate analysis (PCoA) using Bray-Curtis dissimilarity. To further analyze differences in microbiome composition we performed a linear discriminant analysis (LDA) effect size (LEfSe). Results: We included 30 HIV+MASLD+, 30 HIV+MASLD- and 20 HIV-MASLD+ participants. Major butyrate producers, including Faecalibacterium, Ruminococcus, and Lachnospira dominated the microbiota in all three groups. Shannon's and Simpson's diversity metrics were higher among MASLD+ individuals (Kruskal-Wallis p = 0.047). Beta diversity analysis showed distinct clustering in MASLD-, with MASLD+ participants overlapping regardless of HIV status (ADONIS significance <0.001). MASLD was associated with increased homogeneity across individuals, in contrast to that observed in the HIV+NAFDL- group, in which the dispersion was higher (Permanova test, p value <0.001; ANOSIM, p value <0.001). MASLD but not HIV determined a different microbiota structure (HIV+MASLD- vs. HIV+MASLD+, q-value = 0.002; HIV-MASLD+ vs. HIV+MASLD+, q-value = 0.930; and HIV-MASLD+ vs. HIV+MASLD-, q-value < 0.001). The most abundant genera in MASLD- were Prevotella, Bacteroides, Dialister, Acidaminococcos, Alloprevotella, and Catenibacterium. In contrast, the most enriched genera in MASLD+ were Ruminococcus, Streptococcus, Holdemanella, Blautia, and Lactobacillus. Conclusions: We found a microbiome signature linked to MASLD, which had a greater influence on the overall structure of the gut microbiota than HIV status alone.

Effect of mono/dual antiretroviral therapy on suppression of HCV and HIV during treatment of HCV infection in HIV/HCV-coinfected patients / Efecto de la terapia antirretroviral mono/dual sobre la supresión de VHC y VIH durante el tratamiento de la infección por VHC en pacientes co-infectados de VIH/VHC

OBJECTIVE: Data of hepatitis C treatment with direct-acting antivirals (DAAs) in HIV infected patients are limited to a few number of antiretroviral therapies (ART). The aim of this study was to assess the effectiveness and safety of non-conventional ART as monotherapy or dual therapy (MDT) when combined with DAA. METHODS: Retrospective review of HIV/HCV-coinfected patients treated with DAAs during one year in 3 centers. Sustained virologic response 12 weeks after therapy (SVR) and maintenance of HIV viral suppression were compared between patients receiving triple ART (TT) or MDT. RESULTS: Overall 485 patients were included (359 receiving TT and 126 MDT). HCV SVR was 93.4% (95%CI, 90.8% to 95.3%) in the intention-to-treat analysis without differences between groups: 92.8% on TT vs 95.2% on MDT (p = 0.3). HCV virological failure was associated with lower CD4 + cell count at baseline (for every 100-cell/μl increment: OR, 0.8; 95%CI, 0.7-0.9; p = 0.01) and with liver stiffness (for every 10-unit increment: OR, 1.5; 95%CI 1.2-1.8; p < 0.01). HIV-RNA during HCV treatment or 12 weeks after was detectable in 23 patients on TT (6.6%) and 9 (7.2%) patients on MDT (p = 0.8). The median (IQR) change in CD4 + cell count was not significantly different between the groups: 15 (-55 to 115) in TT vs -12 (-68 to 133) cells/μl in MDT (p = 0.8). CONCLUSION: DAAs obtain high rates of SVR among HIV/HCV-coinfected patients independently of whether TT or non-conventional ART is used. Suppression of HIV was maintained in both groups

OBJETIVO: Los datos sobre el tratamiento de la hepatitis C con antivirales de acción directa (AAD) en los pacientes infectados por VIH se limitan a un escaso número de terapias antirretrovirales (TARV). El objetivo de este estudio fue valorar la efectividad y seguridad de las TARV no convencionales, como monoterapia y terapia dual (MDT), al combinarse con AAD. MÉTODOS: Revisión retrospectiva de pacientes co-infectados por VIH/VHC, tratados con AAD durante un año en 3 centros. Se comparó la respuesta virológica sostenida (RVS) a las 12 semanas de la terapia, y el mantenimiento de la supresión viral del VIH, entre los pacientes que recibieron triple TARV o MDT. RESULTADOS: Se incluyó a un total de 485 pacientes (359 que recibieron triple TARV y 126 que recibieron MDT). La RVS de VHC fue del 93,4% (IC 95%: 90,8-95,3%) en el análisis por intención de tratar, sin diferencias entre grupos: 92,8% en el grupo triple TARV vs. 95,2% en el grupo MDT (p = 0,3). El fracaso virológico de VHC se asoció a un menor recuento basal de células CD4+ (para cada incremento de 100células/μl: OR: 0,8; IC 95%: 0,7-0,9; p = 0,01) y a la rigidez hepática (para cada incremento de 10 unidades: OR: 1,5; IC 95%: 1,2-1,8; p < 0,01). El ARN-VIH durante el tratamiento de VHC, o transcurridas 12 semanas, fue detectable en 23 pacientes en el grupo triple TARV (6,6%) y 9 (7,2%) pacientes en el grupo MDT (p = 0,8). El cambio medio (RIC) en el recuento de células CD4 + no fue significativamente diferente entre ambos grupos: 15 (de -55-115) en el grupo triple TARV vs. -12 (de -68-133) células/μl en el grupo MDT (p = 0,8). CONCLUSIÓN: Los AAD obtienen tasas altas de RVS entre los pacientes co-infectados de VIH/VHC, independientemente de si se utiliza triple TARV o TARV no convencional. La supresión de VIH se mantuvo en ambos grupos

Psoriasis e hígado graso: una sinergia perjudicial / Psoriasis and fatty liver: a harmful synergy

Numerosos estudios epidemiológicos confirman la mayor prevalencia de la enfermedad hepática grasa no alcohólica en la psoriasis grave, con un riesgo de más del doble respecto a la población sin psoriasis (odds ratio [OR] 2,15). En estos pacientes, la enfermedad hepática es más grave que en controles sin psoriasis, guardando, a su vez, relación con la gravedad de la psoriasis. De forma recíproca, los pacientes con hígado graso presentan una mayor gravedad de la psoriasis. Esta perjudicial sinergia tiene un origen patogénico común, resultado de la frecuente asociación de las dos enfermedades a resistencia insulínica y síndrome metabólico, el cual se manifiesta con mayor intensidad cuando coexisten ambas que si lo hacen por separado. Como segundo factor, psoriasis e hígado graso comparten un trasfondo inflamatorio crónico mediado por citoquinas, con desequilibrio entre las proinflamatorias y las antiinflamatorias, del que se retroalimentan mutuamente. El dermatólogo debe ser el principal detector de la hepatopatía, valorando de forma específica a sus pacientes que presenten factores de síndrome metabólico. El hepatólogo debe ser consciente de la mayor gravedad de estos pacientes. Diversos medicamentos, como acitretino, ciclosporina y metotrexato, pueden resultar perjudiciales para la hepatopatía. Los medicamentos biológicos resultan seguros en el paciente con enfermedad hepática crónica. Hepatólogos y dermatólogos, de forma conjunta, deben valorar cuidadosamente la mejor opción terapéutica en cada paciente dependiendo de la gravedad de ambas enfermedades, evitando en lo posible medicamentos hepatotóxicos y optando por opciones que, incluso, pudieran tener un beneficio compartido en ambas enfermedades

Numerous epidemiology studies confirm the increasing prevalence of non-alcoholic fatty liver disease in severe psoriasis, with more than double the risk reported for patients without psoriasis (odds ratio [OR] 2.15). Liver disease is more severe in patients with psoriasis than in controls without psoriasis and is associated with the severity. Similarly, patients with fatty liver disease have more severe psoriasis. This harmful synergy has a common pathogenic origin, resulting from the frequent association between both diseases, insulin resistance and the metabolic syndrome. The disease manifests with a greater intensity when both conditions co-occur than when each manifests separately. Furthermore, psoriasis and fatty liver also have a common cytokine-mediated inflammatory background, which involves an imbalance between pro-inflammatory and anti-inflammatory cytokines. In fact, each disease plays a role in the course of the other. The dermatologist should usually detect liver disease after a specific assessment of patients who present with the metabolic syndrome. The hepatologist should be aware of the more severe condition of these patients. Various medications, such as acitretin, cyclosporine and methotrexate may prove harmful for patients with liver disease. Biologics have proven to be safe in patients with chronic liver disease. Hepatologists and dermatologists should work together to ensure the careful evaluation of the optimal therapy for each patient depending on the severity of both diseases, taking care to avoid, where possible, hepatotoxic drugs and select options that may even have a shared benefit for both diseases

Enfermedad desmielinizante en pacientes infectados por el virus de la inmunodeficiencia humana sin inmunodepresión severa / Demyelinating disease in human immunodeficiency virus-infected patients without severe immunodepression

Objetivo Se analizaron los casos de lesiones desmielinizantes múltiples en pacientes con infección VIH sin inmunodepresión grave. Métodos Se realizó una búsqueda a través de una base de datos informatizada y se seleccionaron aquellos pacientes con linfocitos CD4 superior a 200 (..) (AU)

Objective Human immunodeficiency virus (HIV) infected patients who did not have severe immunodepression were analysed for multiple demyelinating lesions. Methods Patients with a CD4 greater than (..) AU)

Respuesta de los autores: Monitorizacion ambulatoria de la presion arterial en el paciente VIH / Author’s reply: Outpatient blood pressure monitoring of the HIV patient

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Hipertensión arterial, infección por el virus de la inmunodeficiencia humana y tratamiento antirretrovírico de gran actividad / Hypertension, HIV infection, and highly active antiretrovíric therapy

El tratamiento antirretrovírico de gran actividad (TARGA) ha conseguido una drástica reducción de la mortalidad de los pacientes infectados por el virus de la inmunodeficiencia humana (VIH). A su vez, el TARGA ha producido un incremento en las alteraciones metabólicas que provocan una aterosclerosis acelerada. La hipertensión arterial (HTA) es uno de los principales factores de riesgo cardiovascular. Sin embargo, el posible efecto del TARGA sobre la presión arterial (PA) ha sido poco estudiado. Hay dudas sobre si la propia infección crónica o el TARGA tienen un papel etiológico en la aparición de HTA. En este trabajo se revisan los estudios publicados hasta la fecha sobre la relación entre la infección por VIH y la HTA. El efecto del TARGA sobre la PA parece ser modesto y mediado por los cambios metabólicos que induce el tratamiento antirretrovírico (AU)

The decline in mortality resulting from the use of highly active antiretroviral therapy (HAART) has been accompanied by an increase in metabolic complications that produce accelerated atherosclerosis. Hypertension is one of the most important cardiovascular risk factors. Little is known about the impact of HAART on blood pressure, and it is uncertain whether chronic HIV infection or HAART have a role in the development of hypertension. In this study, the research on the relationships between hypertension and HIV infection published to date is reviewed. Antiretroviral therapy appears to have a modest impact on blood pressure and to be partially mediated by the metabolic changes occurring with this treatment (AU)

Factores asociados con esteatosis hepática en pacientes coinfectados por los virus de la inmunodeficiencia humana y de la hepatitis C / Factors associated with hepatic steatosis in human immunodeficiency virus and hepatits C virus coinfected patients

Fundamento y objetivo: determinar la prevalencia y los factores asociados con la presencia de esteatosis hepática y con su intensidad en los pacientes coinfectados por los virus de la inmunodeficiencia humana (VIH) y de la hepatitis C (VHC).Pacientes y método: se han evaluado las biopsias hepáticas de 163 pacientes coinfectados por el VIH y VHC. Se excluyó a aquéllos con antígeno de superficie del virus de la hepatitis B y tratamiento previo del VHC. El grado de esteatosis se evaluó según el porcentaje de hepatocitos afectados. La actividad necroinflamatoria y el grado de fibrosis se clasificaron según el sistema de Scheuer. Mediante regresión logística se valoraron los factores asociados con la presencia e intensidad de la esteatosis en la biopsia. Resultados: un 65% de las biopsias presentaba esteatosis, que era moderada-intensa (>30% de los hepatocitos) en un 17%. Un 78,5% de los pacientes recibía tratamiento antirretroviral de gran actividad en el momento de realizar la biopsia. Los factores asociados con la presencia de esteatosis fueron: el peso corporal, el consumo de alcohol, la presencia de fibrosis avanzada, la exposición a estavudina y la ausencia de exposición a lopinavir/ritonavir. Los factores asociados con la intensidad de la esteatosis (>30% de hepatocitos) fueron: el consumo de alcohol, el genotipo 3 del VHC, la carga vírica del VHC mayor de 1.400.000 copias de ARN/ml y la presencia de fibrosis avanzada. Conclusiones: la presencia de esteatosis y su intensidad se asociaron a un mayor grado de fibrosis hepática en los pacientes coinfectados por el VIH y VHC. El peso, el consumo de alcohol y el tratamiento antirretroviral (tratamiento con estavudina y ausencia de tratamiento con lopinavir/ritonavir) son factores modificables que se asociaron a la presencia de esteatosis. Las características de la infección del VHC estaban asociadas a la intensidad de la esteatosis en esta población (AU)

Background and objective: To determinate the prevalence and factors associated with hepatic steatosis and severity of steatos is in human immunodeficiency virus (HIV) and hepatits C virus (HCV) coinfected patients. Patients and method: Liver histology was assessed in 163 HIV-HCV coinfected patients. Exclusion criteria included positive hepatitis B surface antigen and prior anti-HCV therapy. Steatosis was scored by a single pathologist according to the percentage of affected hepatocytes. Necroinflammatory activity and fibrosis was scored by the Scheuer system. Logistic regression analyses were used to evaluate variables associated with hepatic steatosis. Results: Steatosis was present in 65% of biopsy samples. Moderate-severe steatosis (>30% of hepatocytes) was detected in 17% of patients. 78.5% of patients were under high active antiretroviral therapy at the time of biopsy. In a multivariate analysis, steatosis was associated with body weight, alcohol, advanced fibrosis, stavudine use and non-use of lopinavir/ritonavir. In a multivariate analysis, severity of steatosis (>30% of hepatocytes) was associated with alcohol, HCV genotype 3, HCV load >1,400,000 copies/ml and advanced fibrosis. Conclusions: The presence of hepatic steatosis and severity of steatosis were associated with advanced fibrosis in patients coinfected with HIV and HCV. Body weight, consumption of alcohol and antiretroviral therapy (stavudine use and absence of exposure to lopinavir/ritonavir) were modifiable factors associated with the presence of steatosis. Characteristics of HCV infection were associated with the severity of steatosis in this population (AU)

Relación entre fibrosis hepática medida por elastografía transitoria y valores de linfocitos CD4+ en sangre periférica / Relationship between hepatic fibrosis measured by transient elastography and peripheral blood CD4+ lymphocyte values

La fibrosis hepática avanzada disminuye la cifra absoluta de linfocitos CD4+ en pacientes con infección por el virus de la inmunodeficiencia humana (VIH). Se desconoce si existe una correlación entre rigidez hepática medida por elastografía transitoria y la cifra absoluta de linfocitosCD4+.Se realiza análisis de la correlación entre resultados de elastografía transitoria y cifras de linfocitos CD4+ en223 sujetos coinfectados por VIH y virus hepatotropos. Los valores absolutos de linfocitos CD4+ fueron menores en pacientes con fibrosis significativa (384 céls./ml frentea 431 céls./ml; p = 0,023) y en pacientes con fibrosisavanzada (330 céls./ml frente a 431 céls./ml; p = 0,002).Existe una asociación significativa entre la fibrosishepática medida por elastografía transitoria y los valores absolutos de linfocitos CD4+ en pacientes coinfectados por VIH y virus hepatotropos (AU)

Advanced hepatic fibrosis decreases absoluteCD4+ lymphocyte count in HIV-infected patients. The correlation between hepatic stiffness measured by transient elastography and absolute CD4+ lymphocytecount is unknown. Analysis of the correlation between transient elastography parameters and absolute CD4+ lymphocyte count in223 HIV-infected patients with chronic viral hepatitis. As compared to patients without significant fibrosis, absolute CD4+ cell count was lower in patients with significant hepatic fibrosis (384 cel/mL vs. 431 cel/mL;P = 0.023) and in patients with advanced hepatic fibrosis(330 cel/mL vs. 431 cel/mL; P = 0.002). There is a significant association between hepatic stiffness measured by transient elastography and absoluteCD4 lymphocyte count in HIV-infected patients with chronic viral hepatitis (AU)