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BACKGROUND: Studies on switching to tenofovir alafenamide (TAF)-based regimens raise concerns about a worse metabolic profile in people with HIV, even though most received tenofovir disoproxil fumarate (TDF) in their previous regimen. This study aims to evaluate changes in lipid fractions, glucose, and serum markers for hepatic steatosis (HS) after switching from a TDF- or TAF-sparing regimen to bictegravir/emtricitabine/TAF (B/F/TAF). METHODS: We performed a retrospective cohort study of people with HIV who switched to B/F/TAF from TDF- or TAF-sparing regimens between January 2019 and May 2022 with at least 6 months of follow-up. The primary endpoint was the absolute change in lipid fractions at 6 months. Secondary outcomes were changes in lipid fractions at 12 months and changes in other metabolic parameters (glucose, creatinine, and HS based on the triglyceride-to-glucose [TyG] ratio at 6 and 12 months). Changes were analysed using mixed linear regression models with random intercept and time as a fixed effect. RESULTS: The study included 259 people with HIV (median age 55 [interquartile range (IQR) 47-60] years; 80% male; 88% Caucasian; CD4+ T-cell count 675 [IQR 450-880] cells/mm3; 84.3% HIV-RNA <50 copies/mL). In total, 63 patients (30%) had hypertension, 93 (44%) dyslipidaemia, 30 (14%) diabetes, and 45% obesity/overweight. Most (60%) switched from integrase inhibitor-based regimens, and 21% switched from a boosted regimen. At 6 months, significant reductions were observed in total cholesterol (-7.64 mg/dL [95% confidence interval (CI) -13.52 to -1.76; p = 0.002]), triglycerides (-23.4 [95% CI -42.07 to -4.65]; p = 0.003), and TyG ratio (-0.14 [95% CI -0.23 to -0.05]; p < 0.001). CONCLUSION: In our real-life cohort, the effect of switching TDF-/TAF-sparing regimens to triple therapy with B/F/TAF improved total cholesterol, triglycerides, and serum markers of HS at 6 months and was neutral for the remaining metabolic parameters at 12 months.
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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)<â50 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 VLâ<â50 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/TAFâ+âdarunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.
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Fármacos Anti-VIH , Infecciones por VIH , Adulto , Femenino , Humanos , Masculino , Adenina/uso terapéutico , Alanina/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Antirretrovirales/uso terapéutico , Cobicistat/uso terapéutico , Darunavir/uso terapéutico , ADN/uso terapéutico , Emtricitabina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Estudios Prospectivos , Espectrometría de Masas en TándemRESUMEN
INTRODUCTION: The use of tenofovir alafenamide (TAF) has been associated with increased cholesterol and body weight. Real-life data on the metabolic effects of switching from a TAF-based triple regimen to a dolutegravir (DTG)-based two-drug regimen (2-DR) are scarce. METHODS: A retrospective cohort study of patients who have switched from a triple TAF-based regimen to a 2-DR [DTG-lamivudine (DTG-3TC) or DTG- rilpivirine (DTG-RPV]) with at least 6 months of follow-up. The primary endpoint was the absolute change in lipid fractions at 6 months. Secondary outcomes were percentage changes in lipid fraction, effectiveness and safety at 6 and 12 months [intention to treat (ITT), missing = failures]. RESULTS: A total of 118 patients (87 on DTG-3TC, 31 on DTG-RPV) were included. Median age was 51 years (interquartile range: 43-59), 86% were male, CD4 T-cell count was 692 cells/µL, and 98% viral load (VL) < 50 copies/mL. At 6 months there was a decrease in total and low-density lipoprotein cholesterol of 10.7 mg/dL [95% confidence interval (CI): 2.2-19.1; p ≤ 0.001] and 8.3 mg/dL (95% CI: 0.74-15.9; p = 0.026), respectively. There was a reduction in cardiovascular risk from 4.5% at baseline to 4% at 12 months (p = 0.040). Virological effectiveness as determined by ITT analysis was 85.6% at 6 months and 66.1% at 12 months. Seven patients (5.9%) withdrew from the 2-DR and there was no virological failure. CONCLUSIONS: In real life, switching from a triple regimen with TAF to DTG-3TC or DTG-RPV dual therapy improves the lipid profile and is an effective and well-tolerated strategy.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Masculino , Persona de Mediana Edad , Femenino , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Lamivudine/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Oxazinas/uso terapéutico , Adenina/uso terapéutico , Colesterol , LípidosRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV) infection induces epigenetic age acceleration (EAA), but it remains unclear whether epigenetic aging continues to accelerate during successful antiretroviral therapy (ART) and prolonged virological suppression. METHODS: We longitudinally analyzed 63 long-term aviremic HIV-infected adults. Using blood DNA methylation patterns, we calculated EAA measures based on 3 epigenetic clocks (Horvath's clock, PhenoAge, and GrimAge). We recorded the emergence of serious AIDS-related and non-AIDS-related events throughout the study to assess its association with EAA. RESULTS: All participants were on stable ART and were virologically suppressed. After 4 years of follow-up, PhenoAge-EAA and GrimAge-EAA showed no differences, whereas Horvath-EAA slightly decreased (median difference, -0.53 years; P = .015). Longitudinal changes in EAA measures were independent of changes in CD4 cell counts, the ART regimen, or other HIV-related factors. Nineteen percent of participants experienced a serious clinical event during the study. Horvath-EAA was significantly higher at baseline in participants with clinical events (P = .027). After adjusting for confounders, we found a trend toward an association of higher levels of all EAA measures at baseline with serious clinical events. CONCLUSIONS: Epigenetic aging did not accelerate in long-term aviremic HIV-infected adults after 4 years of successful ART. EAA measures deserve further study as potential tools for predicting clinical events.
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Envejecimiento/genética , Terapia Antirretroviral Altamente Activa/métodos , Epigénesis Genética , Infecciones por VIH/tratamiento farmacológico , Adulto , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa/efectos adversos , Epigenómica , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana EdadRESUMEN
Background: Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown. Methods: A prospective cohort of human immunodeficiency virus (HIV)-infected participants with suppressed virological replication was recruited to compare whole-blood telomere length (measured by quantitative multiplex polymerase chain reaction analysis) in participants with current exposure to tenofovir disoproxil fumarate (TDF) to that in participants never exposed to TDF. Results: A total of 172 participants were included: 67 were in the TDF group, and 105 were in the non-TDF group (75 were receiving 2 nucleosides [of whom 69 were receiving abacavir], 25 were receiving a nucleos[t]ide reverse transcriptase inhibitor [N{t}RTI]-sparing regimen, and 5 were receiving lamivudine as the only nucleoside). After 2 years, the mean blood telomere length increased significantly in the whole cohort. The TDF group had significantly smaller gains in telomere length than the non-TDF group. In the analysis restricted to participants receiving N(t)RTIs, TDF exposure was not associated with an independent negative effect. In the non-TDF group, participants treated with 2 nucleosides also had significantly smaller gains in telomere length than those receiving N(t)RTI-sparing regimens or lamivudine as the only nucleoside. Discussion: In HIV-infected adults with prolonged virological suppression, treatment with TDF or abacavir was associated with smaller gains in blood telomere length after 2 years of follow-up.
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Infecciones por VIH , Inhibidores de la Transcriptasa Inversa , Telómero/efectos de los fármacos , Adulto , Didesoxinucleósidos/farmacología , Didesoxinucleósidos/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Telomerasa , Tenofovir/farmacología , Tenofovir/uso terapéutico , Carga ViralRESUMEN
INTRODUCTION: The objective of the study is to validate the relevant GESIDA quality indicators for HIV infection, assessing the reliability, feasibility and adherence to them. METHODS: The reliability was evaluated using the reproducibility of 6 indicators in peer review, with the second observer being an outsider. The feasibility and measurement of the level of adherence to the 22 indicators was conducted with annual fragmented retrospective collection of information from specific databases or the clinical charts of the nine participating hospitals. RESULTS: Reliability was very high, with interobserver agreement levels higher than 95% in 5 of the 6 indicators. The median time to achieve the indicators ranged between 5 and 600minutes, but could be achieved progressively from specific databases, enabling obtaining them automatically. As regards adherence to the indicators related with the initial evaluation of the patients, instructions and suitability of the guidelines for ART, adherence to ART, follow-up in clinics, and achieve an undetectable HIV by PCR at week 48 of the ART. Indicators of quality related to the prevention of opportunistic infections and control of comorbidities, the standards set were not achieved, and significant heterogeneity was observed between hospitals. CONCLUSION: The GESIDA quality indicators of HIV infection enabled the relevant indicators to be feasibly and reliably measured, and should be collected in all the units that care for patients with HIV infection.
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Infecciones por VIH/terapia , Indicadores de Calidad de la Atención de Salud/normas , Estudios de Factibilidad , Infecciones por VIH/epidemiología , Humanos , Reproducibilidad de los Resultados , Estudios Retrospectivos , España/epidemiologíaRESUMEN
Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome.
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Infecciones por VIH/complicaciones , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/prevención & control , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Terapia Antirretroviral Altamente Activa , Infecciones Bacterianas/tratamiento farmacológico , Coinfección , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/tratamiento farmacológico , Síndrome Inflamatorio de Reconstitución Inmune/prevención & control , Infecciones por Mycobacterium/tratamiento farmacológico , Infecciones por Mycobacterium/prevención & control , Micosis/tratamiento farmacológico , Micosis/prevención & control , Infecciones Oportunistas/etiología , Enfermedades Parasitarias/tratamiento farmacológico , Enfermedades Parasitarias/prevención & control , Virosis/tratamiento farmacológico , Virosis/prevención & controlRESUMEN
Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection.
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Infecciones por VIH/complicaciones , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/prevención & control , Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/prevención & control , Coinfección/tratamiento farmacológico , Coinfección/prevención & control , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/diagnóstico , Síndrome Inflamatorio de Reconstitución Inmune/tratamiento farmacológico , Síndrome Inflamatorio de Reconstitución Inmune/prevención & control , Micosis/tratamiento farmacológico , Micosis/prevención & control , Enfermedades Parasitarias/tratamiento farmacológico , Enfermedades Parasitarias/prevención & control , Virosis/tratamiento farmacológico , Virosis/prevención & controlRESUMEN
This consensus document has been prepared by a panel of experts appointed by GeSIDA. This paper reviews the recommendations on the most important non-AIDS defining malignancies that can affect patients living with AIDS. Lung cancer, hepatocellular carcinoma, anal carcinoma and other less frequent malignancies such as breast, prostate, vagina or colon cancers are reviewed. The aim of the recommendations is to make clinicians who attend to this patients aware of how to prevent, diagnose and treat this diseases. The recommendations for the use of antiretroviral therapy when the patient develops a malignancy are also presented. In support of the recommendations we have used the modified criteria of the Infectious Diseases Society of America.
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Infecciones por VIH/complicaciones , Neoplasias/terapia , Algoritmos , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Manejo de la Enfermedad , Medicina Basada en la Evidencia , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Huésped Inmunocomprometido , Masculino , Neoplasias/complicaciones , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/prevención & control , Infecciones Tumorales por Virus/complicacionesRESUMEN
Liver fibrosis is a key determinant of the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Its increasing prevalence and a lack of effective treatments make it a major health problem worldwide, particularly in people living with HIV, among whom the prevalence of advanced fibrosis is higher. We have published preclinical data showing that Rilpivirine (RPV), a widely used anti-HIV drug, selectively triggers hepatic stellate cell (HSC) inactivation and apoptosis through signal transducer and activator of transcription (STAT)1-mediated pathways, effects that clearly attenuate liver fibrosis and promote regeneration. We performed a retrospective, cross-sectional study of RPV-induced effects on steatosis, inflammation, and fibrosis in liver biopsies from well-controlled HIV-infected subjects diagnosed with MASLD. Patients on RPV exhibited similar levels of HIV-related parameters to those not receiving this drug, while showing a tendency toward improved liver function and lipid profile, as well as an enhanced activation of STAT1 in hepatic non-parenchymal cells in those with identified liver injury. This protective effect, promoting STAT1-dependent HSC inactivation, was observed at different stages of MASLD. Our results suggest that RPV-based therapy is especially indicated in HIV-infected patients with MASLD-derived liver injury and highlight the potential of RPV as a new therapeutic strategy for liver diseases.
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Several factors are involved in the control of HIV transcription/replication, including epigenetic modifications at the promoter level. Analysis of the HIV long terminal repeat (LTR) methylation status in infected patients controlling viremia is scarce. Herein, we show a higher degree of DNA methylation in the 5'-LTR of long-term nonprogressor and elite controller (LTNP/EC) versus progressor patients and a positive correlation with time of infection, indicating a certain contribution of HIV LTR silencing in reducing the number of replicating viruses which may account for a delayed progression.
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Metilación de ADN , Epigénesis Genética/genética , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Viremia/prevención & control , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/sangre , Duplicado del Terminal Largo de VIH/genética , Sobrevivientes de VIH a Largo Plazo , Humanos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/virología , Filogenia , Provirus/genética , Viremia/genéticaRESUMEN
OBJECTIVE: To evaluate the safety and efficacy of abacavir/lamivudine (ABC/3TC) plus darunavir/ritonavir (DRV-RTV) in experienced patients. METHODS: The study was conducted in Spain in 6 hospital clinics and involved HIV-positive patients who needed to change their antiretroviral treatment (ART) for several reasons. They started fixed-dose combination (FDC) ABC/3TC (600 mg/300 mg), DRV (400 mg 2 tablets qd), and RTV (100 mg) from January 2010 to April 2012. The patients were evaluated at baseline and at intervals of 3 to 6 months, and at least once at the end of the follow-up. Adverse events (AEs), concurrent medications, HIV-associated conditions, and adherence were also assessed at each visit. RESULTS: Seventy-six patients were included from 6 sites (60 male). Median CD4 cell count was 479/mm3, and the median time on follow-up was 10.1 months. Thirty-eight patients (50%) have reached 48 weeks of follow-up and 32 (84.2 %) have achieved HIV RNA <50 copies/mL in this period. Immunological recovery was observed with a median CD4 count increase of 119 cells/mm3 by week 48. There were no patients who discontinued the study treatment due to AEs, and all the toxicities that lead to change ART at baseline were resolved or improved substantially. CONCLUSION: This study showed that the study regimen provided consistent antiviral and immunological responses until 48 weeks. The antiretroviral effect of the regimen was observed in subsets of patients evaluated, including those with high baseline HIV-1 RNA levels and virological failure and those with switching, with little or no difference across subgroups.
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Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/administración & dosificación , Recuento de Linfocito CD4 , Darunavir , Didesoxinucleósidos/administración & dosificación , Didesoxinucleósidos/uso terapéutico , Esquema de Medicación , Combinación de Medicamentos , Quimioterapia Combinada , Humanos , Ritonavir/administración & dosificación , Ritonavir/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéuticoRESUMEN
Here, we aim to describe mental health (MH) in a cohort of children, adolescents, and young adults living with perinatally acquired HIV (PHIV) in Spain and explore the treatment gap for mental disorders. We also aim to analyze the potential association between MH issues to psychosocial risk factors (PSRFs) and identify management priorities. We conducted a descriptive transversal study that included all cases of PHIV under follow-up in a reference hospital in Madrid. The study included patients undergoing follow-up in the pediatric outpatient clinic and youths transferred from pediatric to adult care units after 1997. Epidemiological, clinical, immunovirological, and treatment-related data were collected, including PSRF and adverse childhood experiences (ACEs). Of the 72 patients undergoing follow-up, 43 (59.7%) had already been transferred to the adult outpatient clinic. The patients' median age was 25 years (IQR 18-29), and 54.2% were women. Most patients were undergoing treatment (94.6%) and were virologically suppressed (84.7%). Although MH issues were present in 30 patients (41.7%), only 17 (56.7%) had been referred for evaluation to the Department of Mental Health, and only 9 (30%) had received a MH diagnosis. PSRFs were common (32% of participants had at least one PSRF) and were associated with MH issues and adherence issues (all p < 0.05). A multidisciplinary approach to address the psychological factors and social determinants of health is urgently needed, particularly during important life development stages, such as adolescence.
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PURPOSE: To determine the clinical, epidemiological and prognostic factors of HIV-infected patients with influenza A H1N1 admitted to hospital. METHODS: The study population was HIV infected patients with confirmed influenza infection admitted to hospital in a multicenter cohort. We analyzed demographic data, comorbid conditions, severe events (bronchopneumonia, respiratory insufficiency, respiratory distress, sepsis, admission to intensive care unit, death) and outcome. Data were analyzed using descriptive statistics. Proportions were compared using the χ(2) test or Fisher exact test, when applicable. Quantitative variables were compared using the Student t test or Mann-Whitney test. Prognostic impact was analyzed using logistic regression. RESULTS: A total of 43 patients, of whom 62.8% were male, were included from 22 hospitals. The mean age was 43.3 years (interquartile range [IQR], 38.4-48.4). HIV was diagnosed for a mean of 14.5 years (IQR, 8.4-20.3). CD4 lymphocyte was <200 cells/µL in 38%; 85.7% were on antiretroviral therapy, and 66.7% virologically suppressed. Comorbid conditions were hepatitis B or C (74.4%), smoking (67.4%), chronic obstructive pulmonary disease (30.2%), asthma (14%), and obesity (8.6%). Seven patients had received seasonal influenza vaccination, and 2 the H1N1 vaccine. Cough (100%), fever (93%), gastrointestinal disorders (27.9%) or general--myalgia, general malaise--(67.4%) were the presenting symptoms. These were severe in 24 (55.8%) with 7 (16.3%) requiring intensive care. Two patients died. A lower CD4 lymphocyte count was associated with bacterial infection (P=.063) and longer hospital stay (P=.007). Early oseltamivir reduced severe cases (OR, 4.5; 1.1-18.3; P=.035). CONCLUSIONS: HIV-infected patients admitted to hospital due to influenza A H1N1 had severe morbidity. Low CD4 lymphocytes correlated with longer hospitalization and bacterial infections. Early oseltamivir treatment reduced severe symptoms.
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Infecciones por VIH/epidemiología , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/epidemiología , Pandemias , Adulto , Fármacos Anti-VIH/uso terapéutico , Antivirales/uso terapéutico , Recuento de Linfocito CD4 , Estudios de Cohortes , Comorbilidad , Femenino , Infecciones por VIH/tratamiento farmacológico , Mortalidad Hospitalaria , Humanos , Vacunas contra la Influenza , Gripe Humana/tratamiento farmacológico , Pacientes Internos/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Oseltamivir/uso terapéutico , Enfermedades Respiratorias/epidemiología , Sepsis/epidemiología , Fumar/epidemiología , España/epidemiología , Evaluación de Síntomas , Resultado del Tratamiento , Vacunación/estadística & datos numéricosRESUMEN
PURPOSE: To review the incidence and characteristics of acute hepatitis B (AHB) in a large cohort of HIV infected persons from a low prevalence region during the last two decades. METHODS: Retrospective review of an HIV Cohort from a single reference centre in Madrid, Spain, between 2000 and 2018. AHB was diagnosed in persons with newly acquired HBAgS and acute hepatitis with positive IgM anti-HBc. RESULTS: Out of 5443 HIV+ patients in our cohort (3098 anti-HBc negative), 18 developed AHB from 2000 to 2018. The global incidence was 0.02 (0.01-0.04) per 100 patient-year in the entire population and 0.06 (0.01-0.1) per 100 patient-year in the anti-HBc negative population. A statistically significant decrease in AHB incidence was observed during these years (ß=-0.006; p=0.047). All 18 patients diagnosed with AHB were men, the majority (16) occurred in men who have sex with men. AHB was observed in 4 persons previously unresponsive to vaccination. Regarding antiretroviral treatment (ART), 15 were not receiving ART, two persons were on ART with any HBV active drugs and one person had lamivudine in the regimen. Two persons (11%) developed chronic hepatitis B. There were no cases of fulminant hepatitis. CONCLUSION: The incidence of AHB in HIV positive persons in our cohort was low and shows a progressive decline in the last 20 years. Cases occurred in persons not protected against VHB: not vaccinated or non-responders to vaccine that were not receiving tenofovir.
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Infecciones por VIH , Hepatitis B , Minorías Sexuales y de Género , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis B/uso terapéutico , Homosexualidad Masculina , Humanos , MasculinoRESUMEN
INTRODUCTION: Few clinical trials and cohort studies have evaluated the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV (PWH) with preexisting M184V/I or other nucleos(t)ide reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs). Real-world data are also scarce. METHODS: Retrospective review of treatment-experienced patients who started B/F/TAF in a cohort of PWH. HIV-RNA less than 50âcopies/ml was analyzed at 48âweeks in an intention-to-treat (ITT) analysis (missing=failure) and per protocol analysis (patients with missing data or changes for reasons other than virological failure were excluded). Results were compared in patients with and without previous NRTI-RAMs. RESULTS: Five hundred and six PWH were included (16.2% women). Median age and time with HIV infection were 52.3 and 18.9âyears, respectively. At baseline, viral load was less than 50âcopies/ml in 440 patients (86.6%). Overall, 69 (13.6%) participants had documented preexisting NRTI-RAMs: 57 (11.2%) M184V/I and 30 (5.9%) tenofovir RAMs. In the ITT analysis, 83% (420/506) had HIV-RNA less than 50âcopies/ml [82.2% (359/437) and 88.4% (61/69) in persons without and with NRTI-RAMs, respectively ( P â=â0.2)]. In the per protocol analysis 94.2% (420/445) had HIV-RNA less than 50âcopies/ml [94.4% (359/380) vs. 93.8% (61/65); P â=â0.2]. A total of 61 participants were excluded from the per protocol analysis (23 missing data, 19 discontinued B/F/TAF because of toxicity, 13 for other reasons, and 6 died). CONCLUSION: Switching to B/F/TAF is well tolerated and effective in the real-world setting, even in patients with preexisting NRTI RAMs, such as M184V and RAMs conferring resistance to tenofovir. These results confirm the robustness of this combination.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Femenino , Masculino , Humanos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Emtricitabina , VIH-1/genética , Adenina , Tenofovir/uso terapéutico , Tenofovir/farmacología , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Combinación de Medicamentos , ARN/uso terapéuticoRESUMEN
PURPOSE: To review the incidence and characteristics of acute hepatitis B (AHB) in a large cohort of HIV infected persons from a low prevalence region during the last two decades. METHODS: Retrospective review of an HIV Cohort from a single reference centre in Madrid, Spain, between 2000 and 2018. AHB was diagnosed in persons with newly acquired HBAgS and acute hepatitis with positive IgM anti-HBc. RESULTS: Out of 5443 HIV+ patients in our cohort (3098 anti-HBc negative), 18 developed AHB from 2000 to 2018. The global incidence was 0.02 (0.01-0.04) per 100 patient-year in the entire population and 0.06 (0.01-0.1) per 100 patient-year in the anti-HBc negative population. A statistically significant decrease in AHB incidence was observed during these years (ß=-0.006; p=0.047). All 18 patients diagnosed with AHB were men, the majority (16) occurred in men who have sex with men. AHB was observed in 4 persons previously unresponsive to vaccination. Regarding antiretroviral treatment (ART), 15 were not receiving ART, two persons were on ART with any HBV active drugs and one person had lamivudine in the regimen. Two persons (11%) developed chronic hepatitis B. There were no cases of fulminant hepatitis. CONCLUSION: The incidence of AHB in HIV positive persons in our cohort was low and shows a progressive decline in the last 20 years. Cases occurred in persons not protected against VHB: not vaccinated or non-responders to vaccine that were not receiving tenofovir.
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The aim of this transversal study was to describe the virological and immunological features of HIV-infected youths transferred from pediatric to adult care units since 1997 vs. the non-transferred patients from the Madrid Cohort of HIV-infected children and adolescents in Spain. We included 106 non-transferred and 184 transferred patients under clinical follow-up in 17 public hospitals in Madrid by the end of December 2017. Virological and immunological outcomes were compared in transferred vs. non-transferred patients. ART drug resistance mutations and HIV-variants were analyzed in all subjects with available resistance pol genotypes and/or genotypic resistance profiles. Among the study cohort, 133 (72.3%) of 184 transferred and 75 (70.7%) of 106 non-transferred patients had available resistance genotypes. Most (88.9%) of transferred had ART experience at sampling. A third (33.3%) had had a triple-class experience. Acquired drug resistance (ADR) prevalence was significantly higher in pretreated transferred than non-transferred patients (71.8% vs. 44%; p = 0.0009), mainly to NRTI (72.8% vs. 31.1%; p < 0.0001) and PI (29.1% vs. 12%; p = 0.0262). HIV-1 non-B variants were less frequent in transferred vs. non-transferred (6.9% vs. 32%; p < 0.0001). In conclusion, the frequent resistant genotypes found in transferred youths justifies the reinforcement of HIV resistance monitoring after the transition to avoid future therapeutic failures.
Asunto(s)
Infecciones por VIH/virología , VIH-1/genética , Adolescente , Adulto , Fármacos Anti-VIH/uso terapéutico , Niño , Preescolar , Estudios de Cohortes , Farmacorresistencia Viral/genética , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , VIH-1/efectos de los fármacos , Humanos , Lactante , Masculino , Mutación/genética , Pediatría , España , Carga Viral/genética , Adulto JovenRESUMEN
BACKGROUND: Linezolid has good penetration to the meninges and could be an alternative for treatment of Staphylococcus aureus meningitis. We assessed the efficacy and safety of linezolid therapy for this infection. METHODS: Retrospective multicenter cohort study of 26 adults treated with linezolid, derived from a cohort of 350 cases of S. aureus meningitis diagnosed at 11 university hospitals in Spain (1981-2015). RESULTS: There were 15 males (58%) and mean age was 47.3 years. Meningitis was postoperative in 21 (81%) patients. The infection was nosocomial in 23 (88%) cases, and caused by methicillin-resistant S. aureus in 15 cases and methicillin-susceptible S. aureus in 11. Linezolid was given as empirical therapy in 10 cases, as directed therapy in 10, and due to failure of vancomycin in 6. Monotherapy was given to 16 (62%) patients. Median duration of linezolid therapy was 17 days (IQR 12-22 days) with a daily dose of 1,200 mg in all cases. The clinical response rate to linezolid was 69% (18/26) and microbiological response was observed in 14 of 15 cases evaluated (93%). Overall 30-day mortality was 23% and was directly associated with infection in most cases. When compared with the patients of the cohort, no significant difference in mortality was observed between patients receiving linezolid or vancomycin for therapy of methicillin-resistant S. aureus meningitis (9% vs. 20%; p = .16) nor between patients receiving linezolid or cloxacillin for therapy of methicillin-susceptible S. aureus meningitis (20% vs 14%; p = .68). Adverse events appeared in 14% (3/22) of patients, but linezolid was discontinued in only one patient. CONCLUSIONS: Linezolid appears to be effective and safe for therapy of S. aureus meningitis. Our findings showed that linezolid may be considered an adequate alternative to other antimicrobials in meningitis caused by S. aureus.
Asunto(s)
Infección Hospitalaria , Linezolid/uso terapéutico , Meningitis Bacterianas/tratamiento farmacológico , Infecciones Estafilocócicas , Adulto , Antibacterianos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina , Persona de Mediana Edad , Estudios Retrospectivos , España , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureusRESUMEN
Background: Integration of human immunodeficiency virus type 1 (HIV-1) into the host genome causes global disruption of the chromatin environment. The abundance level of various chromatin-modifying enzymes produces these alterations and affects both the provirus and cellular gene expression. Here, we investigated potential changes in enzyme expression and global DNA methylation in chronically infected individuals with HIV-1 and compared these changes with non-HIV infected individuals. We also evaluated the effect of viral replication and degree of disease progression over these changes. Results: Individuals with HIV-1 had a significant surge in the expression of DNA and histone methyltransferases (DNMT3A and DNMT3B, SETDB1, SUV39H1) compared with non-infected individuals, with the exception of PRMT6, which was downregulated. Some histone deacetylases (HDAC2 and HDAC3) were also upregulated in patients with HIV. Among individuals with HIV-1 with various degrees of progression and HIV control, the group of treated patients with undetectable viremia showed greater differences with the other two groups (untreated HIV-1 controllers and non-controllers). These latter two groups exhibited a similar behavior between them. Of interest, the overexpression of genes that associate with viral protein Tat (such as SETDB1 along with DNMT3A and HDAC1, and SIRT-1) was more prevalent in treated patients. We also observed elevated levels of global DNA methylation in individuals with HIV-1 in an inverse correlation with the CD4/CD8 ratio. Conclusions: The current study shows an increase in chromatin-modifying enzymes and remodelers and in global DNA methylation in patients with chronic HIV-1 infection, modulated by various levels of viral control and progression.