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1.
PLoS Pathog ; 15(8): e1007991, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31425551

RESUMO

Latency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of the latent reservoir in antiretroviral treated patients. The capacity of the LRAs to perturb the viral reservoir present in distinct subpopulations of cells is currently unknown. Here, using a new RNA FISH/flow ex vivo viral reactivation assay, we performed a comprehensive assessment of the viral reactivation capacity of different families of LRAs, and their combinations, in different CD4+ T cell subsets. We observed that a median of 16.28% of the whole HIV-reservoir induced HIV-1 transcripts after viral reactivation, but only 10.10% of these HIV-1 RNA+ cells produced the viral protein p24. Moreover, none of the LRAs were powerful enough to reactivate HIV-1 transcription in all CD4+ T cell subpopulations. For instance, the combination of Romidepsin and Ingenol was identified as the best combination of drugs at increasing the proportion of HIV-1 RNA+ cells, in most, but not all, CD4+ T cell subsets. Importantly, memory stem cells were identified as highly resistant to HIV-1 reactivation, and only the combination of Panobinostat and Bryostatin-1 significantly increased the number of cells transcribing HIV within this subset. Overall, our results validate the use of the RNA FISH/flow technique to assess the potency of LRAs among different CD4+ T cell subsets, manifest the intrinsic differences between cells that encompass the latent HIV reservoir, and highlight the difficulty to significantly impact the latent infection with the currently available drugs. Thus, our results have important implications for the rational design of therapies aimed at reversing HIV latency from diverse cellular reservoirs.

2.
Nat Commun ; 10(1): 3705, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420544

RESUMO

The identification of exclusive markers to target HIV-reservoir cells will represent a significant advance in the search for therapies to cure HIV. Here, we identify the B lymphocyte antigen CD20 as a marker for HIV-infected cells in vitro and in vivo. The CD20 molecule is dimly expressed in a subpopulation of CD4-positive (CD4+) T lymphocytes from blood, with high levels of cell activation and heterogeneous memory phenotypes. In lymph node samples from infected patients, CD20 is present in productively HIV-infected cells, and ex vivo viral infection selectively upregulates the expression of CD20 during early infection. In samples from patients on antiretroviral therapy (ART) this subpopulation is significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induces cell killing, which reduces the pool of HIV-expressing cells when combined with latency reversal agents. We provide a tool for targeting this active HIV-reservoir after viral reactivation in patients while on ART.

3.
Pharmacotherapy ; 39(4): 501-507, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30723941

RESUMO

STUDY OBJECTIVE: Dual therapy with once/day dolutegravir (DTG) plus boosted darunavir (DRV/b) may be a suitable and effective strategy with a high genetic barrier to resistance in patients infected with human immunodeficiency virus (HIV). Our aim was to evaluate the effectiveness of DTG plus DRV/b (DTG+DRV/b) as a switch strategy in HIV-infected patients, irrespective of their history of virologic failure (VF). DESIGN: Multicenter retrospective cohort study. SETTING: Human immunodeficiency outpatient treatment clinics at three university hospitals in Spain. PATIENTS: Fifty HIV-infected adults who had a stable antiretroviral treatment (ART) regimen and an undetectable viral load for at least 6 months, and whose ART was switched to once/day DTG+DRV/b between January 2015 and January 2018 were included in the analysis. Historical genotype at the time of VF was available in 44 patients. MEASUREMENTS AND MAIN RESULTS: Patients were followed until VF or treatment discontinuation for any reason. The primary outcome was the percentage of patients with a viral load of 50 copies/mL or lower at the last follow-up visit. Secondary outcomes included changes in CD4+ cell count, lipid profile, and renal function. Of the 50 patients included, median time of viral suppression was 52 months (interquartile range [IQR] 18-103 mo) and nadir CD4+ 89 cells/mm3 (IQR 37-241 cells/mm3 ). Patients had a history of a median of 8 ART combinations (IQR 4-11 combinations) and 3 VFs (IQR 2-8 VFs). The historical genotypes from 44 patients showed 41 patients (93.2%) with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs), 32 (72.7%) with nonnucleoside reverse transcriptase inhibitor (NNRTI) RAMs, and 12 (27.3%) with primary protease inhibitor (PI) RAMs; 7 (15.9%) had darunavir RAMs, and no patients had baseline integrase strand transfer inhibitor RAMs. Thirty-seven patients (84.1%) had resistance to at least two antiretroviral classes. After a median of 25 months (IQR 17-28 mo) of follow-up, 49 patients (98%) maintained a viral load of 50 copies/mL or lower, and 1 patient (2%) had VF. No new RAMs emerged at VF. At week 4, serum creatinine concentration increased a median of 0.12 mg/dl (0.03-0.23 mg/dl). At last visit, total cholesterol and low-density lipoprotein cholesterol levels increased by a median of 9 mg/dl (IQR -18 to 40 mg/dl) and 16 mg/dl (IQR -9 to 40 mg/dl), respectively, whereas CD4+ cell count remained stable (median +13 cell/mm3 ). CONCLUSION: In this cohort of heavily treated HIV-infected patients with virologic suppression, switching to the combination of DTG+DRV/b was a convenient regimen that was highly effective and had good tolerability.

4.
AIDS Rev ; 20(4): 179-186, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30548024

RESUMO

Advances in antiretroviral therapy have led to dramatic improvements in survival of HIV-infected persons. However, HIV cure remains elusive and lifelong treatment is needed. Attempts for reducing long-term drug exposure, toxicities, and cost, while maintaining viral suppression, have led to explore whether maintenance strategies with less than triple therapy could be feasible using the newest more potent antiretrovirals. While monotherapies have failed to do so with selection of drug resistance, some dual combinations have proven its efficacy when used sequentially in patients with viral suppression under standard triple regimens. Furthermore, the advent of coformulations makes easier long-term drug adherence. Herein, we review the current experience with the new single tablet regimen of dolutegravir (DTG) and rilpivirine (RPV) (Juluca®). It is the first approved two-drug single-tablet regimen and the first dual nuc-sparing coformulation. Two randomized, non-inferiority clinical trials (SWORD-1 and -2) and five observational studies have evaluated DTG-RPV in treatment-experienced patients. Despite distinct inclusion criteria, more than 95% of patients kept plasma HIV-RNA undetectable for at least 48 weeks. Along with virological efficacy being non-inferior to triple regimens, the tolerance of DTG-RPV was good, being discontinuations due to adverse events only 0.8-7.9%. Moreover, improvements were seen in lipid profiles in patients switched from protease inhibitors, and in renal and bone biomarkers in those switched from tenofovir disoproxil fumarate. Finally, resistance is rare failing on DTG-RPV. In summary, DTG-RPV is a novel two-drug coformulation that can be effectively and safely used in treatment-experienced patients with viral suppression if the virus is fully susceptible to both drugs. Its unique features make this drug one of the best options as long-term regimen or lifelong maintenance HIV therapy.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Substituição de Medicamentos/métodos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Quimioterapia de Manutenção/métodos , Rilpivirina/administração & dosagem , Combinação de Medicamentos , Farmacorresistência Viral , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resposta Viral Sustentada , Resultado do Tratamento
5.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 36(3): 157-164, mar. 2018. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-171410

RESUMO

Introducción: El objetivo de este estudio es estimar el impacto económico en España de la optimización del tratamiento antirretroviral (TAR) triple en pacientes con carga viral suprimida según las recomendaciones GeSIDA/PNS (2015) y su aplicabilidad en la práctica clínica. Métodos: A partir de los datos de prescripción del TAR de la encuesta hospitalaria 2014, siguiendo las recomendaciones de GeSIDA/PNS de optimización de TAR con grado de evidencia A-I, se desarrolló un modelo farmacoeconómico. Las pautas de optimización, la voluntad de optimización y demás asunciones y resultados del modelo fueron validados por un panel de expertos en la infección por VIH (infectológos y farmacéuticos hospitalarios). El análisis se realizó desde la perspectiva del SNS, considerando el coste farmacológico anual, precio de venta del laboratorio notificado, deducción RD-Ley-8/2010 e IVA. Resultados: El panel seleccionó 6 estrategias de optimización y estimó que en España de los 80.859 pacientes actualmente en TAR triple, 10.863 (13,4%) serían candidatos a optimizar su TAR según estas estrategias, generando ahorros de 15,9M euros /año (2,4% del coste farmacológico del TAR triple). Las estrategias más factibles (>40% del total de pacientes candidatos a optimizar, n=4.556) y asociadas a mayores reducciones del gasto (ahorro entre 653 y 4.797 euros /paciente-año según el TAR triple de partida) serían las optimizaciones a ATV/r+3TC. Conclusión: La aplicación a la práctica clínica española de las principales estrategias de optimización recomendadas en el documento GeSIDA/PNS (2015) generaría ahorros sustanciales, especialmente aquellas basadas en biterapia con ATV+3TC, contribuyendo así al control del gasto farmacéutico y a la sostenibilidad del SNS (AU)


Introduction: The objective of this study is to estimate the economic impact associated with the optimisation of triple antiretroviral treatment (ART) in patients with undetectable viral load according to the recommendations from the GeSIDA/PNS (2015) Consensus and their applicability in the Spanish clinical practice. Methods: A pharmacoeconomic model was developed based on data from a National Hospital Prescription Survey on ART (2014) and the A-I evidence recommendations for the optimisation of ART from the GeSIDA/PNS (2015) consensus. The optimisation model took into account the willingness to optimise a particular regimen and other assumptions, and the results were validated by an expert panel in HIV infection (Infectious Disease Specialists and Hospital Pharmacists). The analysis was conducted from the NHS perspective, considering the annual wholesale price and accounting for deductions stated in the RD-Law 8/2010 and the VAT. Results: The expert panel selected six optimisation strategies, and estimated that 10,863 (13.4%) of the 80,859 patients in Spain currently on triple ART, would be candidates to optimise their ART, leading to savings of 15.9M euros /year (2.4% of total triple ART drug cost). The most feasible strategies (>40% of patients candidates for optimisation, n=4,556) would be optimisations to ATV/r+3TC therapy. These would produce savings between 653 euros and 4,797 euros per patient per year depending on baseline triple ART. Conclusion: Implementation of the main optimisation strategies recommended in the GeSIDA/PNS (2015) Consensus into Spanish clinical practice would lead to considerable savings, especially those based in dual therapy with ATV/r+3TC, thus contributing to the control of pharmaceutical expenditure and NHS sustainability (AU)


Assuntos
Humanos , Masculino , Feminino , Antirretrovirais/uso terapêutico , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Consenso , Síndrome de Imunodeficiência Adquirida/economia , Gastos em Saúde/tendências , Impactos na Saúde/economia , Otimização/economia , Farmacoeconomia/organização & administração
6.
AIDS Rev ; 20(1): 3-13, 2018 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29369304

RESUMO

Advanced HIV disease, defined as a CD4 cell count below 200 cells/µl or the presence of an AIDS-defining illness, remains common among HIV-infected individuals who first present for medical care. In developed countries, nearly 30% of new HIV diagnoses occurred at advanced stages of the disease, and it is important because advanced HIV disease has been associated with worse clinical outcomes, including lower rates of virological response, higher morbidity, and higher mortality. However, there are scarce data regarding which is the best antiretroviral regimen in these patients. Nowadays, integrase inhibitor-based regimens are widely recommended as the best initial therapy for treatment-naïve HIV-infected patients by all international guidelines. However, these guidelines hardly mention the recommended regimens in individuals with advanced HIV disease. Otherwise, recent data indicating a higher risk of immune reconstitution inflammatory syndrome associated to the use of integrase inhibitors have raised concerns on the use of these drugs in patients with advanced HIV disease. The aim of this article is to review the available evidence from randomized clinical trials for the best treatment in patients with advanced HIV disease.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Feminino , Infecções por HIV/complicações , Infecções por HIV/imunologia , Humanos , Síndrome Inflamatória da Reconstituição Imune/etiologia , Síndrome Inflamatória da Reconstituição Imune/prevenção & controle , Masculino
7.
Enferm Infecc Microbiol Clin ; 36(3): 157-164, 2018 03.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28109551

RESUMO

INTRODUCTION: The objective of this study is to estimate the economic impact associated with the optimisation of triple antiretroviral treatment (ART) in patients with undetectable viral load according to the recommendations from the GeSIDA/PNS (2015) Consensus and their applicability in the Spanish clinical practice. METHODS: A pharmacoeconomic model was developed based on data from a National Hospital Prescription Survey on ART (2014) and the A-I evidence recommendations for the optimisation of ART from the GeSIDA/PNS (2015) consensus. The optimisation model took into account the willingness to optimise a particular regimen and other assumptions, and the results were validated by an expert panel in HIV infection (Infectious Disease Specialists and Hospital Pharmacists). The analysis was conducted from the NHS perspective, considering the annual wholesale price and accounting for deductions stated in the RD-Law 8/2010 and the VAT. RESULTS: The expert panel selected six optimisation strategies, and estimated that 10,863 (13.4%) of the 80,859 patients in Spain currently on triple ART, would be candidates to optimise their ART, leading to savings of €15.9M/year (2.4% of total triple ART drug cost). The most feasible strategies (>40% of patients candidates for optimisation, n=4,556) would be optimisations to ATV/r+3TC therapy. These would produce savings between €653 and €4,797 per patient per year depending on baseline triple ART. CONCLUSION: Implementation of the main optimisation strategies recommended in the GeSIDA/PNS (2015) Consensus into Spanish clinical practice would lead to considerable savings, especially those based in dual therapy with ATV/r+3TC, thus contributing to the control of pharmaceutical expenditure and NHS sustainability.

8.
Artigo em Inglês | MEDLINE | ID: mdl-29237008

RESUMO

Objectives: To determine the effect of etravirine on the pharmacokinetics of darunavir/cobicistat and vice versa. Safety and tolerability of this combination were also evaluated. Methods: Open-label, fixed-sequence trial in two cohorts of HIV-infected patients on therapy with darunavir/cobicistat 800/150 mg once daily (DRV cohort; n = 15) or etravirine 400 mg once daily (ETR cohort; n = 15). Etravirine or darunavir/cobicistat were added on days 1-14 and 1-7 in participants in the DRV or ETR cohort, respectively. Full pharmacokinetic profiles were obtained on days 0 and 14 in the DRV cohort, and on days 0 and 7 in the ETR cohort. Darunavir, cobicistat and etravirine pharmacokinetic parameters [AUC0-24, Cmax and trough concentrations in plasma (C24)] were calculated for each individual by non-compartmental analysis and were compared using linear mixed-effects models. Adverse events and HIV-1 RNA in plasma were monitored. Results: Etravirine co-administration decreased cobicistat AUC0-24, Cmax and C24 by 30%, 14% and 66%, respectively. Although darunavir AUC0-24 and Cmax were unchanged by etravirine, darunavir C24 was 56% lower for darunavir/cobicistat co-administered with etravirine relative to darunavir/cobicistat alone. Etravirine pharmacokinetics were unchanged by darunavir/cobicistat. Treatments were well tolerated, and HIV-1 RNA remained undetectable in all participants. Conclusions: Although etravirine pharmacokinetics was unchanged by darunavir/cobicistat, there was a significant decrease in cobicistat exposure and in darunavir C24 when darunavir/cobicistat was co-administered with etravirine. Boosting darunavir with ritonavir instead of with cobicistat may be preferred if darunavir is to be combined with etravirine in clinical practice.

9.
Clin Infect Dis ; 65(12): 2112-2118, 2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-29020293

RESUMO

Background: Our objective was to assess the therapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for maintenance of human immunodeficiency virus type 1 (HIV-1) suppression. Methods: This was a multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1 RNA <50 copies/mL for 6 months or longer on triple therapy with darunavir/ritonavir and 2 nucleos(t)ides (tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine) and with no resistance were randomized to continue therapy (n = 128) or switch to darunavir/ritonavir and lamivudine (n = 129). The primary endpoint was the proportion of participants with HIV-RNA <50 copies/mL after 48 weeks of follow-up according to the snapshot algorithm. Results: A total of 249 participants received study drugs (intention-to-treat exposed). The proportion of participants with HIV-RNA <50 copies/mL in the dual- and triple-therapy arms was 88.9% (112/126) and 92.7% (114/123; difference, -3.8%; 95% confidence interval, -11.0 to 3.4), respectively. Four participants in the dual-therapy arm and 2 in the triple-therapy arm developed protocol-defined virological failure. Switching to dual therapy was associated with a significant increase in total, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol, but not in the total-to-HDL cholesterol ratio. Serious adverse events and study drug discontinuations due to adverse events occurred in 4.8% vs 4.9%P = .97) and in 0.8% (1/126) vs 1.6% P = .55) in dual therapy vs triple therapy, respectively. Conclusions: Dual therapy with darunavir/ritonavir and lamivudine demonstrated noninferior therapeutic efficacy and similar tolerability compared to triple therapy. Clinical Trials Registration: NCT02159599.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Carga Viral/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Darunavir/administração & dosagem , Darunavir/uso terapêutico , Didesoxinucleosídeos/administração & dosagem , Didesoxinucleosídeos/uso terapêutico , Emtricitabina/administração & dosagem , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , Humanos , Lamivudina/administração & dosagem , Lamivudina/uso terapêutico , Masculino , Conduta do Tratamento Medicamentoso , Pessoa de Meia-Idade , RNA Viral/sangue , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Tenofovir/administração & dosagem , Tenofovir/uso terapêutico
10.
MBio ; 8(4)2017 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-28698276

RESUMO

Cells that actively transcribe HIV-1 have been defined as the "active viral reservoir" in HIV-infected individuals. However, important technical limitations have precluded the characterization of this specific viral reservoir during both treated and untreated HIV-1 infections. Here, we used a novel single-cell RNA fluorescence in situ hybridization-flow cytometry (FISH-flow) assay that requires only 15 million unfractionated peripheral blood mononuclear cells (PBMCs) to characterize the specific cell subpopulations that transcribe HIV RNA in different subsets of CD4+ T cells. In samples from treated and untreated HIV-infected patients, effector memory CD4+ T cells were the main cell population supporting HIV RNA transcription. The number of cells expressing HIV correlated with the plasma viral load, intracellular HIV RNA, and proviral DNA quantified by conventional methods and inversely correlated with the CD4+ T cell count and the CD4/CD8 ratio. We also found that after ex vivo infection of unstimulated PBMCs, HIV-infected T cells upregulated the expression of CD32. In addition, this new methodology detected increased numbers of primary cells expressing viral transcripts and proteins after ex vivo viral reactivation with latency reversal agents. This RNA FISH-flow technique allows the identification of the specific cell subpopulations that support viral transcription in HIV-1-infected individuals and has the potential to provide important information on the mechanisms of viral pathogenesis, HIV persistence, and viral reactivation.IMPORTANCE Persons infected with HIV-1 contain several cellular viral reservoirs that preclude the complete eradication of the viral infection. Using a novel methodology, we identified effector memory CD4+ T cells, immune cells preferentially located in inflamed tissues with potent activity against pathogens, as the main cells encompassing the transcriptionally active HIV-1 reservoir in patients on antiretroviral therapy. Importantly, the identification of such cells provides us with an important target for new therapies designed to target the hidden virus and thus to eliminate the virus from the human body. In addition, because of its ability to identify cells forming part of the viral reservoir, the assay used in this study represents an important new tool in the field of HIV pathogenesis and viral persistence.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Citometria de Fluxo/métodos , Infecções por HIV/virologia , HIV-1/genética , Hibridização in Situ Fluorescente/métodos , Transcrição Genética , Adulto , Linfócitos T CD4-Positivos/ultraestrutura , Infecções por HIV/imunologia , HIV-1/imunologia , HIV-1/fisiologia , Humanos , Memória Imunológica , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/virologia , Pessoa de Meia-Idade , RNA Viral/genética , Receptores de IgG/genética , Análise de Célula Única , Carga Viral , Latência Viral
11.
Transfusion ; 57(9): 2164-2173, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28681400

RESUMO

BACKGROUND: Human immunodeficiency virus 1 (HIV-1) subtype B is predominant in Spain. However, the recent arrival of immigrant populations has increased the prevalence of non-B subtypes and circulating recombinant forms. The objective of this study was to determine the prevalence of HIV-1 subtypes and transmitted drug-resistance mutations in blood donors from the Catalonian region (northeastern Spain). STUDY DESIGN AND METHODS: HIV-1-positive blood donors identified in Catalonia from 2005 to 2014 were included. Demographic variables and risk factors for HIV-1 acquisition were recorded. HIV-1 subtyping was carried out by HIV-1 DNA polymerase region sequencing, and phylogenetic analyses were performed using the neighbor-joining method. RESULTS: During the study period, 2.8 million blood donations were screened, and 214 HIV-1-positive donors were identified, yielding an overall prevalence of 7.7 per 100,000 donations (89% men; mean age, 34 ± 10 years). Most HIV-1-positive donors were native to Spain (81%), and 61% were regular blood donors. When risk factors were known, 62% reportedly were men who had sex with men. HIV-1 subtyping was possible in 176 HIV-1-positive individuals: 143 (81%) had HIV-1 subtype B, and 33 (19%) had non-B subtypes. Most HIV-1 non-B subtypes were circulating recombinant forms (n = 20; 61%). Factors associated with HIV-1 subtype B were male sex (p = 0.007) and men who had sex with men (p < 0.001). The overall prevalence of transmitted drug-resistance mutations was 14%. CONCLUSION: Non-B subtypes, circulating recombinant forms, and transmitted drug-resistance mutation sequences circulate among HIV-1-positive blood donors in Catalonia. Continuous local epidemiological surveillance is required to implement optimal prevention strategies for controlling transfusion-transmitted HIV and to improve health policies regarding HIV infection.


Assuntos
Doadores de Sangue/provisão & distribução , Infecções por HIV/epidemiologia , HIV-1/genética , Adulto , Farmacorresistência Viral , Emigração e Imigração , Infecções por HIV/transmissão , Humanos , Mutação , Filogenia , Prevalência , Análise de Sequência de DNA , Espanha/epidemiologia , Adulto Jovem
13.
HIV Clin Trials ; 18(2): 49-53, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28081673

RESUMO

BACKGROUND: The objective of this study was to determine the impact of tenofovir or abacavir discontinuation on low-density lipoprotein (LDL) phenotype and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in HIV-infected patients treated with lopinavir/ritonavir plus 2 nucleos(t)ide reverse transcriptase inhibitors (NRTI). METHODS: Multicenter, open-label study. Patients were randomized to continue with lopinavir/ritonavir plus 2 NRTI (triple therapy) or to switch to lopinavir/ritonavir plus lamivudine (dual therapy). LDL phenotype (by gradient gel electrophoresis) and Lp-PLA2 (by 2-thio-PAF) were determined at baseline and week 48. RESULTS: Forty-four patients included (triple therapy n = 19, dual therapy n = 25): men 63.6%, age 41.5 years (25-61), Framingham score 4.9% (0.2-22). Tenofovir was part of the regimen in 28 (63.6%) patients. Dual therapy patients were younger (p = 0.013) and had lower baseline apolipoprotein A1 (p = 0.029). At week 48, there were no changes in standard lipid measurements, except ApoA1/Apo B, which increased in dual therapy (p = 0.038) with no differences between arms. At week 48, no change in LDL phenotype was found in either arm. No changes in total Lp-PLA2 activity or the relative distribution of LDL and HDL particles were found at week 48 in either arm. CONCLUSIONS: Discontinuing the third nucleos(t)ide, mainly tenofovir and abacavir, in a lopinavir/ritonavir-containing regimen was not associated with a deleterious effect on LDL phenotype nor in Lp-PLA2 activity.


Assuntos
Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/metabolismo , Lamivudina/efeitos adversos , Lipoproteínas LDL/metabolismo , Lopinavir/efeitos adversos , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , 1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo , Fármacos Anti-HIV , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Biomarcadores , Contagem de Linfócito CD4 , Didesoxinucleosídeos/administração & dosagem , Combinação de Medicamentos , Substituição de Medicamentos , Feminino , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Lamivudina/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Lipoproteínas LDL/sangue , Lopinavir/administração & dosagem , Masculino , Carga Viral
14.
Antivir Ther ; 22(1): 89-90, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27546463

RESUMO

An HIV-infected patient treated with tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat developed severe acute ischaemia of both legs during a migraine episode. After being interrogated he admitted taking an ergotamine-containing preparation. Ergotism due to interaction between ergotics and cobicistat was diagnosed. We describe the first reported case of this interaction.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Cobicistat/efeitos adversos , Ergotamina/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Isquemia/etiologia , Doença Aguda , Adulto , Fármacos Anti-HIV/administração & dosagem , Cobicistat/administração & dosagem , Interações de Medicamentos , Quimioterapia Combinada , Ergotamina/administração & dosagem , Humanos , Perna (Membro) , Masculino , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/tratamento farmacológico
15.
PLoS One ; 11(10): e0164455, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27727331

RESUMO

OBJECTIVES: Based on data from clinical practice, we evaluated the effectiveness and safety of switching to abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV) treatment in virologically suppressed HIV-1-infected patients. METHODS: We performed a multicenter, non-controlled, retrospective study of HIV-1-infected patients who switched treatment to ABC/3TC+RPV. Patients had an HIV-RNA <50 copies/mL for at least 24 weeks prior to changing treatments. The primary objective was HIV-1 RNA <50 copies/mL at week 48. Effectiveness was analyzed by intention-to-treat (ITT), missing = failure and on-treatment (OT) analyses. The secondary objectives analyzed were adverse effects changes in renal, hepatic or lipid profiles, changes in CD4+ cell count and treatment discontinuations. RESULTS: Of the 205 patients included, 75.6% were men and the median age was 49. At baseline, before switching to ABC/3TC+RPV, median time since HIV diagnosis was 13.1 years, median time with undetectable HIV-1 RNA was 6.2 years and median time of previous antiretroviral regimen was 3.1 years (48.3% patients were taking efavirenz and ABC/3TC was the most frequent backbone coformulation in 69.7% of patients). The main reasons for switching were drug toxicity/poor tolerability (60.5%) and simplification (20%). At week 48, the primary objective was achieved by 187 out of 205 (91.2%) patients by ITT analysis, and 187 out of 192 (97.4%) patients by OT analysis. The CD4+ lymphocyte count and CD4+ percentage increased significantly from baseline to week 48 by a median of 48 cells/µL (-50 to 189) and 1.2% (-1.3% to 4.1%), respectively, P<0.001. Thirty-eight adverse events (AE) were detected in 32 patients. Of these, 25 had no clear association with treatment. Three patients interrupted therapy due to AE. We observed a decrease in all lipid parameters, P<0.001, and a slight improvement in the glomerular filtration rate, P<0.01. Therapy was considered to have failed in 18 patients owing to virological failure (5 [2.4%]), toxicity/poor tolerability (4 [2%]), clinical decision (3 [1.5%]), loss to follow-up (3 [1.5%]), death (1 [0.5%]), and no clinical data (2 [1%]). CONCLUSIONS: The results of this study confirms that ABC/3TC+RPV is an effective, safe, and cost-effective option for the treatment of patients with virologically stable HIV-1 infection.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Rilpivirina/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Depressão/etiologia , Didesoxinucleosídeos/efeitos adversos , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Rim/metabolismo , Lamivudina/efeitos adversos , Lipídeos/sangue , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Retrospectivos , Rilpivirina/efeitos adversos , Resultado do Tratamento
16.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 34(8): 516.e1-516.e18, oct. 2016. tab
Artigo em Inglês | IBECS | ID: ibc-156256

RESUMO

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 (AU)


A pesar del gran avance que ha supuesto el tratamiento antirretroviral (TAR) para el pronóstico de la infección por el VIH, las infecciones oportunistas (IO) continúan siendo causa de morbilidad y mortalidad en estos pacientes. Ello ocurre en muchos casos debido a la inmunodepresión grave, bien ante la falta de adherencia al TAR, el fracaso del mismo o el desconocimiento de la existencia de la infección por el VIH en pacientes que comienzan con una IO. El presente artículo actualiza las recomendaciones de prevención y tratamiento de diferentes infecciones en pacientes con infección por VIH: parasitarias, fúngicas, víricas, micobacterianas, bacterianas e importadas, además del síndrome de reconstitución inmune (AU)


Assuntos
Humanos , Infecções por HIV/complicações , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antirretrovirais/uso terapêutico , Avaliação de Resultado de Ações Preventivas , Coinfecção/epidemiologia , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Padrões de Prática Médica
17.
Artigo em Espanhol | IBECS | ID: ibc-156257

RESUMO

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 (AU)


Las infecciones oportunistas siguen siendo una causa importante de morbi mortalidad en pacientes con infección por VIH. Ello ocurre en muchos casos debido a la inmunodepresión grave, bien ante la falta de adherencia al tratamiento antirretroviral, el fracaso del mismo o el desconocimiento de la existencia de la infección por el VIH en pacientes que comienzan con una infección oportunista. Este artículo es un resumen del documento de consenso que actualiza las recomendaciones previas de GESIDA respecto a la prevención y el tratamiento de las diferentes infecciones oportunistas en pacientes infectados por VIH: parasitarias, fúngicas, víricas, micobacterianas, bacterianas e importadas, además del síndrome de reconstitución inmune. Está dirigido a los profesionales que trabajan en la práctica clínica en el campo del VIH, con el objetivo de facilitarles una atención de calidad en la prevención y tratamiento de estas infecciones (AU)


Assuntos
Humanos , Infecções por HIV/complicações , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antirretrovirais/uso terapêutico , Coinfecção/epidemiologia , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Padrões de Prática Médica
18.
J Antimicrob Chemother ; 71(12): 3510-3514, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27591292

RESUMO

OBJECTIVES: To describe the effectiveness and safety of an abacavir/lamivudine + rilpivirine regimen in naive HIV-1-infected patients, as there is a lack of data with this combination. METHODS: This was an observational, retrospective, multicentre study in eight Spanish hospitals. All antiretroviral-naive patients ≥18 years old and starting abacavir/lamivudine + rilpivirine were included. Effectiveness (ITT and on-treatment) and safety (adverse events and laboratory parameters) were assessed during follow-up. Values are expressed as n (%) or median (IQR). The Wilcoxon signed-rank test was used to compare baseline and 6 and 12 month values. RESULTS: Eighty-four patients were included [93% males, age = 36 (30-45) years]. Time since HIV diagnosis was 12 (4-35) months. Fifty-one per cent of patients had comorbidities. Baseline CD4+ was 425 (340-519) cells/mm3 and baseline HIV-RNA was 19 000 (9500-42 000) copies/mL. Median follow-up was 18 (9-22) months; 100% and 68% patients with at least 6 and 12 months, respectively. At 6 and 12 months effectiveness was 94% and 86% by ITT analysis and 96% and 97% by on-treatment analysis. At 12 months, there were significant increases in CD4+ (+262 cell/mm3) and HDL cholesterol (+4 mg/dL) and a significant decrease in the total cholesterol/HDL cholesterol ratio (-0.2). There were two (2.4%) virological failures (HIV-RNA 50-100 copies/mL); one patient later achieving virological suppression without changing the treatment. Six patients (7.1%) changed treatment due to reasons other than virological failure or side effects. One patient discontinued treatment due to gastrointestinal complaints attributed to abacavir/lamivudine. CONCLUSIONS: Abacavir/lamivudine + rilpivirine was an effective and safe option in a selected group of HIV-1-infected treatment-naive patients.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/administração & dosagem , Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/tratamento farmacológico , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Rilpivirina/administração & dosagem , Rilpivirina/efeitos adversos , Adulto , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , HIV-1/efeitos dos fármacos , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Resultado do Tratamento
19.
Enferm Infecc Microbiol Clin ; 34(8): 517-23, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27056581

RESUMO

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.


Assuntos
Infecções por HIV/complicações , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controle , Coinfecção/tratamento farmacológico , Coinfecção/prevenção & controle , Humanos , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/prevenção & controle , Micoses/tratamento farmacológico , Micoses/prevenção & controle , Doenças Parasitárias/tratamento farmacológico , Doenças Parasitárias/prevenção & controle , Viroses/tratamento farmacológico , Viroses/prevenção & controle
20.
Enferm Infecc Microbiol Clin ; 34(8): 516.e1-516.e18, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26976381

RESUMO

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.


Assuntos
Infecções por HIV/complicações , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Terapia Antirretroviral de Alta Atividade , Infecções Bacterianas/tratamento farmacológico , Coinfecção , Humanos , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/prevenção & controle , Infecções por Mycobacterium/tratamento farmacológico , Infecções por Mycobacterium/prevenção & controle , Micoses/tratamento farmacológico , Micoses/prevenção & controle , Infecções Oportunistas/etiologia , Doenças Parasitárias/tratamento farmacológico , Doenças Parasitárias/prevenção & controle , Viroses/tratamento farmacológico , Viroses/prevenção & controle
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