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1.
BMC Infect Dis ; 19(1): 883, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646969

RESUMO

BACKGROUND: Penicillin G Benzathine (PGB) is the cornerstone of syphilis treatment. However, its intramuscular (IM) administration is associated with pain at the site of injection. The dilution of PGB with local anesthetics is recommended in some guidelines, but the evidence that supports it, particularly in adults and in HIV infection, is scarce. Preliminary clinical experience also suggests that the IM administration of PGB through increased needle gauges might improve its tolerability. The aim of the study to identify less painful ways of administering IM PGB in the treatment of syphilis in adults. METHODS: Multicenter, randomized, double-blinded clinical trial in patients diagnosed with primary syphilis that required a single IM injection of PGB 2400,00 IU. Patients were randomized to receive PGB diluted with 0.5 mL mepivacaine 1% (MV) or PGB alone, and both groups either with a long 19G or short 21G IM needle. The primary objective was the effect on local pain immediately after the administration through a visual scale questionnaire on pain (0 to 10). RESULTS: One hundred eight patients were included, 27 in each group. Ninety-four (94.4%) were male, and 41.7% were also HIV-infected. Mean age 36.6 years (SD 11). Significant differences in immediate pain intensity were observed when comparing the long 19G group with anesthesia (mean pain intensity, [MPI] 2.92 [CI 95% 1.08-4.07]) vs long 19G without anesthesia (MPI 5.56 [CI 95% 4.39-6.73), p < 0.001; and also between short 21G group with anesthesia (MPI 3.36 [CI 95% 2.22-4.50]) vs short 21G without anesthesia (MPI 5.06 [CI 95% 3.93-6.19]), p = 0.015). No significant differences in immediate pain were observed between 19G and 21G in the presence or absence of anesthesia (p = 1.0 in both cases). No differences were found between study arms after 6 and 24 h. CONCLUSIONS: The IM administration of 1% mepivacaine-diluted PGB induces significantly less immediate local pain as compared to PGB alone. The needle gauge did not have any effect on the pain. Based on these results, we suggest anesthetic-diluted IM PGB as the standard treatment for primary syphilis. TRIAL REGISTRATION: EudraCT 2014-003969-24 (Date of registration 18/09/2014).


Assuntos
Anestésicos Locais/uso terapêutico , Mepivacaína/uso terapêutico , Dor/tratamento farmacológico , Penicilina G Benzatina/uso terapêutico , Sífilis/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adolescente , Adulto , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Infecções por HIV/microbiologia , Humanos , Injeções Intramusculares/instrumentação , Masculino , Mepivacaína/administração & dosagem , Mepivacaína/efeitos adversos , Agulhas , Penicilina G Benzatina/administração & dosagem , Penicilina G Benzatina/efeitos adversos
2.
Antiviral Res ; 170: 104577, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31386862

RESUMO

Not all HIV-infected patients receiving cART are able to recover optimal CD4-T cell levels despite achieving undetectable viremia. We evaluated the potential association between polymorphisms (SNPs) in cytokines involved in immune response (IL15, IFNγ and IL19) and the failure to achieve optimal CD4 T-cells restoration after cART. For this, we carried out a retrospective study in 412 HIV-infected patients starting cART with CD4<200 cells/µL. These patients were classified as immunological non-responders (INR) if having a CD4 increase (ΔCD4) below 200 cells/µL after two years on successful cART. IL15, IFNγ and IL19 polymorphisms were genotyped using Sequenom's MassARRAY platform. We found 134 INR patients with a median [IQR] ΔCD4 = 133[73-174] cells/µL. In the multivariate analysis adjusted for age, sex, infection route, ethnic origin, hepatitis co-infection and HIV infection length, the AA genotype of the SNP rs2430561 in IFNγ (OR:2.01[1.13-3.56], p = 0.017) and the TT genotype of polymorphism rs2243191 in IL19 (OR:2.58 [1.17-5.68], p = 0.019) showed significant association with the INR status. Our results show that polymorphisms in IFNγ and IL19 genes significantly impacts in the probability of not achieving an optimal immune recovery in HIV-patients starting cART with CD4 T-cells <200 cells/µL. Thus, these SNPs could represent potential predictive markers of the immunodiscordant response.

3.
Clin Infect Dis ; 69(12): 2229, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31322167
4.
Nutrients ; 11(6)2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31208015

RESUMO

Human immunodeficiency virus (HIV) infection is characterized by an early depletion of the mucosal associated T helper (CD4+) cells that impair the host immunity and impact the oral and gut microbiomes. Although, the HIV-associated gut microbiota was studied in depth, few works addressed the dysbiosis of oral microbiota in HIV infection and, to our knowledge, no studies on intervention with prebiotics were performed. We studied the effect of a six-week-long prebiotic administration on the salivary microbiota in HIV patients and healthy subjects. Also, the co-occurrence of saliva microorganisms in the fecal bacteria community was explored. We assessed salivary and feces microbiota composition using deep 16S ribosomal RNA (rRNA) gene sequencing with Illumina methodology. At baseline, the different groups shared the same most abundant genera, but the HIV status had an impact on the saliva microbiota composition and diversity parameters. After the intervention with prebiotics, we found a drastic decrease in alpha diversity parameters, as well as a change of beta diversity, without a clear directionality toward a healthy microbiota. Interestingly, we found a differential response to the prebiotics, depending on the initial microbiota. On the basis of 100% identity clustering, we detected saliva sequences in the feces datasets, suggesting a drag of microorganisms from the upper to the lower gastrointestinal tract.


Assuntos
Microbioma Gastrointestinal , Infecções por HIV , Prebióticos , Saliva/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Infecções por HIV/dietoterapia , Infecções por HIV/genética , Infecções por HIV/microbiologia , Humanos , RNA Bacteriano/genética
5.
Lancet ; 393(10189): 2428-2438, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31056293

RESUMO

BACKGROUND: The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships. METHODS: The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. FINDINGS: Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1-3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33-46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4-2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up). INTERPRETATION: Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV. FUNDING: National Institute for Health Research.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Soropositividade para HIV/transmissão , Homossexualidade Masculina , Sexo sem Proteção , Adulto , Terapia Antirretroviral de Alta Atividade , Preservativos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Parceiros Sexuais , Carga Viral
6.
Nefrologia ; 39(5): 497-505, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31027896

RESUMO

BACKGROUND: The use of combination antiretroviral therapy has led to dramatic improvements in the life expectancy of HIV-infected persons. As result, the HIV population is aging and increasingly facing illnesses typically seen in the elderly, such as chronic kidney disease (CKD). METHODS: A retrospective longitudinal study was conducted using data from years 2010 and 2014 in all HIV-infected persons enrolled at the Spanish VACH cohort. We analyzed the prevalence and the predictive factors for developing CKD (estimated glomerular filtration rate, eGFR<60mL/min/1.73m2). RESULTS: The CKD prevalence at baseline was 456/8968, 5.1% [4.6-5.6%]. Of 8512 HIV-positive individuals examined without CKD at baseline (73.7% male, median age 44 years-old), 2.15% developed CKD (eGFR<60mL/min/1.73m2). The odds ratios [95%CI] for the independent predictive factors identified were gender (male) 0.54 [0.39-0.75], age (per year) 1.08 [1.07-1.10], AIDS diagnosis 1.40 [1.03-1.91], protease inhibitor-based regimens 1.49 [1.10-2.02], hypertension 1.37 [0.94-1.99], diabetes 1.84 [1.33-2.55] and history of cardiovascular events 1.66 [0.96-2.86]. CONCLUSION: The prevalence and risk factors for CKD and its progression are high in the VACH cohort. Thus, preventive measures such as control of hypertension, diabetes and obesity, as well as efforts for avoiding exposure to nephrotoxic drugs, including some antiretrovirals, are warranted in this aging HIV population.

7.
Clin Infect Dis ; 68(1): 120-130, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29788075

RESUMO

Background: While nutritional interventions with prebiotics and probiotics seem to exert immunological effects, their clinical implications in human immunodeficiency virus (HIV)-infected subjects initiating antiretroviral therapy (ART) at advanced HIV disease remain unclear. Methods: This was a pilot multicenter randomized, placebo-controlled, double-blind study in which 78 HIV-infected, ART-naive subjects with <350 CD4 T cells/µL or AIDS were randomized to either daily PMT25341 (a mixture of synbiotics, omega-3/6 fatty acids and amino acids) or placebo for 48 weeks, each in combination with first-line ART. Primary endpoints were changes in CD4 T-cell counts and CD4/CD8 ratio from baseline to week 48 and safety. Secondary endpoints were changes in markers of T-cell activation, bacterial translocation, inflammation, and α and ß microbiota diversity. Results: Fifty-nine participants completed the follow-up with a mean CD4+ T-cell count of 221 ± 108 cells/µL and mean CD4/CD8 ratio of 0.26 ± 0.19. PMT25341 was well tolerated, without grade 3-4 adverse effects attributable to the intervention. While most of the assessed biomarkers improved during the follow-up in both arms, PMT25341-treated subjects did not experience any significant change, compared to placebo-treated subjects, in mean CD4+ T-cell count change (278 vs 250 cells/µL, P = .474) or CD4/CD8 ratio change (0.30 vs 0.32, P = .854). Similarly, we did not detect differences between treatment arms in secondary endpoints. Conclusions: In HIV-infected patients initiating ART at advanced disease, the clear immunological benefits of ART were not enhanced by this nutritional intervention targeting the gut-associated lymphoid tissue and microbiota. Clinical Trials Registration: NCT00870363.


Assuntos
Antirretrovirais/administração & dosagem , Dietoterapia/métodos , Infecções por HIV/terapia , Fatores Imunológicos/administração & dosagem , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , Adulto , Contagem de Linfócito CD4 , Relação CD4-CD8 , Terapia Combinada/métodos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Resultado do Tratamento , Adulto Jovem
8.
Enferm Infecc Microbiol Clin ; 37(6): 373-379, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30389268

RESUMO

BACKGROUND: The life expectancy of HIV-infected individuals has dramatically improved with potent antiretroviral therapies. However, organ-specific toxicities of some antiretrovirals and persistent inflammation and immune activation due to residual virus replication account for a high burden of age-associated comorbidities in the HIV population. METHODS: The prevalence of overt cardiovascular, renal and bone diseases as well as their major risk factors were cross-sectionally examined during the year 2014 in the VACH cohort, a large nationwide population of HIV-infected individuals in Spain. RESULTS: A total of 10,897 HIV-infected patients were examined. Seventy-one point four percent were male and the mean age was 48 years. Mean time since HIV diagnosis was 15.8 years and mean time on antiretroviral therapy was 13.1 years. The proportion of patients with undetectable viral load was 87.1%, whereas 65.7% had CD4 counts>500 cells/mm3. Overall, cardiovascular, renal and bone disease were recorded in 4.7%, 5.9% and 2.8%, respectively. The prevalence of major risk factors was as follows: smoking 51.3%, alcohol abuse 7.8%, overweight/obesity 42.2%, diabetes 19.9%, dyslipidaemia 72.6%, hypertension 25.6%, and osteoporosis 11.1%. In the subset of patients older than 55 years-old (18%), all figures for overt disease and their major risk factors were significantly greater. CONCLUSION: Major age-related medical conditions and most of their risk factors are highly prevalent in HIV-infected individuals on long-term antiretroviral therapy in Spain. Preventive actions, including careful selection of antiretroviral agents, should be prioritized in the ageing HIV population.

10.
Sci Rep ; 8(1): 15541, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30341387

RESUMO

A recent study has pointed out to CD32a as a potential biomarker of HIV-persistent CD4 cells. We have characterized the level and phenotype of CD32+ cells contained in different subsets of CD4 T-cells and its potential correlation with level of total HIV-DNA in thirty HIV patients (10 typical progressors naïve for cART, 10 cART-suppressed patients, and 10 elite controllers). Total HIV-DNA was quantified in different subsets of CD4 T-cells: Trm and pTfh cells. Level and immunephenotype of CD32+ cells were analyzed in these same subsets by flow cytometry. CD32 expression in Trm and pTfh subsets was similar in the different groups, and there was no significant correlation between the level of total HIV-DNA and the level of CD32 expression in these subsets. However, total HIV-DNA level was correlated with expression of CD127 (rho = -0.46, p = 0.043) and of CCR6 (rho = -0.418, p = 0.027) on CD32+ cells. Our results do not support CD32 as a biomarker of total HIV-DNA content. However, analyzing the expression of certain markers by CD32+ cells could improve the utility of this marker in the clinical setting, prompting the necessity of further studies to both validate our results and to explore the potential utility of certain markers expressed by CD32+ cells.


Assuntos
Antirretrovirais/uso terapêutico , Linfócitos T CD4-Positivos/virologia , DNA Viral/análise , Expressão Gênica , Infecções por HIV/patologia , HIV/crescimento & desenvolvimento , Receptores de IgG/análise , Adulto , Linfócitos T CD4-Positivos/química , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/química , Subpopulações de Linfócitos T/virologia , Carga Viral
11.
ISME J ; 12(8): 1964-1976, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29789624

RESUMO

HIV infection causes a disruption of gut-associated lymphoid tissue, driving a shift in the composition of gut microbiota. A deeper understanding of the metabolic changes and how they affect the interplay with the host is needed. Here, we assessed functional modifications of HIV-associated microbiota by combining metagenomic and metatranscriptomic analyses. The transcriptionally active microbiota was well-adapted to the inflamed environment, overexpressing pathways related to resistance to oxidative stress. Furthermore, gut inflammation was maintained by the Gram-negative nature of the HIV-associated microbiota and underexpression of anti-inflammatory processes, such as short chain fatty acid biosynthesis or indole production. We performed co-occurrence and metabolic network analyses that showed relevance in the microbiota structure of both taxonomic and metabolic HIV-associated biomarkers. The Bayesian network revealed the most determinant pathways for maintaining the structure stability of the bacterial community. In addition, we identified the taxa's contribution to metabolic activities and their interactions with host health.


Assuntos
Bactérias/metabolismo , Microbioma Gastrointestinal , Infecções por HIV/microbiologia , Bactérias/genética , Bactérias/isolamento & purificação , Teorema de Bayes , Doenças do Sistema Digestório/microbiologia , Humanos , Inflamação/microbiologia , Redes e Vias Metabólicas , Metagenômica , Transcriptoma
12.
Artigo em Inglês | IBECS | ID: ibc-176574

RESUMO

Osteoporosis has become an emerging comorbid condition in people living with HIV (PLWH). The increase in survival and the progressive aging of PLWH will make this complication more frequent in the near future. In addition to the traditional risk factors affecting the general population, factors directly or indirectly associated with HIV infection, including antiretroviral therapy, can increase the risk of osteoporosis. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of osteoporosis in PLWH. This document is intended for all professionals who work in clinical practice in the field of HIV infection


La osteoporosis se ha convertido en una situación comórbida emergente en las personas infectadas por VIH. El incremento de la supervivencia y el envejecimiento progresivo de las personas infectadas por VIH harán que esta complicación sea más frecuente en un futuro cercano. Además de los factores de riesgo tradicionales, los factores directa o indirectamente asociados a la infección por VIH, incluyendo el tratamiento antirretroviral, pueden incrementar el riesgo de presentar osteoporosis. El presente artículo constituye un resumen ejecutivo del documento que actualiza las recomendaciones previas sobre la prevención y el tratamiento de la osteoporosis en las personas infectadas por VIH. Este documento va dirigido a todos los profesionales que ejercen la práctica clínica en el campo de la infección por VIH


Assuntos
Humanos , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Osteoporose/induzido quimicamente , Medição de Risco , Fármacos Anti-HIV/uso terapêutico
13.
AIDS ; 32(10): 1229-1237, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29683848

RESUMO

OBJECTIVE: In a recent blinded randomized study, we found that in HIV-infected individuals a short supplementation with prebiotics (scGOS/lcFOS/glutamine) ameliorates dysbiosis of total gut bacteria, particularly among viremic untreated patients. Our study goal was to determine the fraction of the microbiota that becomes active during the intervention and that could provide additional functional information. DESIGN: A total of six healthy individuals, and 16 HIV-infected patients comprising viremic untreated patients (n = 5) and antiretroviral therapy-treated patients that are further divided into immunological responders (n = 7) and immunological nonresponders (n = 4) completed the 6-week course of prebiotic treatment, including six patients receiving a placebo. METHODS: Alpha and beta diversity of potentially active and total gut microbiota was evaluated using shotgun proteomics and 16S rRNA gene sequencing. RESULTS: HIV infection decreased dormancy and increased alpha diversity of active bacteria in comparison with the healthy controls, whose richness was not further influenced by the prebiotic intervention. The effect of the prebiotics was most evident at the beta-diversity of active bacteria, particularly within viremic untreated patients. We found that the prebiotics did not only ameliorate dysbiosis of total bacteria in viremic untreated patients but also increased the abundance of active bacteria with strong immunomodulatory properties and amino acids metabolism, namely Bifidobacteriaceae, at similar levels to those in healthy individuals. This effect was attenuated in ART-treated individuals. CONCLUSION: The effect of prebiotics was greater among ART-naive HIV-infected individuals than in ART-treated patients and healthy controls. This highlights the importance of therapies aimed at manipulating the microbiome in this group of patients.


Assuntos
Antirretrovirais/administração & dosagem , Bactérias/classificação , Bactérias/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por HIV/terapia , Prebióticos/administração & dosagem , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Seguimentos , Humanos , Pessoa de Meia-Idade , Filogenia , Placebos/administração & dosagem , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
14.
Lancet HIV ; 5(4): e162-e171, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29475804

RESUMO

BACKGROUND: Abacavir and tenofovir alafenamide offer reduced bone toxicity compared with tenofovir disoproxil fumarate. We aimed to compare safety and efficacy of tenofovir alafenamide plus emtricitabine with that of abacavir plus lamivudine. METHODS: In this randomised, double-blind, active-controlled, non-inferiority phase 3 trial, HIV-1-positive adults (≥18 years) were screened at 79 sites in 11 countries in North America and Europe. Eligible participants were virologically suppressed (HIV-1 RNA <50 copies per mL) and on a stable three-drug regimen containing abacavir plus lamivudine. Participants were randomly assigned (1:1) by a computer-generated allocation sequence (block size 4) to switch to fixed-dose tablets of tenofovir alafenamide (10 mg or 25 mg) plus emtricitabine (200 mg) or remain on abacavir (600 mg) plus lamivudine (300 mg), with matching placebo, while continuing to take the third drug. Randomisation was stratified by the third drug (boosted protease inhibitor vs other drug) at screening. Investigators, participants, and study staff giving treatment, assessing outcomes, and collecting data were masked to treatment group. The primary endpoint was the proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL) at week 48 (assessed by snapshot algorithm), with a 10% non-inferiority margin. We analysed the primary endpoint in participants enrolled before May 23, 2016 (when target sample size was reached), and we analysed safety in all enrolled participants who received at least one dose of study drug (including patients enrolled after these dates). This study was registered with ClinicalTrials.gov, number NCT02469246. FINDINGS: Study enrolment began on June 29, 2015, and the cutoff enrolment date for the week 48 primary endpoint analysis was May 23, 2016. 501 participants were randomly assigned and treated. At week 48, virological suppression was maintained in 227 (90%) of 253 participants receiving tenofovir alafenamide plus emtricitabine compared with 230 (93%) of 248 receiving abacavir plus lamivudine (difference -3·0%, 95% CI -8·2 to 2·0), showing non-inferiority. Few participants discontinued treatment because of adverse events: 12 (4%) of 280 participants in the tenofovir alafenimide plus emtricitabine group and nine (3%) of 276 in the abacavir plus lamivudine group. Three participants had serious, treatment-related adverse events: one each with renal colic and neutropenia in the tenofovir alafenamide plus emtricitabine group, and one myocardial infarction in the abacavir plus lamivudine group. There were no treatment-related deaths. INTERPRETATION: Tenofovir alafenamide, in combination with emtricitabine and various third drugs, maintained high efficacy with a renal and bone safety profile similar to that of abacavir. In virologically suppressed patients, a regimen containing tenofovir alafenamide could be an alternative to those containing abacavir, without concern for new onset of renal or bone toxicities or hyperlipidaemia. FUNDING: Gilead Sciences Inc.


Assuntos
Adenina/análogos & derivados , Antirretrovirais/administração & dosagem , Didesoxinucleosídeos/administração & dosagem , Emtricitabina/administração & dosagem , Infecções por HIV/tratamento farmacológico , Lamivudina/administração & dosagem , Tenofovir/administração & dosagem , Adenina/administração & dosagem , Adenina/efeitos adversos , Adulto , Idoso , Antirretrovirais/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Emtricitabina/efeitos adversos , Feminino , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tenofovir/efeitos adversos , Resultado do Tratamento , Carga Viral , Adulto Jovem
15.
Enferm Infecc Microbiol Clin ; 36(5): 312-314, 2018 05.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28579014

RESUMO

Osteoporosis has become an emerging comorbid condition in people living with HIV (PLWH). The increase in survival and the progressive aging of PLWH will make this complication more frequent in the near future. In addition to the traditional risk factors affecting the general population, factors directly or indirectly associated with HIV infection, including antiretroviral therapy, can increase the risk of osteoporosis. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of osteoporosis in PLWH. This document is intended for all professionals who work in clinical practice in the field of HIV infection.


Assuntos
Infecções por HIV/complicações , Osteoporose/etiologia , Osteoporose/prevenção & controle , Humanos , Osteoporose/diagnóstico , Guias de Prática Clínica como Assunto
16.
Sci Rep ; 7(1): 16799, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29196729

RESUMO

HIV latency is the main barrier to HIV eradication. Peripheral T follicular helper (pTfh) cells have a prominent role in HIV persistence. Herein, we analyzed the HIV reservoir size within memory CD4+ T-cell subsets in patients with HIV replication control. Twenty HIV-infected patients with suppressed HIV replication were included, with 10 elite controllers (EC) and 10 treated (TX) individuals. The HIV reservoir size was analyzed in resting memory CD4+ T-cells (Trm), pTfh, and non-pTfh cells using an ultrasensitive digital-droplet-PCR assay. Inter-group and intra-group differences were tested using non-parametric tests. Compared with the TX patients, the EC patients had smaller HIV reservoir not only in Trm but also in pTfh and non-pTfh subsets of memory CD4+ T-cells. The largest differences were observed in pTfh cells (p = 0.025). The pTfh and non-pTfh cells harbored similar levels of HIV-DNA in the EC (p = 0.60) and TX patients (p = 0.17); however, the contribution to HIV-DNA levels in memory CD4+ T-cells varied among the pTfh and non-pTfh subsets in both groups of patients. The EC patients showed smaller HIV reservoir in memory CD4+ cells, especially in the pTfh subset, a population of cells with a pivotal role in the antiviral immune response, suggesting a potential link between low levels of infection in pTfh cells and the ability of the EC patients to spontaneously control HIV replication.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Linfócitos T Auxiliares-Indutores/virologia , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/virologia , Estudos de Casos e Controles , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Infecções por HIV/virologia , HIV-1/genética , HIV-1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Carga Viral , Latência Viral
18.
AIDS ; 31(13): 1781-1795, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28537935

RESUMO

: There is a long-lasting controversy surrounding an association between abacavir (ABC) and an increased risk of cardiovascular disease in HIV-positive patients. Although differing in their specifics, a number of published cohort studies and clinical trials support such an association, usually relating it to recent exposure to the drug, independently of traditional predisposing factors. However, other clinical trials have failed to reveal such a relation and have pointed to methodological differences to explain discrepancies. Significantly, the controversy has been fueled by the lack of a credible mechanism of action to justify the putative detrimental actions of ABC. There is a myriad of contradictory clinical indicators which are not clearly compatible with known profiles of either vascular physiopathology or pharmacological interference. However, basic research has recently hinted at altered homeostatic mechanisms, though this requires clinical validation. In particular, recurrent evidence - both clinical and experimental - relates ABC with vascular inflammation, a leading contributor to the atherosclerotic plaque and thrombosis. ABC's chemical structure is very close to that of endogenous purines (ATP, ADP and AMP), major paracrine signaling molecules capable of triggering prothrombotic and proinflammatory vascular programs. Other proposed mechanisms are a competitive inhibition of guanylyl cyclase in platelets and a subsequent decrease in cyclic guanosine monophosphate (cGMP). The present review aims to shed light on this complex subject by summarizing and critically evaluating all the available clinical data regarding a relationship between ABC and cardiovascular disease, and to put forward potential pharmacological explanations compatible with both the clinical scenario and experimental findings.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/administração & dosagem , Aterosclerose/induzido quimicamente , Aterosclerose/fisiopatologia , Didesoxinucleosídeos/administração & dosagem , Humanos , Vasculite/induzido quimicamente , Vasculite/fisiopatologia
19.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 35(2): 88-99, feb. 2017. graf, tab
Artigo em Inglês | IBECS | ID: ibc-162048

RESUMO

Introduction: GESIDA and the AIDS National Plan panel of experts suggest preferred (PR), alternative (AR), and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for the year 2016. The objective of this study is to evaluate the costs and the efficacy of initiating treatment with these regimens. Methods: Economic assessment of costs and efficiency (cost/efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48 in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting is Spain and the costs correspond to those of 2016. A sensitivity deterministic analysis was conducted, building three scenarios for each regimen: base case, most favourable, and least favourable. Results: In the base case scenario, the cost of initiating treatment ranges from 4663 Euros for 3TC+LPV/r (OR) to 10,894 Euros for TDF/FTC+RAL (PR). The efficacy varies from 0.66 for ABC/3TC+ATV/r (AR) and ABC/3TC+LPV/r (OR), to 0.89 for TDF/FTC+DTG (PR) and TDF/FTC/EVG/COBI (AR). The efficiency, in terms of cost/efficacy, ranges from 5280 to 12,836 Euros per responder at 48 weeks, for 3TC+LPV/r (OR), and RAL+DRV/r (OR), respectively. Conclusion: Despite the overall most efficient regimen being 3TC+LPV/r (OR), among the PR and AR, the most efficient regimen was ABC/3TC/DTG (PR). Among the AR regimes, the most efficient was TDF/FTC/RPV (AU)


Introducción: El panel de expertos de GESIDA/Plan Nacional del Sida ha recomendado pautas preferentes (PP), pautas alternativas (PA) y otras pautas (OP) para el tratamiento antirretroviral (TARV) como terapia de inicio en pacientes infectados por VIH para 2016. El objetivo de este estudio es evaluar los costes y la eficiencia de iniciar tratamiento con estas pautas. Métodos: Evaluación económica de costes y eficiencia (coste/eficacia) mediante construcción de árboles de decisión. Se definió eficacia como la probabilidad de tener carga viral <50copias/ml en la semana 48 en análisis por intención de tratar. Se definió coste de iniciar tratamiento con una pauta como los costes del TARV y de todas sus consecuencias (efectos adversos, cambios de pauta y estudio de resistencias) que se producen en las siguientes 48 semanas. Se utilizó la perspectiva del Sistema Nacional de Salud, considerando solo costes directos diferenciales: TARV (a precio oficial), manejo de efectos adversos, estudios de resistencias y determinación de HLA B*5701. El ámbito es España, con costes de 2016. Se realizó análisis de sensibilidad determinista construyendo 3 escenarios para cada pauta: basal, más favorable y más desfavorable. Resultados: En el escenario basal, los costes de iniciar tratamiento oscilaron entre 4.663euros para 3TC+LPV/r (OP) y 10.894euros para TDF/FTC+RAL (PP). La eficacia osciló entre 0,66 para ABC/3TC+ATV/r (PA) y ABC/3TC+LPV/r (OP), y 0,89 para TDF/FTC+DTG (PP) y TDF/FTC/EVG/COBI (PA). La eficiencia, en términos de coste/eficacia, osciló entre 5.280 y 12.836euros por respondedor a las 48 semanas, para 3TC+LPV/r (OP) y RAL+DRV/r (OP), respectivamente. Conclusión: Aunque globalmente la pauta más eficiente fue 3TC+LPV/r (OP), considerando solamente las PP y las PA, la pauta más eficiente fue ABC/3TC/DTG (PP). De las PA, la más eficiente fue TDF/FTC/RPV (AU)


Assuntos
Humanos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Antirretrovirais/uso terapêutico , Análise Custo-Benefício , Custos de Medicamentos/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Síndrome de Imunodeficiência Adquirida/prevenção & controle
20.
Enferm Infecc Microbiol Clin ; 35(2): 88-99, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27459919

RESUMO

INTRODUCTION: GESIDA and the AIDS National Plan panel of experts suggest preferred (PR), alternative (AR), and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for the year 2016. The objective of this study is to evaluate the costs and the efficacy of initiating treatment with these regimens. METHODS: Economic assessment of costs and efficiency (cost/efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48 in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting is Spain and the costs correspond to those of 2016. A sensitivity deterministic analysis was conducted, building three scenarios for each regimen: base case, most favourable, and least favourable. RESULTS: In the base case scenario, the cost of initiating treatment ranges from 4663 Euros for 3TC+LPV/r (OR) to 10,894 Euros for TDF/FTC+RAL (PR). The efficacy varies from 0.66 for ABC/3TC+ATV/r (AR) and ABC/3TC+LPV/r (OR), to 0.89 for TDF/FTC+DTG (PR) and TDF/FTC/EVG/COBI (AR). The efficiency, in terms of cost/efficacy, ranges from 5280 to 12,836 Euros per responder at 48 weeks, for 3TC+LPV/r (OR), and RAL+DRV/r (OR), respectively. CONCLUSION: Despite the overall most efficient regimen being 3TC+LPV/r (OR), among the PR and AR, the most efficient regimen was ABC/3TC/DTG (PR). Among the AR regimes, the most efficient was TDF/FTC/RPV.


Assuntos
Fármacos Anti-HIV/economia , Fármacos Anti-HIV/uso terapêutico , Análise Custo-Benefício , Infecções por HIV/tratamento farmacológico , Infecções por HIV/economia , Humanos , Guias de Prática Clínica como Assunto , Espanha
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