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BACKGROUND: Severe non-AIDS bacterial infections (SBIs) are among the leading causes of hospital admissions among persons with human immunodeficiency virus (PWH) in regions with high antiretroviral therapy coverage. METHODS: This large prospective cohort study of PWH examined the types of infections, bacterial documentation, and evolution of antibiotic resistance among PWH hospitalized with SBIs over an 18-year period. RESULTS: Between 2000 and 2017, 459 PWH had at least 1 SBI with bacterial documentation. Among the 847 SBIs, there were 280 cases of bacteremia, 269 cases of pneumonia, and 240 urinary tract infections. The 1025 isolated bacteria included Enterobacteriaceae (n = 394; mainly Escherichia coli), Staphylococcus aureus (n = 153), and Streptococcus pneumoniae (n = 82). The proportion of S. pneumoniae as the causative agent in pneumonia and bacteremia decreased sharply over time, from 34% to 8% and from 21% to 3%, respectively. The overall antibiotic resistance of S. aureus and S. pneumoniae decreased progressively but it increased for Enterobacteriaceae (from 24% to 48% for amoxicillin-clavulanate, from 4% to 18% for cefotaxime, and from 5% to 27% for ciprofloxacin). Cotrimoxazole prophylaxis was associated with higher nonsusceptibility of S. pneumoniae to amoxicillin and erythromycin, higher nonsusceptibility of Enterobacteriaceae to ß-lactams and fluoroquinolones, and a higher risk of extended-spectrum ß-lactamase-producing Enterobacteriaceae. CONCLUSIONS: The bacterial resistance pattern among PWH between 2014 and 2017 was broadly similar to that in the general population, with the exception of a higher resistance profile of Enterobacteriaceae to fluoroquinolones. The use of cotrimoxazole as prophylaxis was associated with an increased risk of antibiotic resistance.
Assuntos
Síndrome da Imunodeficiência Adquirida , Bacteriemia , Infecções Estafilocócicas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol , HIV , Staphylococcus aureus , Estudos Prospectivos , Farmacorresistência Bacteriana , Bactérias , Enterobacteriaceae , Escherichia coli , Infecções Estafilocócicas/tratamento farmacológico , Fluoroquinolonas , Combinação Amoxicilina e Clavulanato de Potássio , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Bacteriemia/epidemiologia , Bacteriemia/tratamento farmacológico , Testes de Sensibilidade Microbiana , beta-LactamasesRESUMO
BACKGROUND: Combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir has been suggested as an approach to improve the outcome of patients with moderate/severe COVID-19 infection. OBJECTIVES: To examine the safety of combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. METHODS: This was an observational cohort study of patients hospitalized for COVID-19 pneumonia treated with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. Clinical evaluations, electrocardiograms and the pharmacokinetics of hydroxychloroquine, darunavir and lopinavir were examined according to clinical practice and guidelines. RESULTS: Twenty-one patients received hydroxychloroquine with lopinavir/ritonavir (median age 68 years; 10 males) and 25 received hydroxychloroquine with darunavir/ritonavir (median age 71 years; 15 males). During treatment, eight patients (17.4%) developed ECG abnormalities. Ten patients discontinued treatment, including seven for ECG abnormalities a median of 5 (range 2-6) days after starting treatment. All ECG abnormalities reversed 1-2 days after interrupting treatment. Four patients died within 14 days. ECG abnormalities were significantly associated with age over 70 years, coexisting conditions (such as hypertension, chronic cardiovascular disease and kidney failure) and initial potential drug interactions, but not with the hydroxychloroquine concentration. CONCLUSIONS: Of the patients with COVID-19 who received hydroxychloroquine with lopinavir or darunavir, 17% had ECG abnormalities, mainly related to age or in those with a history of cardiovascular disease.
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Antivirais/efeitos adversos , Tratamento Farmacológico da COVID-19 , Darunavir/efeitos adversos , Hidroxicloroquina/efeitos adversos , Lopinavir/efeitos adversos , Antivirais/administração & dosagem , Antivirais/sangue , Antivirais/uso terapêutico , COVID-19/epidemiologia , Estudos de Coortes , Darunavir/administração & dosagem , Darunavir/sangue , Darunavir/uso terapêutico , Quimioterapia Combinada , Eletrocardiografia , França , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/sangue , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Lopinavir/administração & dosagem , Lopinavir/sangue , Lopinavir/uso terapêutico , SARS-CoV-2 , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Whipple's disease usually presents as chronic joint pain followed by digestive manifestations. However, many different presentations have been described in the literature. We report here the first proven case of muscular vasculitis related to Whipple's disease, associated with an expansion of circulating activated γδ T lymphocytes.
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Granulomatose com Poliangiite/complicações , Contagem de Linfócitos , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Doença de Whipple/complicações , Doença de Whipple/imunologia , Antibacterianos/uso terapêutico , Biomarcadores , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Sintomas , Resultado do Tratamento , Doença de Whipple/diagnóstico , Doença de Whipple/tratamento farmacológicoRESUMO
BACKGROUND: Current clinical guidelines consider regimens consisting of either ritonavir-boosted atazanavir or ritonavir-boosted lopinavir and a nucleoside reverse transcriptase inhibitor (NRTI) backbone among their recommended and alternative first-line antiretroviral regimens. However, these guidelines are based on limited evidence from randomized clinical trials and clinical experience. METHODS: We compared these regimens with respect to clinical, immunologic, and virologic outcomes using data from prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States in the HIV-CAUSAL Collaboration, 2004-2013. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started a lopinavir or an atazanavir regimen. We estimated the 'intention-to-treat' effect for atazanavir vs lopinavir regimens on each of the outcomes. RESULTS: A total of 6668 individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53-.91) for death, 0.67 (95% CI, .55-.82) for AIDS-defining illness or death, and 0.91 (95% CI, .84-.99) for virologic failure at 12 months. The mean 12-month increase in CD4 count was 8.15 (95% CI, -.13 to 16.43) cells/µL higher in the atazanavir group. Estimates differed by NRTI backbone. CONCLUSIONS: Our estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a greater 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for atazanavir compared with lopinavir regimens.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Sulfato de Atazanavir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lopinavir/uso terapêutico , Adolescente , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Comportamento Cooperativo , Países Desenvolvidos , Europa (Continente) , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Estados Unidos , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Central catheter-related bloodstream infections (CRBIs) can lead to severe complications, including suppurative thrombophlebitis, endocarditis, and metastatic infections. While complications due to CRBIs caused by Staphylococcus aureus (SA) are well-known, there are limited data regarding CRBIs caused by other bacteria. METHODS: This 2-year retrospective single-center study of patients with CRBIs from a tertiary care hospital examined the hematogenous complications associated with CRBIs according to patient characteristics, central venous catheter (CVC) types, and causative bacteria. RESULTS: All in all, 254 patients with confirmed CRBIs were included; 285 bacteria types were isolated, mainly Enterobacteriaceae (n = 94), coagulase-negative Staphylococci (CNS, n = 82), SA (n = 45), and non-fermenting Gram-negative bacteria (NGB, n = 45). Among the patients, 35 developed at least one hematogenous complication (14 %), including suppurative thrombophlebitis (n = 15), endocarditis (n = 7) and metastatic infections (n = 16). In multivariate analysis, hemodialysis, persistent bacteremia for at least 3 days, and CRBIs caused by SA were associated with increased risk for hematogenous complications, while previous curative anticoagulant treatment was associated with reduced risk. Diabetes, CVC maintenance, and hematogenous complications were associated with increased 3-month mortality. CONCLUSION: A thorough investigation of hematogenous complications should be envisioned in patients with persistent bacteremia, particularly those with SA infections and those on hemodialysis.
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Bacteriemia , Cateteres Venosos Centrais , Endocardite , Infecções Estafilocócicas , Tromboflebite , Humanos , Cateteres Venosos Centrais/efeitos adversos , Estudos Retrospectivos , Staphylococcus aureus , Fatores de Risco , Tromboflebite/etiologia , Tromboflebite/complicações , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Endocardite/complicaçõesRESUMO
INTRODUCTION: Hearing loss is a rare manifestation in giant cell arteritis. The different types of deafness are possible with a predominance of sensorineural deafness. CASE REPORT: We report a 75-year-old woman who presented with typical manifestations of giant cell arteritis associated concomitantly with the occurrence of bilateral mixed hearing loss confirmed on the audiogram. Corticosteroids allowed a rapidly favorable clinical and biological outcome. The follow-up audiogram at 3 months was markedly improved and showed a decrease in sensorineural hearing loss and disappearance of conductive hearing loss. CONCLUSION: Any rapid onset deafness in an inflammatory context in the elderly should lead to a search for giant cell arteritis. The diagnosis can be difficult in the absence of other typical manifestations, especially since the biopsy of the temporal artery most often comes back negative. Corticosteroids are usually effective.
Assuntos
Surdez , Arterite de Células Gigantes , Perda Auditiva Neurossensorial , Feminino , Humanos , Idoso , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/epidemiologia , Artérias Temporais/patologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Corticosteroides , Surdez/complicações , Surdez/patologiaAssuntos
Fármacos Anti-HIV/administração & dosagem , Cobicistat/administração & dosagem , Emtricitabina/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Quinolonas/administração & dosagem , Tenofovir/administração & dosagem , Adulto , Sangue/virologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Secundária/métodos , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND & AIMS: HIV and viral hepatitis co-infected patients are at high risk for hepatocarcinoma. The contribution of immunodeficiency is not well documented. We aimed at estimating the relationship between the occurrence of hepatocarcinoma and both types of measures of immunodeficiency, current and cumulative (time below a given threshold), to assess their independent effects. METHODS: HIV-infected adults included in the ANRS CO3 Aquitaine Cohort with no history of cancer, ≥ 3 months of follow-up between 1998 and 2008, ≥ 1 CD4+ cell count (CD4+), and documented hepatitis virus status were eligible. Extended Cox proportional hazards models with delayed entry were used to estimate the risk of hepatocarcinoma. Exposure to a CD4+ < 350 or <500 cells/mm(3) (current and cumulative duration) was time-updated. Hepatitis B or C virus co-infection and gender were fixed-effect variables. RESULTS: Sixteen cases of hepatocarcinoma were diagnosed among the 2864 eligible patients, the incidence rate was 0.78 case/1000 person-years (95% Confidence Interval [CI]: 0.40-1.16). Current CD4+ < 350 or < 500 was independently associated with a higher risk of hepatocarcinoma (Hazard Ratio [HR]: 5.0, CI 1.5-16.8, p = 0.009 and HR = 10.3, CI 1.3-82.8, p = 0.029, respectively). The occurrence of hepatocarcinoma was independent of the cumulative exposure to a CD4+ < 350 or < 500 (p = 0.38 or p = 0.80, respectively). CONCLUSIONS: Presenting with CD4+ < 500 was associated with a higher risk of hepatocarcinoma, whereas the cumulative duration with immunodeficiency was not. These results suggest that moving CD4+ count above 500 following antiretroviral therapy initiation is associated with a decreased risk of hepatocarcinoma, regardless of the duration of HIV-induced immunodeficiency.
Assuntos
Contagem de Linfócito CD4 , Carcinoma Hepatocelular/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Neoplasias Hepáticas/epidemiologia , Adulto , Antirretrovirais/uso terapêutico , Carcinoma Hepatocelular/imunologia , Coinfecção/complicações , Feminino , França/epidemiologia , Infecções por HIV/tratamento farmacológico , Hepacivirus , Hepatite B/complicações , Vírus da Hepatite B , Hepatite C/complicações , Humanos , Incidência , Neoplasias Hepáticas/imunologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVES: Bacterial infections remain one of the main causes of morbidity and death in people living with HIV (PLHIV) in the most recent years. Several studies have demonstrated a protective effect of statins in the primary prevention of bacterial infections in other immunocompromised populations, but this effect remains controversial. The objective of this study was to evaluate the effect of statin use on the occurrence of a first episode of severe bacterial infection (SBI) in PLHIV in the ANRS CO3 Aquitaine cohort between 2000 and 2018. METHODS: All individuals included in the prospective ANRS CO3 Aquitaine cohort who had at least two follow-up visits between 2000 and 2018 were included. The primary endpoint was the occurrence of a first episode of bacterial infection leading to hospitalization of ≥48 hours or death. Statin exposure was updated during follow-up. Marginal Cox structural models were developed to consider the potential indication bias and time-dependent confusion. Numerous sensitivity analyses were carried out. RESULTS: In this study 51 658 person-years were followed. The overall incidence of a first episode of SBI was 12.4/1000 person-years. No effect of statins on the occurrence of SBI was demonstrated when subjects were considered on statins throughout their follow-up after treatment initiation (HR = 0.97; 95%CI: 0.75-1.25). The results were similar for the effect of statins on the risk of pneumonia and for all sensitivity analyses. CONCLUSION: In this large cohort of PLHIV with 18 years of follow-up and a high risk of severe infections, we found no effect of statins on the risk of occurrence of SBI or pneumonia.
Assuntos
Infecções Bacterianas , Infecções por HIV , Inibidores de Hidroximetilglutaril-CoA Redutases , Pneumonia , Infecções Bacterianas/complicações , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pneumonia/complicações , Estudos ProspectivosRESUMO
BACKGROUND: The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING: Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS: Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest. We evaluated 4 neuroAIDS conditions: HIV dementia and the opportunistic infections toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy. For each outcome, we estimated hazard ratios for atazanavir, lopinavir, and darunavir compared with efavirenz via a pooled logistic model. Our models were adjusted for baseline demographic and clinical characteristics. RESULTS: Twenty six thousand one hundred seventy-two individuals initiated efavirenz, 5858 initiated atazanavir, 8479 initiated lopinavir, and 4799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% confidence intervals) were 1.72 (1.00 to 2.96) for atazanavir, 2.21 (1.38 to 3.54) for lopinavir, and 1.41 (0.61 to 3.24) for darunavir. The respective hazard ratios (95% confidence intervals) for the combined end point were 1.18 (0.74 to 1.88) for atazanavir, 1.61 (1.14 to 2.27) for lopinavir, and 1.36 (0.74 to 2.48) for darunavir. The results varied in subsets defined by calendar year, nucleoside reverse transcriptase inhibitor backbone, and age. CONCLUSION: Our results are consistent with an increased risk of neuroAIDS after initiating lopinavir compared with efavirenz, but temporal changes in prescribing trends and confounding by indication could explain our findings.
Assuntos
Complexo AIDS Demência/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/epidemiologia , Meningite Criptocócica/epidemiologia , Toxoplasmose/epidemiologia , Adulto , Alcinos , América/epidemiologia , Sulfato de Atazanavir/uso terapêutico , Benzoxazinas/uso terapêutico , Estudos de Coortes , Ciclopropanos , Darunavir/uso terapêutico , Europa (Continente)/epidemiologia , Feminino , Inibidores da Protease de HIV/uso terapêutico , Humanos , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
We describe the effect of interleukin 6 (IL-6) blockade using tocilizumab (TCZ) for inducing and maintaining remission of refractory polyarteritis nodosa (PAN). Three patients with refractory PAN defined according to the American College of Rheumatology criteria were treated with TCZ infusions (8 mg/kg) on a monthly basis. All of them had severe cutaneous and articular involvement with elevated biological inflammatory markers. One suffered from a neuritis multiplex and one from renal and digestive damage. All three patients were dependent on high doses of glucocorticoids (above 0.5 mg/kg) and two of them were resistant to immunosuppressive drugs. All patients achieved and maintained clinical response and normalisation of the inflammation acute-phase proteins after a few weeks of treatment with TCZ. Prednisolone could be reduced by an average of 41-13 mg/day. These first case reports suggest that IL-6 blockade using TCZ could be a therapeutic alternative to induce remission in patients with polyarteritis nodosa resistant or intolerant to the reference treatment.
RESUMO
BACKGROUND: Clinical guidelines recommend immediate initiation of combined antiretroviral therapy for all HIV-positive individuals. However, those guidelines are based on trials of relatively young participants. METHODS: We included HIV-positive antiretroviral therapy-naive, AIDS-free individuals aged 50-70 years after 2004 in the HIV-CAUSAL Collaboration. We used the parametric g-formula to estimate the 5-year risk of all-cause and non-AIDS mortality under (1) immediate initiation at baseline and initiation at CD4 count, (2) <500 cells/mm, and (3) <350 cells/mm. Results were presented separately for the general HIV population and for a US Veterans cohort with high mortality. RESULTS: The study included 9596 individuals (28% US Veterans) with median (interquantile range) age of 55 (52-60) years and CD4 count of 336 (182-513) at baseline. The 5-year risk of all-cause mortality was 0.40% (95% confidence interval (CI): 0.10 to 0.71) lower for the general HIV population and 1.61% (95% CI: 0.79 to 2.67) lower for US Veterans when comparing immediate initiation vs initiation at CD4 <350 cells/mm. The 5-year risk of non-AIDS mortality was 0.17% (95% CI: -0.07 to 0.43) lower for the general HIV population and 1% (95% CI: 0.31 to 2.00) lower for US Veterans when comparing immediate initiation vs initiation at CD4 <350 cells/mm. CONCLUSIONS: Immediate initiation seems to reduce all-cause and non-AIDS mortality in patients aged 50-70 years.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Idoso , Contagem de Linfócito CD4 , Esquema de Medicação , Feminino , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estados Unidos/epidemiologia , Carga ViralRESUMO
Severe non-AIDS bacterial infections (SBI) are the leading cause of hospital admissions among people living with HIV (PLHIV) in industrialized countries. We aimed to estimate the incidence of SBI and their risk factors in a large prospective cohort of PLHIV patients over a 13-year period in France. Patients followed up in the ANRS CO3 Aquitaine cohort between 2000 and 2012 were eligible; SBI was defined as a clinical diagnosis associated with hospitalization of ≥48 hours or death. Survival analysis was conducted to identify risk factors for SBI.Total follow-up duration was 39,256 person-years [PY] (31,370 PY on antiretroviral treatment [ART]). The incidence of SBI decreased from 26.7/1000 PY [95% CI: 22.9-30.5] over the period 2000-2002 to 11.9/1000 PY [10.1-13.8] in 2009-2012 (p <0.0001). Factors independently associated to increased risk of SBI were: plasma HIVRNA>50 copies/mL (Hazard Ratio [HR] = 5.1, 95% Confidence Interval: 4.2-6.2), CD4 count <500 cells/mm3 and CD4/CD8 ratio <0.8 (with a dose-response relationship for both markers), history of cancer (HR = 1.4 [1.0-1.9]), AIDS stage (HR = 1.7 [1.3-2.1]) and HCV coinfection (HR = 1.4, [1.1-1.6]). HIV-positive patients with diabetes were more prone to SBI (HR = 1.6 [0.9-2.6]). Incidence of SBI decreased over a 13-year period due to the improvement in the virological and immune status of PLHIV on ART. Risk factors for SBI include low CD4 count and detectable HIV RNA, but also CD4/CD8 ratio, HCV coinfection, history of cancer and diabetes, comorbid conditions that have been frequent among PLHIV in recent years.
Assuntos
Infecções Bacterianas/complicações , Infecções por HIV/complicações , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , França/epidemiologia , HIV-1/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Carga ViralRESUMO
OBJECTIVE: To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and virologic outcomes. DESIGN: Prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States included in the HIV-CAUSAL Collaboration. METHODS: HIV-positive, antiretroviral therapy-naive, and acquired immune deficiency syndrome (AIDS)-free individuals were followed from the time they started an atazanavir or efavirenz regimen. We estimated an analog of the "intention-to-treat" effect for efavirenz versus atazanavir regimens on clinical, immunologic, and virologic outcomes with adjustment via inverse probability weighting for time-varying covariates. RESULTS: A total of 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths) and 18,786 individuals started an efavirenz regimen (389 deaths, 825 AIDS-defining illnesses or deaths). During a median follow-up of 31 months, the hazard ratios (95% confidence intervals) were 0.98 (0.77, 1.24) for death and 1.09 (0.91, 1.30) for AIDS-defining illness or death comparing efavirenz with atazanavir regimens. The 5-year survival difference was 0.1% (95% confidence interval: -0.7%, 0.8%) and the AIDS-free survival difference was -0.3% (-1.2%, 0.6%). After 12 months, the mean change in CD4 cell count was 20.8 (95% confidence interval: 13.9, 27.8) cells/mm lower and the risk of virologic failure was 20% (14%, 26%) lower in the efavirenz regimens. CONCLUSION: Our estimates are consistent with a smaller 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with atazanavir regimens. No overall differences could be detected with respect to 5-year survival or AIDS-free survival.
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Sulfato de Atazanavir/administração & dosagem , Benzoxazinas/administração & dosagem , Soropositividade para HIV/tratamento farmacológico , HIV-1/fisiologia , Carga Viral , Adulto , Alcinos , Ciclopropanos , Relação Dose-Resposta a Droga , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Inibidores da Protease de HIV/administração & dosagem , Soropositividade para HIV/epidemiologia , Soropositividade para HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Transcriptase Reversa/administração & dosagem , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Background: When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy). Methods: We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting. Results: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death. Conclusions: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Contagem de Linfócito CD4 , Feminino , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Análise de Sobrevida , Reino Unido/epidemiologia , Carga ViralRESUMO
BACKGROUND: We assessed the association of persistent low-level viraemia between 50-199 copies/ml (LLV) with the risk of virological failure (VF) among HIV-1-infected patients receiving combination antiretroviral therapy (ART). METHODS: ART-naive and ART-experienced patients followed up in the ANRS-CO3 Aquitaine Cohort were included if they started two nucleoside reverse transcriptase inhibitors (NRTIs) with either one non-nucleoside reverse transcriptase inhibitor (NNRTI) or one protease inhibitor boosted with ritonavir (PI/r) between 2000 and 2011 and achieved viral load (VL)<200 copies/ml 4-8 months after initiating ART. VF was defined as either two consecutive VL≥200 copies/ml or one VL≥200 followed by a modification of ART. LLV was defined as at least two consecutive VLs between 50-199 copies/ml for at least one month. We used Cox models to estimate the association of LLV with VF. RESULTS: Among 2,374 patients with a median follow-up of 3 years, 205 (8.6%) experienced LLV. LLV was strongly associated with further VF (adjusted hazard ratio [aHR] 2.30, 95% CI 1.65, 3.20). LLV was associated with VF in ART-experienced patients (aHR 3.02, 95% CI 2.10, 4.33) but not in ART-naive patients. Neither type of ART regimen (PI/r- versus NNRTI-based regimen) nor cumulative duration of LLV was associated with VF. CONCLUSIONS: Persistent LLV between 50-199 copies/ml was associated with VF among ART-experienced patients under ART. LLV between 50-199 copies/ml in ART-experienced patients should lead, after assessing patient's adherence and checking for drug interactions, to a closer monitoring and to consider ART optimization.
Assuntos
Fármacos Anti-HIV/uso terapêutico , DNA Viral/antagonistas & inibidores , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Viremia/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , DNA Viral/genética , Feminino , Seguimentos , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Falha de Tratamento , Carga Viral/efeitos dos fármacos , Viremia/virologiaRESUMO
OBJECTIVES: The current study aimed at describing the distribution and characteristics of malignancy related deaths in human immunodeficiency virus (HIV) infected patients in 2010 and at comparing them to those obtained in 2000 and 2005. METHODS: Data were obtained from three national surveys conducted in France in 2010, 2005 and 2000. The underlying cause of death was documented using a standardized questionnaire fulfilled in French hospital wards involved in the management of HIV infection. RESULTS: Among the 728 deaths reported in 2010, 262 were cancer-related (36%). After a significant increase from 28% in 2000 to 33% in 2005 and 36% in 2010, cancers represent the leading cause of mortality in HIV infected patients. The proportion of deaths attributed to non-AIDS/non-hepatitis-related cancers significantly increased from 2000 to 2010 (11% of the deaths in 2000, 17% in 2005 and 22% in 2010, p<0.001), while those attributed to AIDS-defining cancers decreased during the same period (16% in 2000, 13% in 2005 and 9% in 2010, p = 0.024). Particularly, the proportion of respiratory cancers significantly increased from 5% in 2000 to 6% in 2005 and 11% in 2010 (p = 0.004). Lung cancer was the most common cancer-related cause of death in 2010 (instead of non-Hodgkin lymphoma so far) and represented the leading cause of death in people living with HIV overall. CONCLUSIONS: Cancer prevention (especially smoking cessation), screening strategies and therapeutic management need to be optimized in HIV-infected patients in order to reduce mortality, particularly in the field of respiratory cancers.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/mortalidade , Neoplasias/complicações , Neoplasias/mortalidade , Adulto , Causas de Morte , Feminino , França/epidemiologia , HIV/isolamento & purificação , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologiaRESUMO
OBJECTIVES: We studied the link between T-cell activation, differentiation and senescence phenotypes and non-AIDS-related comorbidities in HIV-suppressed patients. DESIGN: Patients included in the ANRS CO3 Aquitaine Cohort were consecutively enrolled in this cross-sectional study between October 2011 and May 2013 called Chronic Immune Activation and Senescence (CIADIS) study. METHODS: We summarized immune markers [CD4 and CD8 activation (DR), differentiation (naive and terminally differentiated memory T cells), and senescence (CD57CD28)] in a weighted immune score by principal component analysis called CIADIS. Previously described Veterans Aging Cohort Study (VACS) index and immune risk profile (IRP) scores were calculated. We used adjusted logistic regression to assess the association between the CIADIS score and the presence of at least three non-AIDS-defining comorbidities. RESULTS: Of 876 patients with an undetectable viral load, 73.4% were men and median age was 50.5 years [interquartile range (IQR) 44.7-56.7 years]. Median CD4 T-cell count was 579/µl (IQR 429-759âcells/µl), and median duration of HIV viral suppression was 5.3 years (IQR 2.3-8.7). The weighted CIADIS score was associated with at least three comorbidities (odds ratio 1.3 for 1 SD more, 95% confidence interval 1.0, 1.6) independently of age, sex, AIDS stage, and the Veterans Aging Cohort Study score. The CIADIS and the immune risk profile scores were significantly associated with at least three comorbidities in adjusted models restricted to patients younger than 60 years. None of the tested scores were associated with at least three comorbidities in patients older than 60 years. CONCLUSIONS: The weighted CIADIS score based on activation, senescence, and differentiation markers might help physicians identifying patients at a higher risk for non-AIDS-related comorbidities.
Assuntos
Diferenciação Celular , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Ativação Linfocitária , Linfócitos T/imunologia , Adulto , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The goal of antiretroviral therapy (ART) is to reduce HIV-related morbidity and mortality by suppressing HIV replication. The prognostic value of persistent low-level viremia (LLV), particularly for clinical outcomes, is unknown. OBJECTIVE: Assess the association of different levels of LLV with virological failure, AIDS event, and death among HIV-infected patients receiving combination ART. METHODS: We analyzed data from 18 cohorts in Europe and North America, contributing to the ART Cohort Collaboration. Eligible patients achieved viral load below 50â copies/ml within 3-9 months after ART initiation. LLV50-199 was defined as two consecutive viral loads between 50 and 199â copies/ml and LLV200-499 as two consecutive viral loads between 50 and 499â copies/ml, with at least one between 200 and 499â copies/ml. We used Cox models to estimate the association of LLV with virological failure (two consecutive viral loads at least 500â copies/ml or one viral load at least 500âcopies/ml, followed by a modification of ART) and AIDS event/death. RESULTS: Among 17â902 patients, 624 (3.5%) experienced LLV50-199 and 482 (2.7%) LLV200-499. Median follow-up was 2.3 and 3.1 years for virological and clinical outcomes, respectively. There were 1903 virological failure, 532 AIDS events and 480 deaths. LLV200-499 was strongly associated with virological failure [adjusted hazard ratio (aHR) 3.97, 95% confidence interval (CI) 3.05-5.17]. LLV50-199 was weakly associated with virological failure (aHR 1.38, 95% CI 0.96-2.00). LLV50-199 and LLV200-499 were not associated with AIDS event/death (aHR 1.13, 95% CI 0.81-1.68; and aHR 0.95, 95% CI 0.62-1.48, [corrected] respectively). CONCLUSION: LLV200-499 was strongly associated with virological failure, but not with AIDS event/death. Our results support the US guidelines, which define virological failure as a confirmed viral load above 200 âcopies/ml.
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Carga Viral , Viremia , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Europa (Continente) , Feminino , Infecções por HIV/mortalidade , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Prognóstico , Análise de Sobrevida , Resultado do TratamentoRESUMO
There are no data on how to manage implantable intra-arterial catheter (IAC) infections. We report the case of a patient with liver metastases of colon cancer treated by regional intra-arterial chemotherapy who presented a suspected IAC-related infection, in whom daptomycin systemic treatment and lock therapy allowed to cure the IAC infection.