RESUMO
PURPOSE: SARS-CoV-2 infection produces lymphopenia and CD4+ T-cell decrease, which could lead to a higher risk of bacterial co-infection or impair immunological evolution in people living with HIV (PLWH). METHODS: We investigated the rate of co-infection and superinfection, and the evolution of CD4+ count and CD4+/CD8+ ratio, in hospitalized PLWH with COVID-19. RESULTS: From March to December 2020, 176 PLWH had symptomatic COVID-19 and 62 required hospitalization (median age, 56 years, 89% males). At admission, 7% and 13% of patients had leukocytosis or increased procalcitonin values and 37 (60%) received empiric antibiotic therapy, but no bacterial co-infection was diagnosed. There were seven cases of superinfection (12%), and one case of P. jiroveci pneumonia during ICU stay. No significant change in CD4+ count or CD4+/CD8+ ratio was observed after discharge. CONCLUSION: Bacterial co-infection is not frequent in PLWH with COVID-19. Immune recovery is observed in most of patients after the disease.
Assuntos
COVID-19 , Infecções por HIV , Infecções Bacterianas/epidemiologia , COVID-19/epidemiologia , COVID-19/imunologia , Coinfecção/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Terapia de Imunossupressão/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Medição de RiscoRESUMO
BACKGROUND: Darunavir/cobicistat can be used as mono, dual, triple or more than triple therapy. OBJECTIVES: To assess factors associated with the number of drugs in darunavir/cobicistat regimens. METHODS: A nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat in Spain from July 2015 to May 2017. Baseline characteristics, efficacy and safety at 48 weeks were compared according to the number of drugs used. RESULTS: There were 761 patients (75% men, 98% were antiretroviral-experienced, 32% had prior AIDS, 84% had HIV RNA <50 copies/mL and 88% had ≥200 CD4 cells/mm3) who initiated darunavir/cobicistat as mono (n=308, 40%), dual (n=173, 23%), triple (n=253, 33%) or four-drug (n=27, 4%) therapy. Relative to monotherapy, triple therapy was more common in men aged <50 years, with prior AIDS and darunavir plus ritonavir use, and with CD4 cells <200/mm3 and with detectable viral load at initiation of darunavir/cobicistat; dual therapy was more common with previous intravenous drug use, detectable viral load at initiation of darunavir/cobicistat and no prior darunavir plus ritonavir; and four-drug therapy was more common with prior AIDS and detectable viral load at initiation of darunavir/cobicistat. Monotherapy and dual therapy showed a trend to better virological responses than triple therapy. CD4 responses and adverse effects did not differ among regimens. DISCUSSION: Darunavir/cobicistat use in Spain has been tailored according to clinical characteristics of HIV-infected patients. Monotherapy and dual therapy have been common and preferentially addressed to older patients with a better HIV status, suggesting that health issues other than HIV infection may have been strong determinants of its prescription.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Cobicistat/uso terapêutico , Darunavir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adulto , Fatores Etários , Quimioterapia Combinada , Feminino , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Carga Viral/efeitos dos fármacosRESUMO
Background and Objectives: HIV patients have seen accelerated ageing. Our objective was to determine the prevalence of frailty, to evaluate factors associated with frailty and to evaluate physical function in older HIV-infected adults. Design: this was a cross-sectional study. Setting: outpatient clinics of two public university hospitals in Madrid (Spain). Methods: frailty was defined according to the criteria of Fried: shrinking, weakness, poor endurance and energy, slowness and low physical activity level, being frail those who met at least three criteria, prefrail one or two criteria and robust when they met no criteria. Physical function was assessed using standardised methods. Results: we evaluated 117 HIV-infected patients. Mean age was 61.3 ([standard deviation] 6.87) years. All patients were on antiretroviral therapy. Median current CD4+ T-cell count was 638 (144-1871) cells/µl, and median CD4/CD8 ratio was 0.79 (0.00-3.62). The prevalence of frailty was 15.4%, and that of prefrailty was 52.1%. In the multivariate analyses depressive symptoms (OR [95% CI], 9.20 [2.17-39.05]) and CD4/CD8 ratio (OR 0.11 [0.02-0.61]) were associated with frailty. Even though 100% of the patients were able to walk and perform basic activities of daily life independently, functional impairment was high (20% slow gait and 55% Short Physical Performance Battery ≤9). Conclusions: HIV-infected patients aged ≥55 years have a high prevalence of frailty and a high burden of functional impairment. Optimal management of this population requires close collaboration between infectious diseases specialists and geriatricians.
Assuntos
Envelhecimento , Idoso Fragilizado , Fragilidade/epidemiologia , Infecções por HIV/epidemiologia , Músculo Esquelético/fisiopatologia , Atividades Cotidianas , Fatores Etários , Idoso , Relação CD4-CD8 , Distribuição de Qui-Quadrado , Estudos Transversais , Metabolismo Energético , Exercício Físico , Feminino , Fragilidade/diagnóstico , Fragilidade/fisiopatologia , Avaliação Geriátrica , Infecções por HIV/diagnóstico , Hospitais Públicos , Hospitais Universitários , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Debilidade Muscular , Músculo Esquelético/metabolismo , Razão de Chances , Resistência Física , Prevalência , Fatores de Risco , Espanha/epidemiologiaRESUMO
BACKGROUND AND AIMS: Fibrosis regression (FR) after sustained virological response (SVR) should produce a better outcome in hepatitis C (HCV)-/HIV-coinfected patients with liver cirrhosis, but there are no specific data in this issue. METHODS: We compared the incidence rate (IR) and the time to develop a liver complication and death in 133 cirrhotic patients according to SVR or/and FR. RESULTS: Of 42 patients with SVR, 23 (55%) had FR, in comparison with only 14 of the 91 (15%) without SVR. During a follow-up of 6.8 years (916.8 person-years), the IR of death, liver-related death, and liver-related complications were 2.45, 0.61, and 1.22 per 100 persons/year among SVR/FR, and 7.6, 5.9, and 6.81 among non-SVR without FR (p < 0.01), respectively. SVR patients without FR had also a lower rate of liver-related complications (1.78 vs 3.25; p = 0.02), but a worse IR of death (5.36) and liver-related death (2.68) than non-SVR patients with FR (1.3, and 0.65; p < 0.01). Moreover, FR was associated with less hospital admissions and decreasing alpha-fetoprotein levels. In Cox analysis, only FR was associated with a lower risk of death (adjusted hazard ratio, HR 0.36; 95% CI 0.15-0.86), and liver-related death (HR 0.15; 95% CI 0.03-0.65), whereas both FR (HR 0.09; 95% CI 0.03-0.3, p < 0.01) and SVR (HR 0.24; 95% CI 0.07-0.87) decreased the risk of liver-related complications. CONCLUSION: Fibrosis regression after SVR is associated with the highest reduction in death of any cause, liver-related mortality, and liver-related complications in HIV-/HCV-coinfected patients with cirrhosis.
Assuntos
Antivirais/uso terapêutico , Coinfecção , Infecções por HIV/complicações , Hepatite C/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Adulto , Causas de Morte , Distribuição de Qui-Quadrado , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/mortalidade , Hepatite C/complicações , Hepatite C/diagnóstico , Hepatite C/mortalidade , Humanos , Incidência , Estimativa de Kaplan-Meier , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Indução de Remissão , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVES: To describe raltegravir pharmacokinetics at steady-state in HIV/hepatitis C virus (HCV)-coinfected patients under antiretroviral (ARV) treatment with (nâ=â5) and without (nâ=â5) advanced liver cirrhosis (Child-Pugh C). METHODS: This was a non-randomized, Phase I, parallel-assignment, open-label pharmacokinetic study in HIV/HCV-coinfected patients with Child-Pugh grade C hepatic cirrhosis. We recruited clinically stable HIV/HCV-coinfected adult patients with controlled HIV viraemia (<50 copies/mL) for at least 6 months. Raltegravir (400 mg twice daily) was added under fasting conditions for 5 days to the successful ritonavir-boosted protease inhibitor-based ARV regimen. The trial was registered in the ClinicalTrials.gov database (NCT01289951) (LIVERAL). RESULTS: Raltegravir AUC0-12 and C12 were increased 1.72-fold (90% CI, 1.02 to 2.92) and 6.58-fold (90% CI, 2.92 to14.85), respectively, in patients with advanced liver cirrhosis. No safety issues were identified and raltegravir was well tolerated by all patients. CONCLUSIONS: Raltegravir plasma levels are increased in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child-Pugh C). Despite the higher exposure, raltegravir was safe and well tolerated.
Assuntos
Infecções por HIV/sangue , Inibidores de Integrase de HIV/sangue , Hepatite C/sangue , Cirrose Hepática/sangue , Pirrolidinonas/sangue , Adulto , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Inibidores de Integrase de HIV/farmacocinética , Inibidores de Integrase de HIV/uso terapêutico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Pirrolidinonas/farmacocinética , Pirrolidinonas/uso terapêutico , Raltegravir PotássicoRESUMO
OBJECTIVES: We aimed to evaluate whether virological response to a short course of maraviroc monotherapy could predict HIV-1 tropism. METHODS: A clinical trial was performed in HIV-1 treatment-naive patients infected with R5- or non-R5-tropic virus determined using the Trofile(®) assay, with >1000 HIV-1 RNA copies/mL. Maraviroc was administered for 10 days. Viral load was measured at baseline and days 4, 7, 10 and 28. The main outcome measurement was the decline in HIV-1 RNA at day 10. The trial was registered in the ClinicalTrials.gov database (NCT01060618; TROPISMVC). RESULTS: Forty patients [30 R5 and 10 dual/mixed (D/M)] were recruited. There was a significant decrease in HIV-1 RNA after 10 days of maraviroc treatment in patients with R5-tropic virus (median 1.52 log10 RNA copies/mL; 95% CI 1.23-1.63; Pâ<â0.0001), but also in patients with D/M-tropic virus (median 1.62 log(10) RNA copies/mL; 95% CI 0.33-1.88; Pâ=â0.00024). The difference in the HIV-1 RNA decrease (-0.16 log(10) RNA copies/mL; 95% CI -0.53 to 0.22) was not significant (Pâ=â0.410). A decrease >0.5 log(10) RNA copies/mL was found in 96.3% of patients with R5-tropic virus and in 70% of patients with D/M-tropic virus (Pâ=â0.052). The differences were not significant when a decline of 1 log(10) RNA copies/mL was considered (92.6% versus 70%; Pâ=â0.11). CONCLUSIONS: Treatment-naive patients infected with R5- or D/M-tropic virus have similar virological responses to a short course of maraviroc monotherapy. This clinical test thus cannot be used as a surrogate marker of viral tropism in this population.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Cicloexanos/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Triazóis/uso terapêutico , Tropismo Viral , Adulto , Feminino , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Maraviroc , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
Prolonged time on effective antiretroviral therapy (ART) should be associated with a low incidence of neurocognitive impairment (NCI). We investigated the rate of NCI in 162 largely pretreated patients with HIV RNA suppression according to CNS antiretroviral drug penetration in comparison with 67 patients on their first ART line. Cognitive performance (Trailmaking A, B, Digit Symbol, Grooved Pegboard; demographically adjusted and converted to Z scores, NPZ4) was evaluated, and CNS penetration effectiveness (CPE) ranks of 1 to 4 were assigned and summed per regimen. After a median of 173.2 months on therapy (1,909.3 patients-year), the rate of NCI was similar in both groups (mean NPZ4, -0.24 vs -0.2). Pretreated patients received regimens with a CPE <7 in a large proportion (30 vs 9 %; p < 0.01). Patients in monotherapy had worse NPZ4 score than patients receiving triple therapy (-0.78 vs -0.18; p = 0.02; effect sizes 1.38), and a lower CPE score was observed in patients with a CD4+ count nadir <200 cells/ml with NCI (6.5 vs 7.3, p = 0.04). In the multivariate model, only the lowest CD4+ count and hepatitis C virus coinfection were associated with NPZ4, whereas CPE <7 showed a trend to association (p = 0.06) probably due to patients on monotherapy (estimate -0.33, p < 0.01). In conclusion, the rate of NCI in largely pretreated patients was similar to that observed in patients on their first regimen, and nadir CD4+ count continue to be critical. CNS drug penetration should be considered in cases of high risk for NCI.
Assuntos
Terapia Antirretroviral de Alta Atividade , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/virologia , Cognição/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , PrevalênciaRESUMO
The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed.
Assuntos
Infecções por HIV/complicações , Nefropatias/terapia , Adenina/efeitos adversos , Adenina/análogos & derivados , Adenina/uso terapêutico , Algoritmos , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Biópsia , Doenças Cardiovasculares/complicações , Gerenciamento Clínico , Medicina Baseada em Evidências , Infecções por HIV/tratamento farmacológico , Hepatite Viral Humana/complicações , Hepatite Viral Humana/cirurgia , Humanos , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/complicações , Nefropatias/diagnóstico , Testes de Função Renal , Transplante de Rim , Transplante de Fígado , Ácidos Fosforosos/efeitos adversos , Ácidos Fosforosos/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Encaminhamento e Consulta , Terapia de Substituição Renal , Fatores de RiscoRESUMO
OBJECTIVES: Limited data are available on resistance to etravirine, rilpivirine, darunavir and tipranavir in patients infected with HIV-1 non-B subtypes, in which natural polymorphisms at certain positions could influence the barrier and/or pathways to drug resistance. METHODS: FASTA format sequences from the reverse transcriptase and protease genes recorded within the Spanish Drug Resistance database (ResRIS) were examined. RESULTS: From 8272 genotypes derived from 5930 different HIV-1 patients included in ResRIS, 5276 genotypes had complete treatment information. Overall, 85% were from antiretroviral-experienced subjects and 7.5% belonged to HIV-1 non-B subtypes: CRF02_AG, C, F and G being the most prevalent variants. For etravirine, only G190A was more prevalent in B than non-B subtypes, whereas V90I and V179E were more frequent in non-B than B subtypes. For rilpivirine, V108I and Y188I were more frequent in B than non-B subtypes, whereas V90I was more prevalent in non-B subtypes. Despite these differences, the overall prevalence of resistance did not differ significantly when comparing etravirine or rilpivirine in B versus non-B subtypes (11.3% versus 7.4%, Pâ=â0.13, and 10.5% versus 7.4%, Pâ=â0.23, respectively). Despite more frequent natural polymorphisms in non-B than B subtypes at tipranavir resistance positions, the prevalence of tipranavir resistance was greater in B than non-B subtypes (11% versus 4.3%, Pâ=â0.004), reflecting a greater antiretroviral exposure in the former. Darunavir resistance did not differ significantly when comparing B and non-B subtypes (5.8% versus 5.5%, Pâ=â0.998). CONCLUSIONS: The rate of resistance to the most recently approved protease and non-nucleoside reverse transcriptase inhibitors is low in antiretroviral-experienced patients, regardless of the HIV-1 subtype.
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Fármacos Anti-HIV/farmacologia , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacologia , HIV-1/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Adulto , Feminino , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Masculino , Mutação de Sentido Incorreto , Prevalência , Análise de Sequência de DNA , EspanhaRESUMO
PURPOSE: Etravirine (ETR) has shown a good lipid profile in previous studies. The aim of this study was to determine the virologic, immunologic, and lipid outcome in HIV-infected patients switching to an ETR-based antiretroviral regimen due to intolerance or toxicity. METHODS: Observational cohort study of 125 HIV-infected patients who switched therapy to an ETR-based regimen. The lipid profile, including total triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was compared after 24 weeks. RESULTS: Patients changed from efavirenz (n = 34; 28%) and ritonavir-boosted protease inhibitors (PI/r; 67 cases: 21 atazanavir, 21 lopinavir, 11 fosamprenavir, 14 darunavir). Hyperlipidemia was the cause in only 22 patients (18%). At 24 weeks, a significant decrease was observed in mean TC level (-8%), LDL-C (-8%), TC:HDL ratio (-6%), and TG level (-20%). For patients receiving previously efavirenz, there was a significant reduction in TC (-23 mg/dL; -13%) and LDL-C (-25 mg/dL; -21%) levels and a trend to a better TG level (-38 mg/dL; -21%;P = .06). In the case of prior PI/r therapy, there was also a significant reduction in TC (-14 mg/dL; -6%) and TG levels (-58 mg/dL; -16%), mostly in prior lopinavir- or fosamprenavir-based therapy (TC -15%; TG -53%). Median CD4+ count increased from 513 to 621 cells/µL (P = .03), and there were only 3 cases of virologic failure (2%). CONCLUSIONS: In patients switching to an ETR-containing regimen, there is a significant improvement of lipids and maintenance of immunologic and virologic response. This lipid-lowering effect was irrespective of the presence of previous hyperlipidemia and for patients receiving different antiretroviral drugs.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Lipídeos/sangue , Piridazinas/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Alcinos , Sulfato de Atazanavir , Benzoxazinas/uso terapêutico , Contagem de Linfócito CD4 , Carbamatos/uso terapêutico , Estudos de Coortes , Ciclopropanos , Darunavir , Quimioterapia Combinada , Feminino , Furanos , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , Inibidores da Protease de HIV/uso terapêutico , Humanos , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nitrilas , Oligopeptídeos/uso terapêutico , Organofosfatos/uso terapêutico , Piridinas/uso terapêutico , Pirimidinas , Ritonavir/uso terapêutico , Espanha , Sulfonamidas/uso terapêutico , Resultado do TratamentoRESUMO
This study was designed to investigate the persistence of lipodystrophy (LD)-related social distress and isolation in HIV-infected patients in the current era, according to confirmatory dual energy X-ray absorptiometry (DEXA) measurements. Cross-sectional interview data were collected from 168 HIV-positive adult patients taking more than 2 years of antiretroviral therapy (133 cases with LD diagnosed a mean of 7.2 years before; 35 without LD, controls). Mean time of HIV infection was 16.2 years (2.1-27.3), and the mean time of exposure to highly active antiretroviral therapy of 11.7 years (2.1-21.1). The presence and severity of LD, confirmed by DEXA measurements, correlated with social isolation through a validated scale, including avoidance of social relationships, sex, work, or sport activities. In comparison with control patients, social distress was observed for patients having moderate body changes. The significant correlation between LD and social isolation was irrespective of age, CD4+ count, HIV RNA level, AIDS diagnosis, time of HIV infection, anxiety, or depressive symptoms. These results confirm that patient assessment of LD is correlated with whole-body DEXA scan, and they highlight the role of LD as an independent cause of social isolation even after years of the diagnosis.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Síndrome de Lipodistrofia Associada ao HIV/psicologia , Isolamento Social/psicologia , Absorciometria de Fóton , Adulto , Imagem Corporal/psicologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de VidaRESUMO
People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals.
Assuntos
Coinfecção , Infecções por HIV , Soropositividade para HIV , HIV-1 , Infecções por HTLV-II , Hepatite C , Humanos , Vírus Linfotrópico T Tipo 2 Humano , HIV-1/fisiologia , Provírus , Linfócitos T CD8-Positivos/patologia , Carga Viral , Hepatite C/complicaçõesRESUMO
Statins are relatively safe first-line agents to use in the setting of dyslipidemia associated with immunosuppressive therapy in subjects undergoing liver transplantation, and also in HIV-infected patients with dyslipidemia due to antiretroviral drugs, especially ritonavir-boosted protease inhibitors. Rosuvastatin, a new statin, has demonstrated higher potency than previously released statins and is not extensively metabolized by the liver P450 system; therefore, the probability of deleterious pharmacokinetic interactions with commonly used immunosuppressants and antiretroviral drugs is reduced. We present the first case of severe rhabdomyolysis in a liver transplant patient receiving rosuvastatin for the treatment of immunosuppressive therapy-related grade IV dyslipidemia, an HIV-infected subject on protease inhibitor-sparing HAART, that resolved after rosuvastatin withdrawal, probably related to interactions between calcineurin inhibitors and hepatic rosuvastatin uptake transporters such as organic anion transporting polypeptides (OATPs).
Assuntos
Dislipidemias/tratamento farmacológico , Fluorbenzenos/efeitos adversos , Infecções por HIV/complicações , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Imunossupressores/efeitos adversos , Transplante de Fígado , Pirimidinas/efeitos adversos , Rabdomiólise/induzido quimicamente , Sulfonamidas/efeitos adversos , Adulto , Terapia Antirretroviral de Alta Atividade , Dislipidemias/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Rabdomiólise/diagnóstico , Rosuvastatina Cálcica , Índice de Gravidade de DoençaRESUMO
PURPOSE: There are few data about the safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with very advanced liver disease. METHOD: Prospective study of 60 HIV/HCV coinfected patients who underwent a liver biopsy and received a lopinavir-based regimen. The rate of hepatotoxiciy and plasma trough levels were determined in absence/presence of cirrhosis (25 cases), especially in 11 patients with Child-Pugh stage B-C. RESULTS: Overall, geometric mean level of lopi-navir was 7,109 ng/mL (interquartile range [IQR], 5,163-9,029), without differences according to cirrhosis (7,662; IQR, 5,165-10,442) or not (6,708; IQR, 5,524-8,526; P = .6). In 11 patients with Child-Pugh stage B-C, trough level was 9,640 ng/mL (IQR, 1,620-11,622 ng/mL), but there was a 99% interpatient variability (72 to 13,331 ng/mL). During a follow-up of 195.2 patient-years, there were 7 cases of hepatotox-icity, with an incidence of 3.39 episodes/100 patient-years (2.2 to 7.9). This incidence was higher in patients with Child-Pugh stage B-C (5.43 episodes/100 patient-years). There were no differences in lopinavir trough levels between patients with or without liver toxicity (7,100 vs 7,119 ng/mL; P = .9). CONCLUSION: The risk of lopinavir-associated hepatotoxicity in patients with very advanced liver disease is low. However, lopinavir plasma trough levels are increased, and there is a high interpatient variability.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/farmacocinética , Hepatite C/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Lopinavir/efeitos adversos , Lopinavir/farmacocinética , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , Hepatite C/complicações , Hepatite C/virologia , Humanos , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Lopinavir/administração & dosagem , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
In this pilot program of low-dose computed tomography (LDCT) for the screening of lung cancer (LC) in a targeted population of people with HIV (PWH), its prevalence was 3.6%; the number needed to screen in order to detect one case of lung cancer was 28, clearly outweighing the risks associated with lung cancer screening. While data from additional cohorts with longitudinal measurements are needed, PWH are a target population for lung cancer screening with LDCT.
Assuntos
Infecções por HIV/metabolismo , Neoplasias Pulmonares/diagnóstico , Detecção Precoce de Câncer/métodos , Humanos , Neoplasias Pulmonares/metabolismo , Mortalidade , Estudos Prospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVES: We aimed to assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and factors associated with seropositivity and asymptomatic coronavirus disease 2019 (COVID-19) among people with HIV (PWH). METHODS: This was a cross-sectional study carried out within the cohort of the Spanish HIV Research Network. Participants were consecutive PWH with plasma collected from 1st April to 30th September 2020. We determined SARS-CoV-2 antibodies (Abs) in plasma. Illness severity (NIH criteria) was assessed by a review of medical records and, if needed, participant interviews. Multivariable logistic regression analysis was used to identify predictors of seropositivity among the following variables: sex, age, country of birth, education level, comorbidities (hypertension, chronic heart disease, diabetes mellitus, non-AIDS-related cancer, chronic kidney disease, cirrhosis), route of HIV acquisition, prior AIDS, CD4+ cell count, HIV viral load, nucleoside/nucleotide reverse transcriptase inhibitor (N [t]RTI) backbone, type of third antiretroviral drug, and month of sample collection. RESULTS: Of 1076 PWH (88.0% males, median age 43 years, 97.7% on antiretroviral therapy, median CD4+ 688 cells/mm3, 91.4% undetectable HIV viral load), SARS-CoV-2 Abs were detected in 91 PWH, a seroprevalence of 8.5% (95%CI 6.9-10.3%). Forty-five infections (45.0%) were asymptomatic. Variables independently associated with SARS-CoV-2 seropositivity were birth in Latin American countries versus Spain (adjusted odds ratio (aOR) 2.30, 95%CI 1.41-3.76, p 0.001), and therapy with tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) versus tenofovir alafenamide (TAF)/FTC as the N(t)RTI backbone (aOR 0.49, 95%CI 0.26-0.94, p 0.031). CONCLUSIONS: Many SARS-CoV-2 infections among PWH were asymptomatic, and birth in Latin American countries increased the risk of SARS-CoV-2 seropositivity. Our analysis, adjusted by comorbidities and other variables, suggests that TDF/FTC may prevent SARS-CoV-2 infection among PWH.
Assuntos
Fármacos Anti-HIV , COVID-19 , Infecções por HIV , Adulto , Fármacos Anti-HIV/uso terapêutico , COVID-19/diagnóstico , COVID-19/epidemiologia , Estudos Transversais , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Prevalência , Inibidores da Transcriptase Reversa/uso terapêutico , Estudos Soroepidemiológicos , Espanha/epidemiologia , Tenofovir/uso terapêuticoAssuntos
Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Ritonavir/uso terapêutico , Sulfonamidas/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Darunavir , Esquema de Medicação , Sinergismo Farmacológico , Infecções por HIV/virologia , Humanos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Ritonavir/administração & dosagem , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do TratamentoRESUMO
: Changes in weight and body composition were assessed in long-term suppressed HIV-infected patients switching to dolutegravir/rilpivirine (nâ=â37), and compared with similar patients switching to darunavir/lamivudine (nâ=â17). At month 12, weight significantly increased with dolutegravir/rilpivirine (1.8âkg, IQR -1.2 to 4.1; 2.5%; Pâ=â0.03). A follow-up DXA (median, 16 months) showed similar increases in trunk (7.8%), arms (5.6%), and legs (6.2%) fat mass, without changes in lean mass. Despite lower weight gain (0.70âkg, IQR -0.8 to 4.0, Pâ=â0.28), fat mass increase was similar in the darunavir/lamivudine group. Baseline fat mass and CD4 counts were the only factors explaining fat mass gain.
Assuntos
Adiposidade , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Substituição de Medicamentos , Infecções por HIV/tratamento farmacológico , Aumento de Peso/efeitos dos fármacos , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , Compostos Heterocíclicos com 3 Anéis , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Estudos Prospectivos , Piridonas , RilpivirinaRESUMO
BACKGROUND: Information about incidence, clinical characteristics, and outcomes of HIV-infected individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is scarce. We characterised individuals with COVID-19 among a cohort of HIV-infected adults in Madrid. METHODS: In this observational prospective study, we included all consecutive HIV-infected individuals (aged ≥18 years) who had suspected or confirmed COVID-19 as of April 30, 2020, at the Hospital Universitario Ramón y Cajal (Madrid, Spain). We compared the characteristics of HIV-infected individuals with COVID-19 with a sample of HIV-infected individuals assessed before the COVID-19 pandemic, and described the outcomes of individuals with COVID-19. FINDINGS: 51 HIV-infected individuals were diagnosed with COVID-19 (incidence 1·8%, 95% CI 1·3-2·3). Mean age of patients was 53·3 years (SD 9·5); eight (16%) were women, and 43 (84%) men. 35 (69%) cases of co-infection had laboratory confirmed COVID-19, and 28 (55%) required hospital admission. Age and CD4 cell counts in 51 patients diagnosed with COVID-19 were similar to those in 1288 HIV-infected individuals without; however, 32 (63%) with COVID-19 had at least one comorbidity (mostly hypertension and diabetes) compared with 495 (38%) without COVID-19 (p=0·00059). 37 (73%) patients had received tenofovir before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0·0036); 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0·578). Clinical, analytical, and radiological presentation of COVID-19 in HIV-infected individuals was similar to that described in the general population. Six (12%) individuals were critically ill, two of whom had CD4 counts of less than 200 cells per µL, and two (4%) died. SARS-CoV-2 RT-PCR remained positive after a median of 40 days from symptoms onset in six (32%) individuals, four of whom had severe disease or low nadir CD4 cell counts. INTERPRETATION: HIV-infected individuals should not be considered to be protected from SARS-CoV-2 infection or to have lower risk of severe disease. Generally, they should receive the same treatment approach applied to the general population. FUNDING: None.
Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por HIV/complicações , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/uso terapêutico , Índice de Massa Corporal , Contagem de Linfócito CD4 , COVID-19 , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pandemias , Pneumonia Viral/tratamento farmacológico , Estudos Prospectivos , Espanha/epidemiologia , Tenofovir/uso terapêutico , Adulto JovemRESUMO
INTRODUCTION: An increased incidence of stroke in HIV-infected patients has already been reported, suggesting that HIV infection may be a cerebrovascular risk factor. The objective of this study was to assess temporal trends in the proportion of HIV infection among patients with stroke in Spain. METHODS: Data were obtained from the minimum basic dataset (MBDS) of all patients hospitalized in Spain between 1997 and 2012 with a primary or secondary diagnosis of stroke. The annual proportion of HIV infection and time trends (stratifying by type of stroke and HIV stage) were calculated, and predictors of HIV infection and the social and economic impact of HIV-infected (HIV+) and non-infected (HIV-) patients were analyzed. RESULTS: Of 857,371 patients hospitalized with an incident stroke, 2134 (0.25%) had HIV infection. A 2.5% year-on-year increase (OR 1.025, 95% CI 1.015-1.036, p<0.0001) of the proportion of HIV-infected patients was observed due to an increase in the asymptomatic stage of the infection (per year OR 1.077, 95% CI 1.057-1.097, p<0.0001), as the proportion of patients with AIDS remained stable. Factors independently associated with HIV infection and stroke were active smoking, stimulating drugs and hepatitis C virus (HCV) infection. A higher mortality rate, longer hospital stay and a higher cost per hospitalized patient was observed among HIV+ patients. CONCLUSIONS: From 1997 to 2012, there was an increase in the proportion of HIV infection among patients hospitalized with stroke irrespective of the classical vascular risk factors, reinforcing the role of HIV infection as a cerebrovascular risk factor.