ABSTRACT
OBJECTIVES: The aim of this study was to determine the evolution of renal function in patients receiving one or two inhibitors, according to different baseline factors. Some antiretroviral drugs such as rilpivirine (RPV), dolutegravir (DTG), or cobicistat (COBI), interact with the tubular secretion of creatinine, but there are no data about their impact in renal function evaluation in patients with renal disease or when these drugs are used concomitantly. METHODS: A prospective cohort study was carried out in HIV-infected patients who switched to a dual regimen including DTG, RPV or darunavir/COBI, separately or in combination. The primary endpoint was the evolution of the serum creatinine-based estimated glomerular filtration rate (eGFR-scr). A control group not receiving any transporter inhibitor was included. RESULTS: A total of 288 patients on different dual regimens were included (DTG + RPV, 92; DTG + darunavir/COBI, 23; DTG, 26; COBI, 19; control group, 128). In patients receiving two transporter inhibitors, eGFR-scr decreased by a mean of -8.4 mL/min/1.73 m2 , similar to that observed with the separate use of DTG or COBI (mean of both groups, -8.6 mL/min/1.73 m2 ), while eGFR-scr improved in the control group. Similar evolution of proteinuria and tubular dysfunction was observed in all the groups, and there were no significant changes in the cystatin C-based eGFR. Mean eGFR-scr change inversely correlated with baseline eGFR-scr value (r = -0.39; P < 0.01), with a lower eGFR-scr decrease in patients with chronic kidney disease. CONCLUSIONS: Similar eGFR-scr decreases were observed in patients using different antiretroviral drugs inhibiting the tubular transport of creatinine, separately or in combination, with no alterations in proteinuria or cystatin C-based eGFR. The lack of additional changes when the drugs were used in combination, and the lower impact in cases of previous chronic kidney disease, suggest that there are compensatory mechanisms for creatinine secretion.
Subject(s)
Anti-Retroviral Agents/adverse effects , Creatinine/blood , Darunavir/adverse effects , HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , Heterocyclic Compounds, 3-Ring/adverse effects , Kidney Diseases/chemically induced , Rilpivirine/adverse effects , Adult , Anti-Retroviral Agents/therapeutic use , Case-Control Studies , Female , Glomerular Filtration Rate , Humans , Kidney Diseases/blood , Male , Middle Aged , Oxazines , Piperazines , Prospective Studies , PyridonesABSTRACT
OBJECTIVES: We investigated the reversibility of tenofovir disoproxil fumarate (TDF)-associated renal decline and tubular dysfunction using different antiretroviral strategies. METHODS: A successive evaluation of renal [estimated glomerular filtration rate (eGFR)] and tubular (phosphataemia, proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria and tubular proteinuria) parameters was performed in 231 patients, before and after switching from TDF to abacavir (n = 60), using dual therapy (n = 49), or continuing the same regimen including TDF (n = 122). RESULTS: In a successive evaluation after a median of 8.86 months, or less time if treatment was switched (4.8 months vs. 13.3 months to second evaluation; P < 0.01), a significant improvement in eGFR (median change +0.3 vs. -2.91 mL/min/1.73 m2 in patients who did not discontinue TDF; P = 0.04) and tubular dysfunction (median change -40% vs. +30%, respectively; P < 0.01) was observed. Lineal regression showed that age (ß = -0.14; P = 0.04), previous eGFR decline (ß = -0.42; P < 0.01), and time on TDF (ß = -0.19; P = 0.04) were associated with impaired eGFR recovery. There were no differences in eGFR slopes between patients using abacavir instead of TDF and those using a dual therapy, who showed similar improvement in proteinuria (-22% vs. -19%, respectively), phosphaturia (+10.1% vs. +9.4%, respectively), and urinary beta-2-microglobulin (-9% vs. -15%, respectively; P > 0.1 for all), although patients receiving the dual regimen were more heavily pretreated. A eGFR decrease (-6.17 mL/min/1.73 m2 ) was observed in patients taking dolutegravir or rilpivirine, but with similar improvement to that observed in the rest of switching patients in tubular abnormalities. CONCLUSIONS: Tenofovir disoproxil fumarate discontinuation was associated with a rapid and significant improvement in eGFR and tubular abnormalities, regardless of whether abacavir or dual therapy was chosen. Switching to a regimen that included dolutegravir and/or rilpivirine was associated with a eGFR decrease without differences in the rate of tubular dysfunction improvement in comparison with the rest of patients who discontinued tenofovir.
ABSTRACT
El Ministerio de Salud, a través del Programa Remediar y con la participación de 24 Facultades de Medicina, implementa un Programa de Capacitación en Terapéutica Racional de Atención Primaria de la Salud (TRAPS) destinado a médicos/as que se desempeñan en el primer nivel de atención (PNA). En el Curso sobre Riesgo Cardiovascular Global (RCVG) se promueve la utilización de la Guía de la OMS adaptada para Argentina para la estimación del riesgo. Objetivo. Presentar los resultados de un estudio cualitativo que indaga, entre los profesionales que habían asistido al curso, el conocimiento y la utilización de la Guía. Material y Método. Población: médicos/as que se desempeñan en Centros de Salud en las provincias de Catamarca y La Rioja...
The Ministry of Health, through a Program called Remediar and with the participationof 24 Schools of Medicine, is implementing a Training Program on Rational Therapeuticsin Primary Health Care intended for doctors working in the fi rst level of care. In theCourse on Absolute Cardiovascular Disease Risk (ACVDR), the use of WHO Guidelinesfor the Assessment of Risk adapted for Argentina is promoted.Objective: To present the results of a qualitative study enquiring professionals who attendedthe course, regarding the knowledge and use of the Guidelines.Material and Method: Semi-structured deep interviews to explore dimensions such as patient-doctorrelationship, the approach to people with cardiovascular disease risk and thefactors involved in the process of patient care.Population: Doctors who work in Health Centers in the provinces of Catamarca and LaRioja and took the course on ACVDR.Results: Interviews took place between...
O Ministério da Saúde, por meio do Programa Remediar e com a participação de 24Faculdades de Medicina, implementa um Programa de Treinamento sobre Terapêutica Racionalde CuIdados Primários da Saúde (TRAPS) para médicos as que servem no primeiro nível de cuidados (PNA). No curso sobre Risco Cardiovascular Global (RCVG) é promovidaa utilização do Guia da OMS adaptado para a Argentina para a estimativa de risco.Escopo: Apresentar os resultados de um estudo qualitativo que questiona, entre os profi ssionaisque participaram do curso, sobre o conhecimento e o uso do Guia.Material e métodos: Entrevistas em profundidade semi-estruturadas, através das quais sãopesquisadas as dimensões, tais como relação médico-paciente, a abordagem de pessoascom risco cardiovascular e dos fatores institucionais envolvidos no processo dos cuidadosPopulação: Médicos que trabalham em centros de saúde nas províncias de Catamarca e LaRioja, e que fi zeram o curso em RCVG...
