Switching from tenofovir containing regimens to boosted protease inhibitor monotherapy: Impact on renal function / Simplificación a monoterapia con inhibidores de la proteasa potenciados desde regímenes con tenofovir: impacto en la función renal

OBJECTIVE: To evaluate the effect on creatinine clearance (CG-CrCl, Cockcroft-Gault equation) of switching to boosted protease inhibitor (PI) monotherapy in patients receiving a triple drug antiretroviral regimen containing TDF. METHODS: All patients who had received a TDF-containing regimen for at least one year and had been switched to PI monotherapy were included. A rapid decrease in CG-CrCl during exposure to TDF was defined as a decrease in CG-CrCl at least five times higher than the expected due to age (0.4 ml/min/year by the years of exposure to TDF). In this subgroup of patients, we considered improvement if the last value of CG-CrCl on PI monotherapy was 10% higher than the last value of CG-CrCl before switching to PI monotherapy. A multivariate logistic regression was constructed to identify factors associated to renal improvement after switching to bPI monotherapy. RESULTS: 64 patients included. The median (IQR) annual change in CG-CrCl during PI monotherapy was significantly lower than the median (IQR) annual change while exposed to TDF [−0.9 (−4.7 to +2.8) ml/min vs. −4 (−8 to −1) ml/min, p = 0.001]. 44 patients experienced a rapid decline during TDF exposition. After switch to PI monotherapy, 15/44 (34%, 95% CI: 21-50%) had an improved CG-CrCl and 16/44 (36%, CI 23-52%) experienced a further decline in CG-CrCl. The only variable associated to CG-CrCl improvement was a more rapid CG-CrCl decline in the last year of exposure to TDF. CONCLUSION: Switching to PI monotherapy partially reversed CG-CrCl decrease associated to TDF use, especially in patients with a more rapid decline while receiving TDF

OBJETIVO: Evaluar el efecto de la retirada de TDF en el aclaramiento de creatinina medido mediante la fórmula de Cockcroft-Gault (CG-ClCr) en pacientes que simplifican a monoterapia con un inhibidor de la proteasa (IP) potenciado. MÉTODOS: Se incluyeron todos los pacientes que habían recibido un regimen con TDF durante al menos un año y que posteriormente habían sido simplificados a monoterapia. Se definió como rápida disminución del CG-CrCl durante la exposición a TDF a una disminución del CG-CrCl de al menos 5 veces mayor de lo esperado para la edad (0.4 ml/min/año por los años de exposición al TDF). En este subgrupo de pacientes, se consideró mejoría si el último valor del CG-CrCl durante la exposición a monoterapia era un 10% más alto que el último valor de CG-CrCl antes de la simplificación. Se construyó una regresión logística multivariante para identificar los factores asociados a mejoría del CG-ClCr. RESULTADOS: Se incluyeron 64 pacientes. La mediana del cambio anual en el CG-CrCl durante la exposición a monoterapia fue significativamente inferior a la mediana del cambio anual durante la exposición a TDF (p = 0.001). 44 pacientes presentaron una rápida disminución del CG-CrCl durante la exposición a TDF. Después de la simplificación, 15/44 (34%, IC 95%: 21-50%) presentaron una mejoría del CG-CrCl y 16/44 (36%, IC 23-52%) continuaron con un empeoramiento en el CG-CrCl. La única variable asociada con mejoría fue haber presentado una disminución más rápida del CG-CrCl en el último año de exposición a TDF. CONCLUSIÓN: La simplificación a monoterapia revierte parcialmente la disminución del CG-CrCl asociada al TDF, especialmente en los pacientes que presentan una disminución más rápida durante la exposición a TDF

Switching from tenofovir containing regimens to boosted protease inhibitor monotherapy: Impact on renal function.

OBJECTIVE: To evaluate the effect on creatinine clearance (CG-CrCl, Cockcroft-Gault equation) of switching to boosted protease inhibitor (PI) monotherapy in patients receiving a triple drug antiretroviral regimen containing TDF. METHODS: All patients who had received a TDF-containing regimen for at least one year and had been switched to PI monotherapy were included. A rapid decrease in CG-CrCl during exposure to TDF was defined as a decrease in CG-CrCl at least five times higher than the expected due to age (0.4ml/min/year by the years of exposure to TDF). In this subgroup of patients, we considered improvement if the last value of CG-CrCl on PI monotherapy was 10% higher than the last value of CG-CrCl before switching to PI monotherapy. A multivariate logistic regression was constructed to identify factors associated to renal improvement after switching to bPI monotherapy. RESULTS: 64 patients included. The median (IQR) annual change in CG-CrCl during PI monotherapy was significantly lower than the median (IQR) annual change while exposed to TDF [-0.9 (-4.7 to +2.8) ml/min vs. -4 (-8 to -1) ml/min, p=0.001]. 44 patients experienced a rapid decline during TDF exposition. After switch to PI monotherapy, 15/44 (34%, 95% CI: 21-50%) had an improved CG-CrCl and 16/44 (36%, CI 23-52%) experienced a further decline in CG-CrCl. The only variable associated to CG-CrCl improvement was a more rapid CG-CrCl decline in the last year of exposure to TDF. CONCLUSION: Switching to PI monotherapy partially reversed CG-CrCl decrease associated to TDF use, especially in patients with a more rapid decline while receiving TDF.

A prospective cohort study of neurocognitive function in aviremic HIV-infected patients treated with 1 or 3 antiretrovirals.

BACKGROUND: The evolution of neurocognitive performance in aviremic human immunodeficiency virus (HIV)-positive patients treated with <3 antiretrovirals is unknown. METHODS: We prospectively included aviremic (≥1 year) HIV-positive patients, without concomitant major neurocognitive confounders, currently receiving boosted lopinavir or darunavir as monotherapy (n = 67) or triple antiretroviral therapy (ART) (n = 67) for ≥1 year. We evaluated neurocognitive function (7 domains) at baseline and after 1 year. We performed analysis of covariance to evaluate if 1 additional year of exposure to monotherapy compared with triple ART had an effect on Global Deficit Score (GDS) changes after adjustment for potential confounders. We also compared the evolution of neurocognitive performance and impairment rates. RESULTS: Intention-to-treat analysis showed that monotherapy did not influence 1-year GDS change after adjustment for significant confounders (age, ethnicity, duration of therapy, hepatitis C virus status, and HOMA-IR index); the adjusted effect was -0.04 (95% confidence interval, -.14 to .05; P = .38). Neurocognitive stability was observed with monotherapy and triple therapy (GDS crude mean change, -0.09 [95% confidence interval, -.16 to -.01] vs -0.08 [-.14 to -.02]), after 1 year of follow-up, similar proportions of patients changed neurocognitive status from impaired to unimpaired (monotherapy, 4 of 18 [22.2%]; triple therapy, 4 of 19 [21.1%]; P = .91) and vice versa (monotherapy, 5 of 44 [10.2%] and triple therapy, 3 of 45 [6.3%]; P = .48). Similar results were observed in an on-treatment analysis and with use of clinical ratings instead of GDS changes. CONCLUSIONS: The number of antiretrovirals included in the ART regimen does not seem to influence the evolution of neurocognitive function in HIV-infected patients with suppressed plasma viremia.

Neurocognitive impairment in patients treated with protease inhibitor monotherapy or triple drug antiretroviral therapy.

BACKGROUND: In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment. METHODS: In this observational, cross-sectional study we included patients with plasma virological suppression (≥ 1 year) without concomitant major neurocognitive confounders, currently receiving for ≥ 1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed. RESULTS: Of the 191 included patients--triple therapy: 96, 1-2 years of monotherapy: 40 and >2 years of monotherapy: 55--proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9-33.6); triple therapy, 31.6% (22.1-41.0); short-term monotherapy, 25.0% (11.3-38.7); long-term monotherapy: 21.4% (10.5-32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29-2.50) and for long-term monotherapy 0.40 (0.14-1.15). CONCLUSIONS: Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.

Transient elastography to rule out esophageal varices and portal hypertensive gastropathy in HIV-infected individuals with liver cirrhosis.

BACKGROUND/AIMS: It is recommended that patients with cirrhosis undergo endoscopic screening to rule out the presence of gastroesophageal varices: a noninvasive predictive method to identify cirrhotic patients with a very low risk of esophageal varices could potentially avoid unnecessary endoscopies. METHODS: We studied in 85 HIV-infected patients with cirrhosis the association between the absence of esophageal varices and portal hypertensive gastropathy, assessed by endoscopy, and liver stiffness measurement by transient elastography. We analyzed other parameters related to portal hypertension and hepatic function. RESULTS: Values of transient elastography and platelet count were significantly associated with absence of esophageal varices/portal hypertensive gastropathy. The area under the receiver operating characteristics curve [95% confidence interval (CI)] of transient elastography for the prediction of the absence of esophageal varices/portal hypertensive gastropathy was 0.7 (0.58-0.81). A liver stiffness measurement value less than 20 kPa was highly predictive of the absence of esophageal varices and portal hypertensive gastropathy. The combination of transient elastography (<20 kPa) and platelet count (>120 × 10 cells/l) had the highest negative predictive value (100%, CI 95% 77.2-100) for absence of esophageal varices and portal hypertensive gastropathy. CONCLUSION: Transient elastography combined with platelet count is useful for predicting the absence of esophageal varices and portal hypertensive gastropathy and, therefore, avoid unnecessary diagnostic endoscopies in HIV-infected patients with liver cirrhosis.