Clinical and virological efficacy of etravirine plus two active Nucleos(t)ide analogs in an heterogeneous HIV-infected population.

UNLABELLED: Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1%) and 77.4% (CI95, 65.0-89.7%), respectively; the rates reached 97.2% (CI95, 95.1-99.3%) and 90.5% (CI95, 81.7-99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01437241.

Association between the IL28B genotype and hepatitis C viral kinetics in the early days of treatment with pegylated interferon plus ribavirin in HIV/HCV co-infected patients with genotype 1 or 4.

OBJECTIVES: To evaluate the effect of the interleukin 28B (IL-28B) genotype on hepatitis C virus (HCV) viral kinetics in the first 4 weeks from start of treatment with pegylated interferon plus ribavirin (PEG-IFN/RBV) in HIV/HCV co-infected patients. METHODS: HIV/HCV co-infected patients naive to PEG-IFN/RBV treatment were enrolled in a prospective study. HCV RNA plasma viral loads were measured at baseline and at weeks 1, 2 and 4 after commencement of treatment. Patients were grouped by HCV genotype (genotype 1/4 versus 3) and by IL-28B genotype (CC versus non-CC). Differences in viral load reduction were evaluated by IL-28B genotype between baseline, week 1, week 2 and week 4. RESULTS: One hundred and nineteen HIV/HCV patients were included in the study. HCV patients with genotype 1/4 and bearing the IL-28 CC genotype showed the greatest reductions in HCV RNA plasma levels between baseline and weeks 1 (B-1), 2 (B-2) and 4 (B-4) than did those with non-CC genotypes (B-1: 1.06 ± 0.89 versus 0.48 ± 0.48 log IU/mL, P = 0.009; B-2: 1.36 ± 0.72 versus 0.77 ± 0.66 log IU/mL, P = 0.01; and B-4: 1.91 ± 0.64 versus 1.38 ± 0.96 log IU/mL, P = 0.03). However, differences between weeks 1 and 2 (W1-2) and between weeks 2 and 4 (W2-4) were not associated with the IL-28B genotype (W1-2: CC 0.48 ± 0.42 versus non-CC 0.38 ± 0.38 log IU/mL, P = 0.62; W2-4: CC 0.32 ± 0.23 versus non-CC 0.39 ± 0.31 log IU/mL, P = 0.67). No differences in decline of HCV RNA viral load were found in HCV genotype 3 patients. CONCLUSIONS: The IL-28B genotype impacts on viral kinetics during the first week of treatment with PEG-IFN/RBV in patients with HCV genotype 1/4.

Prevalence and risk factors for abnormal liver stiffness in HIV-infected patients without viral hepatitis coinfection: role of didanosine.

BACKGROUND: Unexpected cases of severe liver disease in HIV-infected patients have been reported and an association with didanosine (ddI) has been suggested. Transient elastography (TE) might detect patients harbouring such a condition. Our objective was to search for the presence of abnormal liver stiffness (LS) in a cohort of HIV-infected patients without HBV or HCV coinfection and to assess the related factors. METHODS: A cross-sectional prospective study was conducted. LS was assessed by TE in 258 HIV-infected patients without HBV or HCV coinfection and with no evidence of acute hepatotoxicity or other origins of liver disease. LS values > or =7.2 kPa were considered abnormal. Multivariate analyses were performed to identify factors associated with abnormal LS. RESULTS: Abnormal LS was observed in 29 (11.2%) patients. A total of 18 (16.4%) patients previously treated with ddI and 11 (7.4%) of those who never received ddI had LS values > or =7.2 kPa (P=0.02). The prevalence of abnormal LS was higher in patients previously treated with abacavir than in those who had never received abacavir (15 [21.7%] versus 14 [7.4%]; P=0.001). After multivariate analyses, age (adjusted odds ratio [AOR] 1.05, 95% confidence interval [CI] 1.002-1.1; P=0.004) alcohol intake >50 g/day (AOR 7.2, 95% CI 2.6-19.7; P<0.0001), CD4(+) T-cell count <200 cells/ml (AOR 3.4, 95% CI 1.06-11.007; P=0.03), time on ddI treatment (AOR 1.31, 95% CI 1.12-1.52; P=0.001) and previous abacavir exposure (AOR 3.01, 95% CI 1.18-7.67; P=0.02) were independently associated with abnormal LS. CONCLUSIONS: The prevalence of abnormal LS in HIV-infected patients without HBV or HCV coinfection is substantial. Long-term exposure to ddI is a major cause of liver damage in these patients.

Usar rifampicina más pirazinamida en profilaxis antituberculosa no incrementa el riesgo de hepatotoxicidad grave en pacientes infectados por virus de la inmunodeficiencia humana: metaanálisis de ensayos clínicos aleatorizados y controlados / Use of rifampicin plus pyrazinamide for antituberculosis prophylaxis does not increase the risk of severe hepatotoxicity in HIV patients: Meta-analysis of randomized controlled clinical trials

Objetivo Comparar la incidencia de hepatitis grave asociada al tratamiento con rifampicina más pirazinamida (RZ) en tratamiento preventivo de tuberculosis en pacientes infectados por virus de la inmunodeficiencia humana (VIH), con pauta estándar de isoniacida (H) durante 6 (6H) o 12 (12H) meses. Pacientes y métodos Metaanálisis de ensayos clínicos de asignación aleatorizada y controlados, en los que se comparó el régimen RZ con la pauta estándar de tratamiento de la infección latente tuberculosa (6 a 12H) en pacientes infectados por VIH. Se realizó una búsqueda sistemática de la literatura médica desde 1986 hasta diciembre de 2007. Se identificaron 5 ensayos clínicos de asignación aleatorizada y controlados, realizados en España, EE. UU., Haití y Zambia. Se valoró como repuesta binaria la ausencia o presencia de hepatotoxicidad grave, definida como aquella que provocó la muerte del paciente o fue causa de retirada del tratamiento, y se estableció como medida la diferencia de riesgo de (..) (AU)

Objective To compare the incidence of severe hepatitis in HIV-infected patients receiving rifampicin plus pyrazinamide (RZ) for antituberculosis prophylaxis with that of patients receiving a conventional isoniazid-based regime for 6 to 12 months (6–12H).Methods Meta-analysis of randomized controlled trials, in which RZ was compared with 6–12H, the standard regimen for latent tuberculosis infection in HIV-infected patients. A systematic search of studies published between 1986 and 2007 was carried out, and 5 randomized clinical trials conducted in Spain (2), the USA (1), Haiti (1), and Zambia (1) were identified. The absence or presence of severe hepatoxicity, which was defined as toxicity causing the death of the patient or requiring treatment withdrawal, was assessed as a binary response, and the outcome measure was the difference in the risk of hepatotoxicity between patients receiving RZ and those receiving 6–12H (controls).Result sAmong the 5 trials retrieved, 1 was excluded from the final analysis because of incomplete data on the development of hepatotoxicity. A final total of 2657 (..) (AU)

[Use of rifampicin plus pyrazinamide for antituberculosis prophylaxis does not increase the risk of severe hepatotoxicity in HIV patients: meta-analysis of randomized controlled clinical trials]. / Usar rifampicina más pirazinamida en profilaxis antituberculosa no incrementa el riesgo de hepatotoxicidad grave en pacientes infectados por virus de la inmunodeficiencia humana: metaanálisis de ensayos clínicos aleatorizados y controlados.

OBJECTIVE: To compare the incidence of severe hepatitis in HIV-infected patients receiving rifampicin plus pyrazinamide (RZ) for antituberculosis prophylaxis with that of patients receiving a conventional isoniazid-based regime for 6 to 12 months (6-12H). METHODS: Meta-analysis of randomized controlled trials, in which RZ was compared with 6-12H, the standard regimen for latent tuberculosis infection in HIV-infected patients. A systematic search of studies published between 1986 and 2007 was carried out, and 5 randomized clinical trials conducted in Spain (2), the USA (1), Haiti (1), and Zambia (1) were identified. The absence or presence of severe hepatoxicity, which was defined as toxicity causing the death of the patient or requiring treatment withdrawal, was assessed as a binary response, and the outcome measure was the difference in the risk of hepatotoxicity between patients receiving RZ and those receiving 6-12H (controls). RESULTS: Among the 5 trials retrieved, 1 was excluded from the final analysis because of incomplete data on the development of hepatotoxicity. A final total of 2657 patients were included (1324 patients receiving RZ and 1333 receiving 6-12H). The development of severe hepatotoxicity was lower in the RZ group than in the 6-12H group (1.208% vs. 2.851%; P=0.0042, 95% CI: -0.028 to -0.005). The meta-analysis showed no statistical evidence of heterogeneity between the studies or publication bias. The difference in the risk of severe hepatotoxicity favored the RZ regimen in both the fixed effects model (-0.0119, 95% CI: -0.0206 to -0.0033) and random effects model (-0.0147, 95% CI: -0.0289 to -0.0006). CONCLUSIONS: The meta-analysis did not demonstrate an increased risk of severe hepatoxicity in HIV-infected patients receiving tuberculosis prophylaxis with the rifampicin/pyrazinamide combination compared to the conventional 6- or 12-month isoniazid-based regimen.

[Variability in coronary risk assessment in HIV-infected patients]. / Variabilidad en la valoración del riesgo coronario en pacientes infectados por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: Antiretroviral treatment of human immunodeficiency virus (HIV)-infected patients seems to increase the coronary risk (CR) in these patients. Adequate assessment of CR has significant implications for the management of these patients. Our objective was to compare 2 systems for assessing 10-year CR in HIV-infected patients. PATIENTS AND METHOD: CR was calculated in a prospective cohort of 205 HIV-infected patients using Framingham tables and REGICOR adapted tables. Prevalence of cardiovascular risk factors in these patients was evaluated. RESULTS: Mean age (standard deviation) was 41.4 (8.2) years. Most patients were taking antiretrovirals and had a good immunological status. Current smoking was reported by 77.1% of patients, while a history of dyslipidemia, hypertension, or diabetes was found in 29.3%, 7.3%, and 4.9% of patients, respectively. Lipodystrophy was seen in 41% of patients, abdominal obesity in 21.5%, and a sedentary lifestyle in 50.7% Mean values obtained were 6.55 (6.36) in the Framingham scale and 2.85 (2.31) in the REGICOR scale. A 10-year CR greater than 10% was found in 26 patients (12.9%) with the Framingham tables and in 4 patients (2.0%) with the REGICOR tables. The difference between both methods was significant (p < 0.001). CONCLUSIONS: Application of the Framingham tables to our cohort may overestimate the CR. Studies aimed at identifying the most adequate method for measuring CR in HIV-infected patients are required. Until such data are available, estimation of CR in these patients should be taken with caution.

Variabilidad en la valoración del riesgo coronario en pacientes infectados por el virus de la inmunodeficiencia humana / Variability in coronary risk assessment in HIV-infected patients

Fundamento y objetivo: El tratamiento antirretroviral de los pacientes infectados por el virus de la inmunodeficiencia humana (VIH) parece aumentar su riesgo coronario (RC). La correcta valoración de éste tiene importantes implicaciones en el tratamiento de estos pacientes. Nuestro objetivo ha sido comparar 2 sistemas de evaluación del RC a 10 años en pacientes infectados por el VIH. Pacientes y método: Se calculó el RC en una cohorte prospectiva de 205 pacientes infectados por el VIH utilizando las tablas de Framingham y las tablas adaptadas REGICOR. Se evaluó la prevalencia de factores de riesgo cardiovascular de estos pacientes. Resultados: La edad media (desviación estándar) fue de 41,4 (8,2) años. La mayoría de los pacientes tomaba antirretrovirales y tenía buena situación inmunológica. Presentaba tabaquismo activo el 77,1%, antecedentes de dislipemia el 29,3%, de hipertensión el 7,3%, de diabetes el 4,9%, lipodistrofia el 41%, obesidad abdominal el 21,5% y sedentarismo el 50,7%. La valoración media en la escala Framingham fue de 6,55 (6,36) y en la escala REGICOR de 2,85 (2,31). El RC a 10 años fue mayor del 10% en 26 pacientes (12,9%) con las tablas de Framingham y en 4 (2,0%) con las tablas REGICOR. La diferencia entre ambos métodos resultó significativa (p < 0,001). Conclusiones: Aplicar las tablas Framingham en nuestra cohorte podría suponer una sobrestimación del RC. Son necesarios estudios que tengan como objetivo identificar el método más adecuado para medir el RC en pacientes infectados por el VIH. Mientras no dispongamos de estos datos, debemos tomar con precaución la estimación del RC en estos pacientes

Background and objective: Antiretroviral treatment of human immunodeficiency virus (HIV)-infected patients seems to increase the coronary risk (CR) in these patients. Adequate assessment of CR has significant implications for the management of these patients. Our objective was to compare 2 systems for assessing 10-year CR in HIV-infected patients. Patients and method: CR was calculated in a prospective cohort of 205 HIV-infected patients using Framingham tables and REGICOR adapted tables. Prevalence of cardiovascular risk factors in these patients was evaluated. Results: Mean age (standard deviation) was 41.4 (8.2) years. Most patients were taking antiretrovirals and had a good immunological status. Current smoking was reported by 77.1% of patients, while a history of dyslipidemia, hypertension, or diabetes was found in 29.3%, 7.3%, and 4.9% of patients, respectively. Lipodystrophy was seen in 41% of patients, abdominal obesity in 21.5%, and a sedentary lifestyle in 50.7% Mean values obtained were 6.55 (6.36) in the Framingham scale and 2.85 (2.31) in the REGICOR scale. A 10-year CR greater than 10% was found in 26 patients (12.9%) with the Framingham tables and in 4 patients (2.0%) with the REGICOR tables. The difference between both methods was significant (p < 0.001). Conclusions: Application of the Framingham tables to our cohort may overestimate the CR. Studies aimed at identifying the most adequate method for measuring CR in HIV-infected patients are required. Until such data are available, estimation of CR in these patients should be taken with caution

[Malnutrition as a prognostic factor in elderly patients with hip fractures]. / Desnutrición como factor pronóstico en ancianos con fractura de cadera.

BACKGROUND AND OBJECTIVE: Hip fracture occurs frequently in elderly patients, with devastating effects on the quality of life due to the high financial burden and the high mortality rate in patients with this condition. Malnutrition is prevalent in the elderly and it can negatively influence patients' recovery from hip fracture. Our proposal was to assess the relationship between malnutrition and the recovery of patients with hip fracture. PATIENTS AND METHOD: A total of 110 patients with hip fractures who were admitted to the orthopedic unit at the Reina Sofía Hospital were reassessed one year after discharge. A prospective cohort design and logistic regression analysis was used. RESULTS: Mean age was 81.4, and 80% of patients were women. After one year 19.7% of patients had died. A multivariate analysis showed a significant relationship between a poor functional recovery and age (odds ratio [OR] = 1.19), caloric malnutrition (OR = 290), protein malnutrition (OR = 125); and there was a significant relationship between being confined to bed and a worse situation before fracture (OR = 10.02); caloric malnutrition (OR = 9.57) and protein malnutrition (OR = 15.23). CONCLUSIONS: Caloric and protein malnutrition were associated with a worse functional recovery in elderly patients with hip fracture.

Desnutrición como factor pronóstico en ancianos con fractura de cadera / Malnutrition as a prognostic factor in elderly patients with hip fractures

Fundamento y objetivo: La fractura de cadera es una complicación frecuente en los pacientes ancianos, con efectos devastadores sobre la calidad de vida, elevado coste y mortalidad en quienes la presentan. La desnutrición, frecuente en los ancianos, puede influir negativamente en la evolución de estos pacientes con fractura de cadera. El objetivo del trabajo ha sido valorar el papel de la desnutrición en la evolución funcional de estos pacientes. Pacientes y método: De los pacientes ingresados en el Servicio de Traumatología del Hospital Reina Sofía por una fractura de cadera, un total de 110 fueron seguidos durante un año tras el alta, registrándose la situación funcional. Se aplicaron un diseño de cohorte prospectivo y un análisis de regresión logística. Resultados: La edad media fue de 81,4 años y un 80% eran mujeres. Al cabo de un año había fallecido el 19,7%. En el modelo de regresión, mostraron una relación significativa con una peor recuperación funcional la edad (odds ratio [OR] = 1,19), la desnutrición calórica (OR = 290) y la desnutrición proteica (OR = 125), mientras que se asociaron con encamamiento al año la peor situación antes de la fractura (OR = 10,02), la desnutrición calórica (OR = 9,57) y la desnutrición proteica (OR = 15,23). Conclusiones: La desnutrición calórica y proteica se asocia con una peor recuperación funcional de los pacientes ancianos con fractura de cadera

Background and objective: Hip fracture occurs frequently in elderly patients, with devastating effects on the quality of life due to the high financial burden and the high mortality rate in patients with this condition. Malnutrition is prevalent in the elderly and it can negatively influence patients' recovery from hip fracture. Our proposal was to assess the relationship between malnutrition and the recovery of patients with hip fracture. Patients and method: A total of 110 patients with hip fractures who were admitted to the orthopedic unit at the Reina Sofía Hospital were reassessed one year after discharge. A prospective cohort design and logistic regression analysis was used. Results: Mean age was 81.4, and 80% of patientes were women. After one year 19.7% of patients had died. A multivariate analysis showed a significant relationship between a poor functional recovery and age (odds ratio [OR] = 1.19), caloric malnutrition (OR = 290), protein malnutrition (OR = 125); and there was a significant relationship between being confined to bed and a worse situation before fracture (OR = 10.02); caloric malnutrition (OR = 9.57) and protein malnutrition (OR = 15.23). Conclusions: Caloric and protein malnutrition were associated with a worse functional recovery in elderly patients with hip fracture

Efficacy of low-dose boosted saquinavir once daily plus nucleoside reverse transcriptase inhibitors in pregnant HIV-1-infected women with a therapeutic drug monitoring strategy.

The efficacy of low-dose, ritonavir-boosted saquinavir (SQV/rtv) once daily plus 2 nucleoside retrotranscriptase inhibitors (NRTIs) in pregnant human immunodeficiency virus (HIV)-1-infected women was prospectively evaluated, ensuring a SQV minimum concentration (Cmin) >/=100 ng/mL with a therapeutic drug monitoring strategy. The primary clinical endpoint was the percentage of women with an HIV-RNA viral load (VL) of <50 copies/mL at the time of delivery. Forty-nine pregnancy episodes were included, with a median CD4 count and VL of 441/muL and 3710 copies/mL, respectively. Two patients were lost to follow-up and 1 patient discontinued treatment because of abdominal discomfort. SQV levels were in excess of the target Cmin in 43 of 46 episodes (93.4%) in which the end of pregnancy was reached on 1200/100 mg daily. The dosage was increased to 1600/100 mg in the remaining 3 episodes to achieve the target levels. By an intention-to-treat analysis, VL was undetectable at delivery in 43 episodes (87.7%; 95% confidence interval, 78.5-96.9) after a median of 18 weeks of treatment (range, 3-39). In the 3 episodes remaining, VLs of 110,400 copies/mL and no available data were observed after only 3 weeks of treatment. Mild adverse events attributable to SQV/rtv occurred in 6 of 49 pregnancies (12.2%). No cases of HIV vertical transmission were observed. The pharmacokinetics, efficacy, and tolerability of this regimen suggest that once-daily low-dose boosted SQV may be considered an appropriate option in PI-naive or limited-PI-experienced HIV-infected pregnant women. Nevertheless, therapeutic drug monitoring is advisable to maintain appropriate levels throughout pregnancy.

Relationship between 1,25-dihydroxycholecalciferol levels and functional outcome after hip fracture in elderly patients.

A prospective study was performed in 109 patients with osteoporotic hip fracture to verify the relationship between 1,25-dihydroxycholecalciferol levels at admission and functional recovery in elderly patients with hip fracture. 47.7% of all the patients had 1,25-dihydroxycholecalciferol levels below the reference values of our laboratory. At 1 year of the fracture only 33 patients (30.3%) had recovered the functional level they had before the fracture. In the bivariate analysis, a statistically significant relationship was found between reduced 1,25-dihydroxycholecalciferol levels and a poorer functional recovery 1 year after the fracture was sustained. A multivariate analysis showed a significant relationship between 1,25-dihydroxycholecalciferol levels and absolute dependence of the patient 1 year after the fracture (P = 0.005; OR 6.97: CI- 1.77-27.41).

Low incidence of severe liver events in HIV patients with and without hepatitis C or B coinfection receiving lopinavir/ritonavir.

OBJECTIVES: To analyze the incidence of severe liver events in HIV patients treated with lopinavir/ritonavir and the role of coinfection in the development of this toxicity. METHOD: This was a retrospective, multicenter, cohort study of all HIV-positive patients who started a regimen of HAART that included lopinavir/ritonavir (LPV/r). The main outcome variable was the emergence of a severe liver event, defined as decompensation of pre-existing chronic liver disease and grade 3-4 hypertransaminasemia (HT), that is, plasma AST or ALT values >5 times above the upper limit of normality, if baseline levels were normal, or >3.5 times the baseline values when they were abnormal. RESULTS: 388 HIV-infected patients were included, with a median follow-up of 25.6 months. Coinfection with HCV was present in 61% of the patients and with HBV in 6.7%. There were 6 cases of severe liver events, all involving patients who were coinfected with HCV and all within the first 6 months. This represents 0.72 events per 100 patient-years (95% confidence interval [CI] 0.36-2.98) and 1.21 events per 100 patient-years (95% CI 0.60-5.86) in coinfected patients. The only factors associated with severe liver events at 6 months were baseline HT and HCV coinfection. CONCLUSION: The incidence of severe hepatic events in HIV-positive patients receiving a HAART regimen including LPV/r was very low, even in coinfected patients. HCV coinfection and baseline HT were the only factors associated with severe liver events. LPV/r can be considered a safe and well-tolerated option in HIV patients with hepatotropic virus coinfections.