Enrique Ortega

Consorcio Hospital General Universitario de Valencia, Valenza, Valencia, Spain

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Publications (38)239.64 Total impact

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    ABSTRACT: Introduction In general, HIV co-infected patients included in clinical trials evaluating the hepatitis C virus (HCV) therapy with telaprevir (TVR) or boceprevir (BOC) with advanced fibrosis, are scarce. We analyze data concerning the use of these drugs in a real-life clinical setting with patients affected by a more advanced degree of fibrosis in a Spanish cohort. Methods We evaluated safety and efficacy in an interim analysis encompassing the first 24 weeks of triple therapy with peginterferon (alfa-2a or alfa-2b), ribavirin and TVR or BOC in an observational, multicentre study. HIV/HCV genotype 1 co-infected patients beginning therapy from January 2012 to July 2013 were included. Results Enrolled patients were 155 (144 patients on TVR and 11 on BOC), average age was 47 years, 83% were male. With respect to HCV treatment, 44% were naïve, 13% relapsers, 17% partial responders, 21% null responders, and in seven patients, the previous response was unknown. All but three (98%) were under antiretroviral therapy (ART) (other than reverse transcriptase inhibitors, the backbone was raltegravir 43%, atazanavir 35%, and etravirine 28%). Median HCV-RNA at baseline was 6.1 log10, 54% were cirrhotic and 38% F3. At week 4, 93% of patients continued on therapy, 81% at w12, and 73% at w24. Virological failure was observed more frequently in: cirrhotic patients (19% [95% CI, 11–27]) vs F3 (12% [CI, 4–20]); patients with TT allele of the IL28B polymorphism (40% [CI, 18–61]) vs CT (21% [CI, 12–31]), or CC (2,2% [CI, −2–6]); previous null responders (37.5% [CI, 21–54]) vs partial responders (15.4% [CI, 1–29]), naïve (13% [CI, 5–21]) or relapsers (0% [CI, 0–0]); and in patients with a genotype subtype 1a (23.6% [CI, 57–76]) vs 1b (8.1% [CI, −1–17]). Overall, 17% had virological failure and in 8% treatment was discontinued due to adverse events. Severe adverse events occurred in 30 patients (19%). Haematologic disorders were the most common type including severe anaemia in 12 (7.7%) patients. Erythropoietin was employed in 41 patients (26.4%) and 11 (7.1%) received blood transfusions. Nineteen patients (12.2%) were treated with G-CSF, and 17 (11%) with thrombopoietin-receptor agonists. Five patients died (3.2%), three due to hepatic decompensation, one due to pneumonia and one due to pulmonary hypertension. Conclusions In a real-life setting, therapy against HCV in co-infected patients with advanced liver fibrosis shows high virologic success at 24 weeks. However, frequent haematologic disorders are observed and a close monitoring and an intensive therapy are needed to optimize the results.
    Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19634. DOI:10.7448/IAS.17.4.19634 · 4.21 Impact Factor
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    ABSTRACT: This study assesses the incidence of hepatocellular carcinoma (HCC) in a prospective cohort of HIV-infected patients, the majority receiving antiretroviral therapy, with liver cirrhosis from different etiologies, enrolled between 2004 and 2005 with median follow-up of 5 years. We followed 371 patients, 25.6% with decompensated cirrhosis at baseline. The incidence rate of HCC was 6.72 per 1000 person-years [95% confidence interval (CI): 2.6 to 10.9]. There was a trend toward a higher cumulative probability of developing HCC at 6 years of follow-up (considering death and liver transplant as competing risks) in patients with decompensated versus compensated cirrhosis at baseline (6% vs. 2%, P < 0.06).
    JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2014; 65(1):82-86. DOI:10.1097/QAI.0b013e3182a685dc · 4.39 Impact Factor
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    ABSTRACT: Background. Most HIV/HCV-infected patients who are currently receiving boceprevir or telaprevir-based therapy against HCV show cirrhosis. However, the risk of liver decompensations (DC) among HIV/HCV-coinfected patients with stage F3 in the short-term could be high enough to not allow delays. We aimed at assessing the risk of DC among HIV/HCV-coinfected individuals with advanced fibrosis (F3-F4). Methods. 892 HIV/HCV-coinfected patients, naïve or without SVR to HCV therapy, were included in this cohort. Fibrosis was staged by biopsy in 317 patients and by liver stiffness measurement (LSM) in 575 individuals. LSM 9.5-14.6 KPa was defined as precirrhosis, and ≥14.6 KPa as cirrhosis. Results. For patients with biopsy, the probability of remaining free of DC for F3 vs. F4 was: at 1 year, 99% (95%-100%) vs. 96% (91%-98%); at 3 years, 98% (94%-100%) vs. 87% (81%-92%). The only factor independently associated with DC was fibrosis stage (F4 vs. F3, subhazard ratio [SHR] 2.1; 95%CI, 1.07-4.1; p=0.032). For patients with LSM, the probability of remaining free of DC for precirrhosis vs. cirrhosis was: at 1 year, 99% (96%-100%) vs. 93% (89%-96%); at 3 years, 97% (94%-99%) vs. 83% (77%-87%). Factors independently associated with DC were platelet count (<100x10(3) vs. ≥100x10(3), SHR 1.86; 95%CI, 1.01-3.42; p=0.046) and LSM (cirrhosis vs. precirrhosis, SHR 5.67 (95%CI, 2.27-14.1; p<0.0001). Conclusions. As in patients with cirrhosis, immediate therapy against HCV is warranted for patients with precirrhosis and HIV coinfection, as they are at risk of DC soon after the diagnosis of advanced fibrosis.
    Clinical Infectious Diseases 08/2013; 57(10). DOI:10.1093/cid/cit537 · 9.42 Impact Factor
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    ABSTRACT: OBJECTIVE:: To compare the prognostic performance of liver biopsy (LB)with that of liver stiffness measurement (LSM) to predict survival and liver decompensations among HIV/HCV-coinfected patients. DESIGN:: Retrospective cohort study. METHODS:: Cohort of 297 HIV/HCV-coinfected patients, who underwent aLB and LSM separated by 12 months or less, followed in ten Spanish tertiary care centers from December 2005 to December 2011 (median follow-up, 5 years; interquartile range, 4.2-5.4 years). LB were staged following the Scheuer's score. LSM was obtained by hepatic transient elastometry. A survival analysis was carried out and the integrated discrimination improvement was computed to compare the ability of the survival models to predict outcomes. The incidence of death from any cause and of development of the first decompensation of cirrhosis were calculated. RESULTS:: Overall mortality rate was 1.63 (95%CI: 1.06-2.49) per 100 person-years. The adjusted hazard ratio [AHR (95%CI)] of baseline fibrosis (per stage of fibrosis) was 1.52 (1.08-2.15, p = 0.017) and of LSM (per 5 KPa increase) 1.28 (1.12-1.46, p < 0.001). LMS including models yielded a performance 3.9% better than the LB-based models (p = 0.072). For the prediction of liver decompensations, the AHR (95%CI) of baseline fibrosis by LB (per stage of fibrosis) was 1.67 (1.15-2.43, p = 0.007) and of LSM (per 5 KPa increase) 1.37 (1.21-1.54, p < 0.001). LMS-based models yielded a performance 8.4% better than the LB-based models (p = 0.045). CONCLUSION:: LSM-based prediction achieves a similar yield than LB-based models to predict overall mortality in HIV/HCV-coinfected patients. Models including LSM couldpredict better liver decompensations than LB.
    AIDS (London, England) 06/2013; DOI:10.1097/QAD.0b013e32836381f3 · 6.56 Impact Factor
  • Journal of Hepatology 04/2013; 58:S9. DOI:10.1016/S0168-8278(13)60022-7 · 10.40 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: Sustained viral response (SVR) after therapy with interferon-ribavirin (IF-RB) reduces liver-related (LR) complications and mortality in HIV/HCV-coinfected patients. Here, we assess the impact of end-of-treatment response with subsequent relapse (REL) on LR events (LR death, liver decompensation, hepatocellular carcinoma, or liver transplantation), and liver stiffness (LS) by transient elastography. METHODS: We analyzed the GESIDA 3603 Cohort (HIV/HCV-coinfected patients treated with IF-RB in 19 centers in Spain). Response to IF-RB was categorized as SVR, REL, and no response (NR). The study started when IF-RB was stopped and ended at death or the last follow-up visit. Multivariate regression analyses were adjusted for age, sex, HIV category of transmission, CDC clinical category, nadir CD4+ cell count, HCV genotype, HCV RNA viral load, and liver fibrosis. RESULTS: Of 1599 patients included response was categorized as NR in 765, REL in 250 and SVR in 584. Median follow-up was more than 4 years in each group. Taking the group of patients with NR as reference, we found that the adjusted hazard ratio (95% confidence interval) of liver-related events (liver-related death, liver decompensation, hepatocellular carcinoma, liver transplantation) for patients with REL and for patients with SVR were 0.17 (0.05; 0.50) and 0.03 (0; 0.20), respectively. We also found that SVR was followed by less liver stiffness than both REL and NR. However, REL was associated with less liver stiffness than NR. CONCLUSIONS: Best outcomes were achieved with an SVR. However, REL was associated with less LR mortality, decompensation, and liver stiffness than NR.
    Journal of Hepatology 02/2013; DOI:10.1016/j.jhep.2013.01.042 · 10.40 Impact Factor
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    ABSTRACT: Hepatic steatosis (HS) is frequent in human immunodeficiency virus (HIV)- and hepatitis C virus (HCV)-coinfected patients. Antiretroviral therapy (ART) and metabolic alterations could induce HS. However, a protective effect of ART has been reported in a paired biopsy study. Thus, our aim was to examine the changes and predictors of HS progression among HIV/HCV-coinfected patients with sequential biopsies. We also evaluated the rates of steatohepatitis and factors associated thereof. HIV-infected patients with detectable serum HCV RNA, who underwent two biopsies, separated at least by 1 year, were included in this retrospective study. HS progression was defined as increase in one or more HS grades. The median (interquartile range) time between biopsies was 3.3 (2.0-5.2) years. Among 146 individuals, HS at baseline was observed in 86 (60%) patients and in 113 (77%) in the follow-up biopsy (P < 0.001). Progression of HS was observed in 60 (40%) patients. HS regressed in 11 (8%) patients. Factors associated with HS progression were changes in fasting plasma glucose (FPG) between biopsies (per 10 mg/dL increase; odds ratio [OR] [95% confidence interval; CI] = 1.4 [1.04-1.8]; P = 0.024) and cumulative use of dideoxynucleoside analogs (per year; OR [95% CI] = 1.5 [1.2-1.8]; P = 0.001). Persistent steatohepatitis or progression to steatohepatitis between biopsies was observed in 27 (18%) patients. Persistence of or progression to steatohepatitis was associated with progression ≥1 fibrosis stages between biopsies (OR [95% CI] = 2.4 [1.01-5.7]; P = 0.047). Conclusions: HS progresses frequently and regression is rarely observed in HIV/HCV-coinfected patients, including in those on ART. Cumulative exposure to dideoxynucleoside analogs and increases in FPG are related with HS progression. Stetatohepatitis is frequently observed in these patients and is linked to fibrosis progression. (HEPATOLOGY 2012).
    Hepatology 10/2012; 56(4):1261-70. DOI:10.1002/hep.25791 · 11.19 Impact Factor
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    ABSTRACT: Background. To report the clinical and epidemiological characteristics of hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency virus (HIV)-infected patients in Spain.Methods. All HIV-infected patients diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included. The main characteristics of HCC cases are described and comparisons between cases according to the year of diagnosis are presented.Results. Eighty-two cases of HCC in HIV-infected patients were included, all of them related to viral hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC was diagnosed, a progressive increment in the incidence of HCC in the cohort has occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009. Death occurred in 65 patients (79%), with a median survival of 91 days (interquartile range, 31-227 days). Three of 11 patients (28%) who received potentially curative therapy died, compared with 62 of 71 patients (87%) who did not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed before 2005, cases diagnosed later did not show a higher survival rate.Conclusions. HCC is an emerging complication of cirrhosis in HIV-infected patients. A sharp increase in its incidence has occurred in those also infected by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high, with no significant changes in recent years. Earlier diagnosis, which may allow potentially curative therapy, is necessary.
    Clinical Infectious Diseases 09/2012; 56(1). DOI:10.1093/cid/cis777 · 9.42 Impact Factor
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    ABSTRACT: IntroductionThe assessment of liver fibrosis is crucial for taking therapeutic decisions in patients infected with HIV/AIDS coinfected with HCV, because it allows the prognosis of the disease and the prioritization of hepatitis C treatment in these patients.MethodsA discrete events model simulation (DEMS) and a Markov model have been developed to represent the evolution of liver fibrosis to cirrhosis in patients coinfected with HIV/HVC. The model evaluated two alternatives for the diagnosis and monitoring of these patients, transient elastography performed annually and liver biopsy performed every seven years. The models have been developed under Health Care System perspective and only considered direct medical costs (disease treatment and health state costs). One-way sensitivity analyses were carried out to assess the impact of parameters with higher uncertainty. A discount rate of 3% was applied.ResultsBase case analysis shows that the diagnosis and monitoring of patients with transient elastography is a dominant strategy compared with to liver biopsy, resulting in greater life expectancy at lower cost. The sensitivity analysis performed confirmed the robustness of these results.Conclusion Transient elastography has proved to be a dominant strategy compared to liver biopsy in the diagnosis and monitoring of liver fibrosis in patients coinfected with HIV/HCV in Spain.
    Enfermedades Infecciosas y Microbiología Clínica 06/2012; 30(6):294–299. DOI:10.1016/j.eimc.2011.11.004 · 1.88 Impact Factor
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    ABSTRACT: Sustained virological response (SVR) after therapy with interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). We assessed the effect of SVR on HIV progression and mortality not related to liver disease. An observational cohort study including consecutive HIV/HCV-coinfected patients treated with interferon plus ribavirin between 2000 and 2008 in 19 centers in Spain. Of 1599 patients, 626 (39%) had an SVR. After a median follow-up of approximately 5 years, we confirmed that failure to achieve an SVR was associated with an increased risk of liver-related events and liver-related death. We also observed higher rates of the following events in nonresponders than in responders: AIDS-defining conditions (rate per 100 person years, 0.84 [95% confidence interval (CI), .59-1.10] vs 0.29 [.10-.48]; P= .003), non-liver-related deaths (0.65 [.42-.87] vs 0.16 [.02-.30]; P = .002), and non-liver-related, non-AIDS-related deaths (0.55 [.34-.75] vs 0.16 [.02-.30]; P = .002). Cox regression analysis showed that the adjusted hazard ratios of new AIDS-defining conditions, non-liver-related deaths, and non-liver-related, non-AIDS-related deaths for nonresponders compared with responders were 1.90 (95% CI, .89-4.10; P = .095), 3.19 (1.21-8.40; P = .019), and 2.85 (1.07-7.60; P = .036), respectively. Our findings suggest that eradication of HCV after therapy with interferon plus ribavirin in HIV/HCV-coinfected patients is associated not only with a reduction in liver-related events but also with a reduction in HIV progression and mortality not related to liver disease.
    Clinical Infectious Diseases 05/2012; 55(5):728-36. DOI:10.1093/cid/cis500 · 9.42 Impact Factor
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    ABSTRACT: To evaluate the incidence and risk factors for grade 3 or 4 ALT or AST elevations (TE) and grade 4 total bilirubin elevations (TBE) among HIV/HCV- coinfected treatment-naïve patients with an initial regimen including 2 nucleoside analogs plus efavirenz (EFV), nevirapine (NVP), or a ritonavir-boosted protease inhibitor (PI/r). This was a retrospective multicenter observational cohort study that recruited 745 HIV-infected drug-naïve patients with detectable plasma HCV RNA who started a regimen including EFV, NVP, or PI/r. EFV was prescribed in 323 (43%), NVP in 126 (17%), and a PI/r in 296 (40%) patients. Grade 3 or 4 TE were observed in 19 (5.9%) individuals receiving EFV compared with 14 (11%) on NVP (P = .056) and 31 (10.5%) on PI/r (P = .036). Grade 4 TBE were identified in 7 (2.2%) patients on EFV, 1 (0.8%) on NVP, and 11 (3.7%) on PI/r (P = .19). Therapy was discontinued due to liver toxicity in 13 (4%) patients on EFV, 16 (13%) on NVP, and 17 (6%) on PI/r (P = .003). Regimens including EFV, NVP, or PI/r are generally safe in treatment-naïve HIV/HCV-coinfected patients. Grade 3-4 TE are less commonly seen with EFV than with PI/r. Discontinuations due to hepatotoxicity were less frequent for patients receiving EFV than for those treated with NVP.
    HIV Clinical Trials 03/2012; 13(2):61-9. DOI:10.1310/hct1302-61 · 2.14 Impact Factor
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    ABSTRACT: The assessment of liver fibrosis is crucial for taking therapeutic decisions in patients infected with HIV/AIDS coinfected with HCV, because it allows the prognosis of the disease and the prioritization of hepatitis C treatment in these patients. A discrete events model simulation (DEMS) and a Markov model have been developed to represent the evolution of liver fibrosis to cirrhosis in patients coinfected with HIV/HVC. The model evaluated two alternatives for the diagnosis and monitoring of these patients, transient elastography performed annually and liver biopsy performed every seven years. The models have been developed under Health Care System perspective and only considered direct medical costs (disease treatment and health state costs). One-way sensitivity analyses were carried out to assess the impact of parameters with higher uncertainty. A discount rate of 3% was applied. Base case analysis shows that the diagnosis and monitoring of patients with transient elastography is a dominant strategy compared with to liver biopsy, resulting in greater life expectancy at lower cost. The sensitivity analysis performed confirmed the robustness of these results. Transient elastography has proved to be a dominant strategy compared to liver biopsy in the diagnosis and monitoring of liver fibrosis in patients coinfected with HIV/HCV in Spain.
    Enfermedades Infecciosas y Microbiología Clínica 12/2011; 30(6):294-9. · 1.88 Impact Factor
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    ABSTRACT: To assess the frequency of severe liver toxicity in HIV/hepatitis C (HCV)-coinfected patients with advanced liver fibrosis receiving efavirenz (EFV)-based antiretroviral combinations. One hundred and eighty-nine previously antiretroviral naïve, HIV/HCV-coinfected patients, who started a regimen including two nucleoside analogues plus EFV, and in whom the presence or absence of advanced liver fibrosis could be established, were retrospectively analyzed. Liver fibrosis was evaluated according to a stepwise algorithm including liver biopsy, transient elastography and FIB-4 index. Fifty-six patients had advanced fibrosis - 25 with cirrhosis - and 133 did not. Three (5.4%) subjects with and 9 (6.8%) (p=0.717) without advanced fibrosis developed grade 3-4 transaminase elevation (TE). Grade 4 total bilirubin elevation was seen in 5 (8.9%) patients with advanced fibrosis and in 1 (0.8%) without it (p=0.003). Liver events led to EFV discontinuation in 10 (5.3%) patients, 6 (10.7%) with and 4 (3%) without advanced fibrosis (p=0.031). The hepatic tolerability of EFV was good in HIV/HCV-coinfected patients with advanced liver fibrosis. The frequency of grade 3-4 TE was similar to that observed in patients without advanced fibrosis, there was no death attributable to liver failure caused by drug toxicity and the rate of EFV discontinuations due to liver events was low.
    The Journal of infection 11/2011; 64(2):204-11. DOI:10.1016/j.jinf.2011.10.016 · 4.02 Impact Factor
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    ABSTRACT: Maraviroc belongs to the family of chemokine (C-C motif) receptor 5 (CCR5) antagonists that prevent the entry of human immunodeficiency virus (HIV) into host CD4+ T cells by blocking the CCR5 co-receptor R5. Maraviroc is currently the only CC5R co-receptor inhibitor that has been approved for clinical use in HIV-1-infected patients carrying the CCR5 tropism who are antiretroviral-naïve or have experienced therapeutic failure following traditional antiretroviral therapies. This article is a review of the main characteristics of maraviroc and the latest data regarding its clinical application. Maraviroc is effective and well tolerated in pre-treated and antiretroviral-naïve patients with HIV-1 infections carrying the CCR5 tropism. Data from the phase III programme of maraviroc, which includes the MOTIVATE 1 and 2 studies and the MERIT study, indicate that maraviroc significantly (p < 0.001) increases CD4+ cell counts compared with placebo in pre-treated patients and to a similar extent as efavirenz in antiretroviral-naïve patients. Even in cases where viral load is not completely suppressed, maraviroc improves immunological response compared with placebo. In addition, promising research suggests that maraviroc has favourable pharmacokinetic and safety profiles in patients with high cardiovascular risk or those co-infected with tuberculosis or hepatitis and could be considered an option for treatment of HIV-infected patients with these co-morbidities. Resistance to maraviroc is low and mainly related to the presence of chemokine (C-X-C motif) receptor 4 (CXCR4) tropism HIV-1-infections or to mutations in the V3 region of glycoprotein (gp) 120; however, the exact mechanisms by which resistance is acquired and their genotypic and phenotypic pattern have not yet been established. It is recommended that a tropism test should be performed when considering maraviroc as an alternate drug in HIV-1-infected patients. Current tropism assays have increased sensitivity to reliably detect CXCR4 HIV with rapid turn-around and at a low cost. Improved detection together with positive data on the drug's efficacy and safety profiles should help physicians to identify more accurately the appropriate candidates for commencement of treatment with maraviroc. In summary, maraviroc improves immunological response and has shown favourable pharmacokinetic and safety profiles in patients with high cardiovascular risk or in those co-infected with tuberculosis or hepatitis. Long-term studies are needed to confirm whether therapeutic expectations resulting from clinical trials with maraviroc translate into a real benefit for HIV-1-infected patients for whom traditional antiretroviral therapies have failed or are not suitable.
    Clinical Drug Investigation 05/2011; 31(8):527-42. DOI:10.2165/11590700-000000000-00000 · 1.70 Impact Factor
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    ABSTRACT: The launch of generic forms of some of the drugs included in fixed-dose combinations of antiretrovirals (FDCA) raises the potential risk of breaking these combinations in order to allow the administration of the new cheaper generic drug. This could result in a step back in some major advances achieved in simplicity and treatment adherence, resulting in an increased risk of selective treatment withdrawal of some of the drugs administered separately. Due to the mechanism of action of the currently available antiretroviral treatment administration must be life-long in infected individuals, both children and adults.FDCA are a significant advance in antiretroviral treatment simplification, contributing to increase compliance of complex chronic therapies, thus increasing the patient's quality of life. They reduce the risk of treatment errors and can also reduce the possibility of unprescribed monotherapy with selective non-compliance. Hence, they contribute to reduce the risk of selection of HIV-1 clones with antiretroviral resistance, a situation that not only compromises future treatment options of the infected individual, but can also be transmitted and are a situation of Public Health concern. Excluding those cases that require a particular dose adjustment, FDCA are a preferred treatment option and their use must be strongly recommended in all scenarios where the components included in the combination are preferred drugs.
    Enfermedades Infecciosas y Microbiología Clínica 11/2010; 28(9):615-620. DOI:10.1016/j.eimc.2010.08.004 · 1.88 Impact Factor
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    ABSTRACT: The launch of generic forms of some of the drugs included in fixed-dose combinations of antiretrovirals (FDCA) raises the potential risk of breaking these combinations in order to allow the administration of the new cheaper generic drug. This could result in a step back in some major advances achieved in simplicity and treatment adherence, resulting in an increased risk of selective treatment withdrawal of some of the drugs administered separately. Due to the mechanism of action of the currently available antiretroviral treatment administration must be life-long in infected individuals, both children and adults. FDCA are a significant advance in antiretroviral treatment simplification, contributing to increase compliance of complex chronic therapies, thus increasing the patient's quality of life. They reduce the risk of treatment errors and can also reduce the possibility of unprescribed monotherapy with selective non-compliance. Hence, they contribute to reduce the risk of selection of HIV-1 clones with antiretroviral resistance, a situation that not only compromises future treatment options of the infected individual, but can also be transmitted and are a situation of Public Health concern. Excluding those cases that require a particular dose adjustment, FDCA are a preferred treatment option and their use must be strongly recommended in all scenarios where the components included in the combination are preferred drugs.
    Enfermedades Infecciosas y Microbiología Clínica 09/2010; 28(9):615-20. · 1.88 Impact Factor
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    ABSTRACT: Simple noninvasive tests to predict fibrosis, as an alternative to liver biopsy (LB), are needed. Of these, the aspartate aminotransferase (AST) to platelet ratio index (APRI) and the Forns index (FI) have been validated in HIV/hepatitis C virus (HCV) coinfection. However, these indexes may have lower diagnostic value in situations other than the circumscribed conditions of validation studies. We therefore examined the value of the APRI and FI in HIV/HCV-coinfected patients for the detection of significant fibrosis in real-life conditions. HIV/HCV-coinfected patients who had participated in a multicentre cross-sectional retrospective study were selected if they had undergone an LB within 24 months before the last visit. The predictive accuracy of the APRI and FI was measured using the areas under receiver-operating-characteristic curves (AUROCs). Diagnostic accuracy was determined using the positive (PPV) and negative (NPV) predictive values. A total of 519 coinfected individuals were included in the study. The AUROC [95% confidence interval (95% CI)] of the APRI was 0.67 (0.66-0.71) and that of the FI was 0.67 (0.62-0.71). The PPV of the APRI was 79% and its NPV was 66%. The PPV of the FI was 74% and its NPV was 64%. LB length was available and was > or =15 mm in 120 individuals. In this group, the PPV of the APRI was 85%, and that of the FI was 81%. Using these indexes, 22% of patients could be spared LB. Applying both models sequentially, 30% of patients could be spared LB. In HIV/HCV-coinfected patients, the diagnostic accuracy of the APRI in real-life conditions was similar to that in the validation studies. The FI performed less well. However, combining the two indexes to make decisions on anti-HCV therapy may prevent a significant proportion of patients from having to undergo LB.
    HIV Medicine 02/2010; 11(7):439-47. DOI:10.1111/j.1468-1293.2009.00812.x · 3.45 Impact Factor
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    ABSTRACT: Transient elastometry (TE) could provide a more accurate evaluation of the frequency and risk factors of liver fibrosis in hepatitis C virus (HCV) infection than that based on biopsy. The aim of this study was to assess the prevalence of and factors associated with significant liver fibrosis in a large population of HIV/HCV-coinfected patients. HIV/HCV-coinfected patients, who had participated in a cross-sectional, multicenter, retrospective study of liver fibrosis using noninvasive markers and in whom a determination of liver stiffness (LS) by TE was available, were included in this analysis. Factors potentially associated with significant fibrosis (LS ≥ 9 kPa) were analyzed. One thousand three hundred and ten patients fulfilled the inclusion criteria, 526 (40%) of them showed LS ≥ 9 kPa and 316 (24%) cirrhosis (LS ≥ 14 kPa). The factors independently associated with significant fibrosis [adjusted odds ratio (95% confidence interval, P value) were the following: older age [1.04 (1.01-1.07), 0.002], daily alcohol intake > 50 g/day [1.58 (1.10-2.27), 0.013] and the length of HCV infection [1.03 (1.00-1.06), 0.023]]. A CD4 cell count lower than < 200 per mm(3) [1.67 (0.99-2.81), 0.053] and HCV genotype 4 [0.66 (0.42-1.02), 0.066] were marginally associated with LS ≥ 9 kPa. In conclusion, the prevalence of cirrhosis in HIV/HCV-coinfected patients seems to be higher than previously reported in studies based on liver biopsy. Older age, alcohol consumption and lower CD4 cell counts are related with significant fibrosis. The latter association supports an earlier starting of antiretroviral therapy in this setting.
    Journal of Viral Hepatitis 11/2009; 17(10):714-9. DOI:10.1111/j.1365-2893.2009.01229.x · 3.31 Impact Factor
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    ABSTRACT: BACKGROUND: Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known. METHODS: We conducted two trials: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either 50 to 299 per cubic millimeter (SILCAAT) or 300 or more per cubic millimeter (ESPRIT) were randomly assigned to receive interleukin-2 plus antiretroviral therapy or antiretroviral therapy alone. The interleukin-2 regimen consisted of cycles of 5 consecutive days each, administered at 8-week intervals. The SILCAAT study involved six cycles and a dose of 4.5 million IU of interleukin-2 twice daily; ESPRIT involved three cycles and a dose of 7.5 million IU twice daily. Additional cycles were recommended to maintain the CD4+ cell count above predefined target levels. The primary end point of both studies was opportunistic disease or death from any cause. RESULTS: In the SILCAAT study, 1695 patients (849 receiving interleukin-2 plus antiretroviral therapy and 846 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 202 cells per cubic millimeter were enrolled; in ESPRIT, 4111 patients (2071 receiving interleukin-2 plus antiretroviral therapy and 2040 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 457 cells per cubic millimeter were enrolled. Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone--by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. Hazard ratios for opportunistic disease or death from any cause with interleukin-2 plus antiretroviral therapy (vs. antiretroviral therapy alone) were 0.91 (95% confidence interval [CI], 0.70 to 1.18; P=0.47) in the SILCAAT study and 0.94 (95% CI, 0.75 to 1.16; P=0.55) in ESPRIT. The hazard ratios for death from any cause and for grade 4 clinical events were 1.06 (P=0.73) and 1.10 (P=0.35), respectively, in the SILCAAT study and 0.90 (P=0.42) and 1.23 (P=0.003), respectively, in ESPRIT. CONCLUSIONS: Despite a substantial and sustained increase in the CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit in either study. (ClinicalTrials.gov numbers, NCT00004978 [ESPRIT] and NCT00013611 [SILCAAT study].)
    New England Journal of Medicine 10/2009; 361:1548-59. · 54.42 Impact Factor

Publication Stats

418 Citations
239.64 Total Impact Points

Institutions

  • 1997–2014
    • Consorcio Hospital General Universitario de Valencia
      • Departamento de Enfermedades Infecciosas
      Valenza, Valencia, Spain
  • 2012
    • Hospital Universitario Nuestra Señora de Valme
      Hispalis, Andalusia, Spain
  • 2009
    • Hospital Clínico Universitario de Valencia
      Valenza, Valencia, Spain
  • 2004
    • Hospital Universitario de Móstoles
      Madrid, Madrid, Spain
  • 2003
    • University of Oviedo
      Oviedo, Asturias, Spain