Juan Luis Gómez-Sirvent

Hospital Universitario de Canarias, San Cristóbal de La Laguna, Canary Islands, Spain

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Publications (29)99.66 Total impact

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    ABSTRACT: We characterized transmitted drug resistance to rilpivirine and the predicted efficacy of first-line rilpivirine-containing regimens in antiretroviral-naive Spanish patients. International Antiviral Society-USA mutations were detected in 138 of 2781 patients (4.9%), E138A (3.4%) being the most prevalent. Using the Stanford Algorithm, 121 patients (4.4%) showed low-level or intermediate resistance. No differences in the predicted efficacy of first-line non-nucleoside reverse transcriptase inhibitor-based regimens were observed. As rilpivirine becomes more widely used in clinical practice, the evolution of its transmitted drug resistance will need to be monitored. In addition, the exact role of E138A singletons on rilpivirine activity as part of first-line regimens merits further evaluation. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
    Clinical Microbiology and Infection 01/2015; 21(1):104.e1-5. DOI:10.1016/j.cmi.2014.08.005 · 5.20 Impact Factor
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    ABSTRACT: Our aim is to describe the impact of emtricitabine (FTC)/tenofovir (TDF) versus other nucleoside reverse transcriptase inhibitor (NRTIs)-based regimens on renal function of human immunodeficiency virus (HIV) naïve patients >50 years old who started combination antiretroviral therapy (cART). National, retrospective cohort analysis of patients >50 years old when they started cART (January 1, 2006-December 31, 2009). We compared renal safety (changes in estimated glomerular filtration rate [eGFR] during the first year, and time to renal events during 4 years of follow-up) in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitors vs non-nucleoside reverse transcriptase inhibitors and Lopinavir/ritonavir vs Efavirenz. We included 103 patients: median age: 54.9 years, 84% males, median CD4 count 247 cells/μl, median viral load 4.7 log; median follow up 18 months (max: 48 months); 73 started with FTC/TDF and 30 with other NRTIs. Change in eGFR was significantly worse for ritonavir-boosted lopinavir (LPV/r) vs efavirenz (EFV) users in the FTC/TDF group (71.2 vs 98.9 ml/min/1.73 m(2) at month 12, P < 0.05). The risk of renal events (progression to an Chronic Kidney Disease Epidemiology Collaboration value < 60 ml/min/1.73 m(2) in subjects with baseline values >60) was comparable for FTC/TDF users and non users, but was higher and almost significant for LPV/r as compared to EFV users in the FTC/TDF group (adjusted hazard ratio 6.1, 95% CI 0.8-45.5). In our study with a population of HIV infected subjects ≥ 50 years old, renal safety was similar for FTC/TDF and other NRTI-based regimens, but worse for LPV/r as compared to other regimens.
    HIV Clinical Trials 01/2015; 16(1):43-8. DOI:10.1179/1528433614Z.0000000001 · 2.14 Impact Factor
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    ABSTRACT: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.
    Journal of Antimicrobial Chemotherapy 05/2014; 69(9). DOI:10.1093/jac/dku157 · 5.44 Impact Factor
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    ABSTRACT: Objectives: Current antiretroviral guidelines state that being older than 50 to 55 years of age is an indication to start antiretroviral therapy (ART), regardless of CD4 status. However, no references to the preferred combination ART (cART) for these patients have been described. Our study compares emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) versus other nucleoside reverse transcriptase inhibitor (NNRTI) regimens in HIV ART-naïve patients who are ≥50 years. Design: National, retrospective cohort analysis of patients who were ≥50 years old when they began the first cART (January 1, 2006 to December 31, 2009). Methods: We compared safety, effectiveness, and persistence of treatment in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitor (PI) versus NNRTI users and lopinavir/r versus efavirenz users. Results: We included 161 patients: median age was 54.6 years, 83% were men, median CD4 count was 191 cells/µL, median viral load was 4.7 log, and median follow-up was 19 months (maximum, 48 months). Of these participants, 112 started with FTC/TDF and 49 with other nucleotide reverse transcriptase inhibitors (NRTIs). During follow-up, 21.9% of subjects developed at least one laboratory event ≥grade 3, 5.6% interrupted cART due to adverse events,19.3% had virologic failure, and 49.1% modified cART. There were no statistically significant differences between FTC/TDF and non-FTC/TDF users for any output except for persistence: The proportion of subjects who changed cART was 71.4% for non-FTC/TDF users and 38.6% for FTC/TDF users (log rank 0.001; adjusted hazard ratio, 2.10; 95% CI, 1.34-3.29). Conclusions: In a population of HIV-infected subjects who were ≥50 years old, our study suggests that the use of FTC/TDF is generally safe and effective, with a longer persistence as compared to other regimens.
    HIV Clinical Trials 01/2013; 14(5):204-15. DOI:10.1310/hct1405-204 · 2.14 Impact Factor
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    ABSTRACT: The major antiretroviral guidelines recommend starting ART in patients>50 y of age, regardless of CD4 cell count. However, no references to the preferred cART for these patients have been described. The combination FTC/TDF is one of the cornerstones of combined antiretroviral therapy (cART) in naïve patients. We studied the persistence of coformulated FTC/TDF in this scenario. National, retrospective cohort analysis of HIV-infected patients>50 y at the time they began the first cART regimen (January 1, 2006 - December 31, 2009). Patients were selected in a proportion 2:1 to FTC/TDF vs. other NRTI regimens (no-TDF). We compared the persistence of treatment in FTC/TDF users vs. no-TDF (main groups). Among TDF users, we compared the persistence in PI vs. NNRTI users and in lopinavir/r vs. efavirenz users. Persistence was defined as the duration of the initial treatment; we analyzed time to any change or discontinuation according to initial regimen. We included 161 patients: median age: 54.6 y, 83% males, median CD4 count 191 cells/μl, median viral load 4.7 log, follow up: median 19 months, max 48 months. Of them, 112 started with FTC/TDF (53 with PIs, 57 with NNRTIs); and 49 with other NRTIs (no-TDF) (22 with PI, 23 NNRTI). During the follow-up period 79 patients (49%) modified their treatment, with statistically significant differences among groups, as shown in Table 1.*Adjusted by age, sex, transmission category and baseline CD4 count and viral load.In our study (antiretroviral-naïve patients>50 y), the persistence of FTC/TDF regimens was significantly higher than other NRTI regimens. According to the third agent, there was a trend to a higher persistence with NNRTI vs. PI. This reaches statistical significance when we compare EFV vs. LPV/r. In the absence of randomized clinical trials, our data may contribute to a better understanding on how cART works in this ageing population, which is progressively increasing.
    Journal of the International AIDS Society 11/2012; 15(6):18292. DOI:10.7448/IAS.15.6.18292 · 4.21 Impact Factor
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    ABSTRACT: Purpose: In the last decade the prevalence of HIV-infected patients≥50 years of age has increased. FTC/TDF is nowadays one of the cornerstones of cART in naïve patients, generally considered safe and well tolerated; nevertheless there is a continuous debate about the renal safety of TDF, due to the report of cases linking this treatment with renal failure and tubular dysfunction. In addition, there is a well-recognized age-related decline in renal function. Our aim was to describe the impact of cART regimen (FTC/TDF vs. others) on renal function of subjects who start cART at≥50 years old. Methods: National, retrospective cohort analysis of HIV-infected patients>50 y at the time they began the first cART (Jan 1, 2006 - Dec 31, 2009). Patients were selected in a proportion 2:1 to FTC/TDF versus other NRTI regimens (no TDF). For this analysis we excluded subjects taking potentially nephrotoxic drugs at baseline. We compared the impact of FTC/TDF vs. no-TDF regimens (main groups) on renal function by means of the changes, during the first 12 months of treatment, in glomerular filtration rate estimated by the CKD-EPI formula, and by the analysis of time to renal deterioration during the complete follow up (defined as progression to an EPI-CKD value<60 mL/min/1.73 m2 in subjects with baseline values>60). We also compared these outcomes among FTC/TDF users, according to the third agent: PI vs. NNRTI, and lopinavir/r vs. efavirenz. Results: We included 125 patients, median age: 54.8 y, 82% males, median CD4 count 235 cells/µl, median viral load 4.7 log, follow up: median 19 months, max: 66 months. Of them, 82 started with FTC/TDF and 43 with other NRTIs (no TDF). During the follow-up 13/125 patients taking FTC/TDF (11%) presented with renal deterioration. The Cox regression model including age, sex, transmission category, baseline CD4 count and viral load, FTC/TDF use, PI/NNRTI use, and LPVr/EFV use showed a hazard ratio for renal deterioration of 4.13 (95% CI 0.92, 18.5) for LPV/r users. The table shows the evolution of glomerular filtration rate, and proportion and risk of renal deterioration. Conclusion: In subjects starting cART after 50 years of age, we have not found significant changes in glomerular filtration rate associated with the use of FTC/TDF-based regimens. Overall, the risk of renal deterioration was 4.1 times higher for LPV/r users (almost statistically significant). Among FTC/TDF users, this risk was 8 times higher for LPV/r as compared to EFV.
    Journal of the International AIDS Society 11/2012; 15(6):18312. DOI:10.7448/IAS.15.6.18312 · 4.21 Impact Factor
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    ABSTRACT: Purpose of the study: Very scarce information has been published to date with the combination of ABC/3TC/NVP but it is currently being used in clinical practice in many centers in Spain. Our aim was to present the clinical experience with this regimen in a cohort of adult HIV-infected pts. Methods: Retrospective, multicenter, cohort study. Consecutive adult HIV-infected ARV-experienced pts, HLA-B*5701-negative, who started ABC/3TC/NVP between 2005-2010, with at least one follow-up visit, were included. Demographic, clinical and laboratory variables were assessed at baseline, month 1, and every 3-4 months thereafter. The primary end point was HIV-1 viral load (VL) <40 c/mL at 48 weeks. Data were analyzed by intent-to-treat (ITT) (non-completer=failure) and on treatment (OT). Summary of results: 227 pts were included and followed up for a median of 30 (0.5-76) months. 75% male, 47 (24-83) years, 21% AIDS, 13% HCV+, baseline CD4 570 (32-1404) cells/µL and VL undetectable in 90% with a median of <1.59 (<1.59-5.1) log. Most pts were receiving NVP (63%), ABC (25%) or both (4%) in the previous regimen. ABC/3TC/NVP was initiated due to toxicity (42%), simplification (35%) or other reasons (22%) including to reduce drug cost. After 48 weeks, VL was <40 c/mL in 82% (ITT) and 94% (OT), and in 94% (OT) after 96 weeks. CD4 increased +63 (p<0.001) and +77 (p<0.001) cells/µL after 48 and 96 weeks, respectively. One or more drugs of the regimen were discontinued in 18% of pts during follow up: toxicity (7%), virologic failure (3%), lost to follow-up (3%), unrelated death (0.4%) or other reasons (4%). No significant differences were observed in ALT, AST, or triglyceride changes during follow up. A significant increase of 7%, 10% and 14% was observed in total cholesterol, LDLc and HDLc, and a significant decrease in TC/HDL ratio (-5%, p=0.004) after 96 weeks, respectively. Conclusions: In this particular cohort of ARV-experienced pts previously receiving NVP or ABC, a combination of ABC/3TC/NVP was safe and mantained virologic suppression in the vast majority of pts, with rates similar to other switch strategies. A favourable lipid profile was observed after 96 weeks of follow up.
    Journal of the International AIDS Society 11/2012; 15(6):18343. DOI:10.7448/IAS.15.6.18269 · 4.21 Impact Factor
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    ABSTRACT: BACKGROUND AND AIMS: Most studies have shown that patients with chronic hepatitis C virus (HCV) infection are affected by osteoporosis. However, liver function impairment and deranged nutrition may both play a role in the bone alterations observed. In some works no osteoporosis was found, and some cases of osteosclerosis have been reported. The aim of the study is to assess bone alterations in treatment-naïve, well-nourished HCV patients, in order to discern whether or not HCV infection causes osteoporosis. METHODS: Whole-body bone densitometry and assessment of T-score at lumbar spine and hip were performed to 40 patients and 40 age- and sex-matched controls, with a Lunar Prodigy Advance (General Electric, Piscataway, NJ, USA). All the patients underwent liver biopsy. Nutritional evaluation was performed by subjective nutritional assessment, body mass index (BMI), and densitometric assessment of total lean mass and total fat mass. Serum osteocalcin, osteoprotegerin, RANKL, PTH, crosslaps, vitamin D3, testosterone, IGF-1, and estradiol were determined. RESULTS: Patients did not show differences in total bone mineral density (BMD) or T-score with controls. On the contrary, about a third of them showed positive T scores. Patients showed lower IGF-1, vitamin D3 and testosterone, but higher telopeptide levels, and a trend to higher osteoprotegerin levels. Multivariate analyses disclosed that age, sex, and total lean mass were the only parameters independently related with BMD. CONCLUSIONS: Therefore, chronic HCV infection in well nourished patients with preserved liver function does not cause osteoporosis.
    European Journal of Internal Medicine 09/2012; DOI:10.1016/j.ejim.2012.09.007 · 2.30 Impact Factor
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    ABSTRACT: OBJECTIVE:: To study trends in overall deaths and cause-specific deaths stratified by HCV serostatus in a cohort of combined antiretroviral (cART)-naïve HIV-infected patients in Spain METHODS:: We analyzed data from 1997 to 2008 in 2 calendar periods: 1997-2003 and 2004-2008. Deaths were ascertained through cohort reporting and a cross-match with the Spanish National Death Index. We used Poisson regression to model mortality rates and risk factors. RESULTS:: We analyzed 5,974 HIV-positive cART-naïve patients: 2,471 (1,497 HCV+) in the period 1997-03, and 3,503 (689 HCV+) in the period 2004-08. A total of 232 deaths (158 during the first period, and 74 during the second period) were detected during 19,416 person-years (PYs) of follow-up; the death rate was 12.9/1,000 PYs. Crude overall death rates (95% CI) were 16.5 (14.2-19.1) in 1997-2003 and 8.5 (6.7-10.6) in 2004-08. The incidence rate ratio (IRR) (95%CI) in 2004-08 taking 1997-03 as a reference was 0.51 (0.39-0.67). When we stratified by HCV serostatus, the overall death IRR (95% CI) taking 1997-03 as reference was 0.52 (0.32-0.85) for HCV-negative patients and 1.27 (0.90-1.79) for HCV-positive patients. When we considered cause-specific deaths (liver-related, AIDS-related, and non-liver-related/non-AIDS-related), findings were similar to those for overall-deaths. CONCLUSIONS:: Taking the first years of the cART era as a reference, we observed a decrease in overall and cause-specific mortality. This decrease was only observed in HCV-negative patients.
    AIDS (London, England) 07/2012; 26(17). DOI:10.1097/QAD.0b013e3283574e94 · 6.56 Impact Factor
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    ABSTRACT: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/μL, 19% CD4 < 200/μL, 27% ALT grade 1-2, 36% AST grade 1-2. Thirty percent ART-naive, 83%received NVP associated with 2 nucleoside analogues during the study period, and 17% a protease inhibitor. A significant improvement was observed in general health status markers, including hemoglobin, platelets, and albumin, regardless of HCV coinfection. CD4 cell gain was +218 and +322/μL after 6 and 9 years, respectively (+321 and +391 in naive patients). Triglycerides significantly decreased in pretreated patients, whereas the percentage of patients with HDLc < 1.03 mmol/L and LDL-c > 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.
    Current HIV research 06/2012; 10(6):513-20. DOI:10.2174/157016212802429820 · 2.14 Impact Factor
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    ABSTRACT: BACKGROUND: The aim of this study was to investigate the incidence and risk factors for the development of AIDS-defining cancers (ADCs); and to investigate the effect of making different assumptions on the definition of incident cases. METHODS: A multicentre cohort study was designed. Poisson regression was used to assess incidence and risk factors. To account for misclassification, incident cases were defined using lag-times of 0, 14 and 30 days after enrolment. RESULTS: A total of 6393 HIV-positive subjects were included in the study. The incidences of ADCs changed as the lag periods were varied from 0 to 30 days. Different risk factors emerged as the definition of incident cases was changed. For a lag time of 0, the risk of Kaposi sarcoma [KS] and non-Hodgkin lymphoma [NHL] increased at CD4 counts <200/ml. HAART was associated with lower risk of NHL and KS. Men who had sex with men had a higher risk of KS. KS and NHL were not associated with viral load, gender, or hepatitis B or C. The results were similar for a lag-time of 14 and 30 days; however, hepatitis C was significantly associated with NHL. CONCLUSIONS: This analysis shows the importance of the definition of incident cases in cohort studies. Alternative definitions gave different incidence estimates, and may have implications for the analysis of risk factors.
    Enfermedades Infecciosas y Microbiología Clínica 05/2012; 31(5). DOI:10.1016/j.eimc.2012.03.009 · 1.88 Impact Factor
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    ABSTRACT: The presence of resistance mutations in patients failing tipranavir or darunavir was examined at the national drug resistance database of the Spanish AIDS Research Network. Although mutations emerging during tipranavir and darunavir failures differed considerably, cross-resistance was found in up to half of the patients tested. Interestingly, mutation 54L, which is associated with tipranavir hypersusceptibility, was selected in half of the darunavir failures. Thus, resistance testing seems mandatory to ensure the benefit of the sequential use of these drugs.
    Antimicrobial Agents and Chemotherapy 07/2010; 54(7):3018-20. DOI:10.1128/AAC.00160-10 · 4.45 Impact Factor
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    ABSTRACT: A proportion of HIV-patients does not normally restore their CD4 counts despite virological response to HAART. Those whose CD4 counts persistently remain closed to the critical threshold for opportunistic infections deserve special interest. To study the risk factors, the long-term CD4 counts evolution, and the risk of death of patients who persistently maintain low CD4 counts, despite virological response to HAART, within a multicenter, hospital-based cohort study. A total of 147 patients were selected from CoRIS-MD and classified into a "Low-Group" or a "High-Group", depending on their CD4 counts after two-years of effective HAART (threshold 250 cells/microL). Associated risk factors were analysed by logistic regression, the CD4 dynamics were evaluated over a total period of 7.70 years (IQR, 6.70-9.00), and mortality was estimated by Cox proportional hazard. A total of 40 patients (27%) were classified into the "Low-Group". The odds ratio for this group increased with age, being 4.56 (2.23-9.33) for over 40, and was also higher among IDU, 3.63 (1.04-12.68). Six years thereafter, among these patients, only a 30% exceeded 350 CD4 cells/microL and a 12% exceeded 500 CD4 cells/microL. Furthermore, the "Low-Group" had a death rate of 2.42 per 100 persons/year (95%CI, 1.01-5.81), although once adjusted by age the estimates were no longer significant [4.14 (0.87-19.72)]. Our results suggest that those HIV patients who have not overcome the critical threshold of 250 CD4 cells/microL after a two years period of virologically effective HAART do persist with the aforementioned failure of CD4 restoration for a much longer time.
    Current HIV research 11/2009; 7(6):612-9. DOI:10.2174/157016209789973673 · 2.14 Impact Factor
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    ABSTRACT: To estimate incidence rates and risk factors for tuberculosis (TB) in human immunodeficiency virus seroprevalent subjects. Multicentre, hospital-based cohort study of patients presenting to 10 Spanish hospitals from 1 January 1997 to 31 December 2003. Poisson regression was used and highly active antiretroviral treatment (HAART) was modelled as a time-dependent covariate. A total of 4268 patients were followed for a median of 3.8 years; 221 TB cases were diagnosed over 16 464 person-years (py). TB rates were higher in HAART-naïve subjects (1.56 per 100 py, 95%CI 1.36-1.79) than those on HAART (0.5/100 py, 95%CI 0.31-0.80). Among HAART-naïves, TB risk factors were: being male, being an injecting drug user (IDU) (RR 2.01, 95%CI 1.28-3.16), having low CD4 counts (P < 0.001) and high viral loads (P < 0.001). HAART was protective (RR 0.26, 95%CI 0.16-0.40) and reductions in TB rates were observed in the last calendar period (RR 0.74, 95%CI 0.55-1.00). For patients on HAART, no differences were observed by category of transmission. Low CD4 counts at entry were associated with higher TB rates (P < 0.001). HAART was associated with lower TB rates, and TB risk factors differed according to whether or not patients had received HAART. To further reduce TB rates, additional strategies are needed, such as timely access and adherence to HAART, especially in IDUs.
    The International Journal of Tuberculosis and Lung Disease 12/2008; 12(12):1393-400. · 2.76 Impact Factor
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    ABSTRACT: OBJECTIVE: To estimate incidence rates and risk factors for tuberculosis (TB) in human immunodeficiency virus seroprevalent subjects. METHODS: Multicentre, hospital-based cohort study of patients presenting to 10 Spanish hospitals from 1 January 1997 to 31 December 2003. Poisson regression was used and highly active antiretroviral treatment (HAART) was modelled as a time-dependent covariate. RESULTS: A total of 4268 patients were followed for a median of 3.8 years; 221 TB cases were diagnosed over 16464 person-years (py). TB rates were higher in HAART-naïve subjects (1.56 per 100 py, 95%CI 1.36-1.79) than those on HAART (0.5/100 py, 95%CI 0.31-0.80). Among HAART-naïves, TB risk factors were: being male, being an injecting drug user (IDU) (RR 2.01, 95%CI 1.28-3.16), having low CD4 counts (P < 0.001) and high viral loads (P < 0.001). HAART was protective (RR 0.26, 95%CI 0.16-0.40) and reductions in TB rates were observed in the last calendar period (RR 0.74, 95%CI 0.55-1.00). For patients on HAART, no differences were observed by category of transmission. Low CD4 counts at entry were associated with higher TB rates (P < 0.001). CONCLUSIONS: HAART was associated with lower TB rates, and TB risk factors differed according to whether or not patients had received HAART. To further reduce TB rates, additional strategies are needed, such as timely access and adherence to HAART, especially in IDUs.
    The International Journal of Tuberculosis and Lung Disease 12/2008; 12(12):1393-1400. · 2.76 Impact Factor
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    ABSTRACT: A major cause of liver cirrhosis and hepatocarcinoma is chronic infection by hepatitis C virus. Ethanol consumption is the most significant environmental factor that exacerbates the progression of chronic hepatitis C to liver cirrhosis and hepatocarcinoma, perhaps due to increased cytokine secretion together with increased lipid peroxidation. In this study, we compare the intensity of lipid peroxidation (estimated as malondialdehyde (MDA) serum levels), the antioxidant status, (measured as glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities in red blood cells), and levels of cytokines derived from Th1 cells (such as interferon gamma (IFNG)), Th2 cells (such as interleukin (IL)-4), Th3 cells (such as transforming growth factor beta (TGF-beta)), and IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in patients affected by chronic hepatitis C virus infection, 26 drinkers of alcohol and 40 nondrinkers of alcohol. Patients showed significantly higher TNF-alpha (Z = 4.92, P < 0.001), IL-8 (Z = 4.95, P < 0.001), IFNG (Z = 2.81, P = 0.005), TGF-beta (t = 2.12, P = 0.037), MDA (Z = 5, P < 0.001), but lower IL-6 (Z = 3.61, P < 0.001) and GPX (F = 4.30, P < 0.05) than controls, whereas no differences were observed regarding IL-4 (Z = 0.35, P = 0.72), GPX and SOD activities. Alcoholics showed significantly higher TNF-alpha, but lower IL-4, MDA, and GPX, than nonalcoholics. TNF-alpha was significantly related to albumin and prothrombin activity, whereas TGF-beta was significantly related to MDA levels. Thus, cytokine secretion is altered in HCV infection. This alteration mainly consists of a stimulation of Th1 cytokines and an inhibition--or at least, no stimulation--of Th2 cytokines; these changes are especially marked among alcoholics with HCV infection, and are accompanied by raised TGF-beta.
    Alcohol and Alcoholism 01/2008; 43(2):137-42. DOI:10.1093/alcalc/agm171 · 2.09 Impact Factor
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    ABSTRACT: Enfuvirtide is a high-cost, parenterally administered drug commonly used in late phases of HIV infection, when its efficacy may be compromised. To optimize enfuvirtide use, consensus recommendations for this purpose have been formulated by 247 physicians attending patients with HIV infection in Spain. A literature review was performed in which grades of evidence and recommendations were defined according to the origin of the data (randomized clinical trials, non-randomized studies, expert opinion). Twenty-eight local consensus meetings were held between May and September 2005 to discuss the most important aspects related to the use of enfuvirtide, following a pre-established system used in all the meetings. The main conclusions were as follows: a) enfuvirtide use is often excessively delayed and is given to patients with little chance of treatment success; b) enfuvirtide is indicated in patients who require antiretroviral treatment and for whom an optimum treatment with three other fully effective drugs cannot be designed; c) the most important prognostic factor is the availability of at least one other completely active drug; d) there is no infallible method to avoid the development of local reactions, but measures are available to decrease their incidence and severity; and e) patient counseling and training for correct administration of the drug are essential to improve adherence, the repercussions of local reactions and, of course, the efficacy of the treatment.
    Enfermedades Infecciosas y Microbiología Clínica 03/2007; 25(2):131-42. · 1.88 Impact Factor
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    ABSTRACT: To describe the methodology and baseline results of the Spanish cohort of naïve HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). CoRIS is a multicenter, hospital-based prospective cohort of HIV sero-prevalent, retroviral-naïve subjects, over 13 years old, and seen at 17 hospitals in 8 of the 17 Autonomous Regions in Spain from January 2004 to October 2005. The socio-demographic characteristics, as well as epidemiological, clinical, laboratory and treatment data were recorded, and biological samples were collected at baseline and during follow-up. A total of 1,591 subjects have been included in CoRIS; 24% are women, median age at cohort entry is 36 years, and 74% were diagnosed during 2004 or 2005. Twenty-seven percent came from countries other than Spain, mainly Latin-America (16%) and sub-Saharan Africa (5%). Thirty-two percent had completed secondary education and 16% university studies. The most frequent categories of transmission were men having sex with men (37%) and heterosexual sex (36%); only 21% were injection drug users. At cohort entry, median CD4 count was 317 cells/mm 3 and median viral load was 52,300 copies/mL; 18% were diagnosed with AIDS. Main AIDS-defining illnesses were Pneumocystis jiroveci pneumonia (6.1%), esophageal candidiasis (3.3%) and tuberculosis (extrapulmonary, 3.0% and pulmonary 2.7%). There were 35 deaths (2.2%). Thirty-three percent of patients gave a baseline sample to the BioBank. CoRIS offers relevant information about the current epidemiological profile of HIV infection in Spain, where sexual transmission has become predominant. The type and amount of information obtained from clinical and epidemiological data collection together with biological samples demonstrate the viability of the project, which offers many possibilities for future research.
    Enfermedades Infecciosas y Microbiología Clínica 02/2007; 25(1):23-31. · 1.88 Impact Factor
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    ABSTRACT: Enfuvirtide is a high-cost, parenterally administered drug commonly used in late phases of HIV infection, when its efficacy may be compromised. To optimize enfuvirtide use, consensus recommendations for this purpose have been formulated by 247 physicians attending patients with HIV infection in Spain. A literature review was performed in which grades of evidence and recommendations were defined according to the origin of the data (randomized clinical trials, non-randomized studies, expert opinion). Twenty-eight local consensus meetings were held between May and September 2005 to discuss the most important aspects related to the use of enfuvirtide, following a pre-established system used in all the meetings. The main conclusions were as follows: a) enfuvirtide use is often excessively delayed and is given to patients with little chance of treatment success; b) enfuvirtide is indicated in patients who require antiretroviral treatment and for whom an optimum treatment with three other fully effective drugs cannot be designed; c) the most important prognostic factor is the availability of at least one other completely active drug; d) there is no infallible method to avoid the development of local reactions, but measures are available to decrease their incidence and severity; and e) patient counseling and training for correct administration of the drug are essential to improve adherence, the repercussions of local reactions and, of course, the efficacy of the treatment.
    Enfermedades Infecciosas y Microbiología Clínica 02/2007; 25(2):131–142. DOI:10.1157/13098573 · 1.88 Impact Factor
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    ABSTRACT: Objective To describe the methodology and baseline results of the Spanish cohort of naïve HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). Methods CoRIS is a multicenter, hospital-based prospective cohort of HIV sero-prevalent, retroviral-naïve subjects, over 13 years old, and seen at 17 hospitals in 8 of the 17 Autonomous Regions in Spain from January 2004 to October 2005. The socio-demographic characteristics, as well as epidemiological, clinical, laboratory and treatment data were recorded, and biological samples were collected at baseline and during follow-up. Results A total of 1,591 subjects have been included in CoRIS; 24% are women, median age at cohort entry is 36 years, and 74% were diagnosed during 2004 or 2005. Twenty-seven percent came from countries other than Spain, mainly Latin-America (16%) and sub-Saharan Africa (5%). Thirty-two percent had completed secondary education and 16% university studies. The most frequent categories of transmission were men having sex with men (37%) and heterosexual sex (36%); only 21% were injection drug users. At cohort entry, median CD4 count was 317 cells/mm3 and median viral load was 52,300 copies/mL; 18% were diagnosed with AIDS. Main AIDS-defining illnesses were Pneumocystis jiroveci pneumonia (6.1%), esophageal candidiasis (3.3%) and tuberculosis (extrapulmonary, 3.0% and pulmonary 2.7%). There were 35 deaths (2.2%). Thirty-three percent of patients gave a baseline sample to the BioBank. Conclusions CoRIS offers relevant information about the current epidemiological profile of HIV infection in Spain, where sexual transmission has become predominant. The type and amount of information obtained from clinical and epidemiological data collection together with biological samples demonstrate the viability of the project, which offers many possibilities for future research.
    Enfermedades Infecciosas y Microbiología Clínica 01/2007; 25(1):23–31. DOI:10.1157/13096749 · 1.88 Impact Factor

Publication Stats

263 Citations
99.66 Total Impact Points

Institutions

  • 2002–2015
    • Hospital Universitario de Canarias
      San Cristóbal de La Laguna, Canary Islands, Spain
  • 2008–2012
    • Universidad de La Laguna
      San Cristóbal de La Laguna, Canary Islands, Spain
  • 2000
    • Hospital Universitari Germans Trias i Pujol
      Badalona, Catalonia, Spain
  • 1996
    • Hospital Clínic de Barcelona
      • Servicio de Enfermedades Infecciosas
      Barcino, Catalonia, Spain