PubMed | Hospital Universitario Torrecardenas, Hospital Universitario Of Gran Canaria Dr Negrin, Hospital Universitario Of Valme, Hospital Universitario Alvaro Cunqueiro and 5 more.
Type: | Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases | Year: 2017
The aim of this study was to determine the predictive capacity of response at treatment week (TW) 4 for the achievement of sustained virologic response 12 weeks after the scheduled end of therapy date (SVRFrom a prospective multicohort study, HCV GT3-infected patients who completed a course of currently recommended DAA-based therapy at 33 Spanish hospitals and who had reached SVRA total of 123 patients were included, 86 (70%) subjects received sofosbuvir/daclatasvir+/-ribavirin, 27 (22%) sofosbuvir/ledipasvir/ribavirin and 10 (8.1%) sofosbuvir/ribavirin, respectively. One-hundred and fourteen out of 123 (92.7%) patients presented SVRTW4-response indicates the probability to achieve SVR
PubMed | Hospital Universitario La Paz, Complejo Hospitalario Of Huelva, Hospital Virgen Macarena, Hospital Universitario Of Valme and 10 more.
Type: Journal Article | Journal: Journal of the International AIDS Society | Year: 2014
Although hepatotoxicity related to antiretroviral treatment (ART) has become less frequent, hepatotoxic events, such as transaminase elevations (TE), are still a matter of concern. RPV/FTC/TDF (EPA) is a new single tablet regimen which is widely used in real life practice. Clinical trials showed an adequate profile of liver safety in the sub-population of HIV/HCV-coinfected patients receiving rilpivirine. However, the number of individuals included in these analyses is low (1). The aim of this ongoing study is to evaluate the incidence of TE and total bilirubin elevations (TBE) during the first 48 weeks of EPA-based therapy in a large population of HIV/HCV-coinfected subjects outside of clinical trials.This is a retrospective analysis of HIV/HCV-coinfected subjects who started EPA at the infectious diseases units of 14 centres throughout Spain, included as cases. Subjects who started an ART different to EPA during the study period at the same hospitals were selected as controls. The primary outcome variables were grade 3 or 4 TE and grade 4 TBE.Of the 191 patients included, 31 (16.2%) subjects were nave to ART. Eighty-seven individuals started EPA and the remaining ones were controls. The most common NRTI backbone among the controls was TDF/FTC [59 (56.7%) patients] followed by NRTI-sparing regimens [24 (23.1%) individuals] and ABC/3TC [17 (16.3%) subjects]. Among controls, 67 (64.4%) started a ritonavir-boosted protease inhibitor, mainly DRV/r [41 (39.4%) patients] followed by ATV/r [16 (15.4%) subjects]. EFV, ETV and RAL were started in 16 (15.4%), 12 (11.5%) and 13 (12.5%) subjects, respectively. The median (Q1-Q3) follow-up was 5.79 (3.65-8.61) months for the cases and 11.44 (5.8-12.88) months for the controls. TE was observed in two (2.3%) cases versus five (4.8%) controls (p=0.358), accounting for a density of incidence of 4.32/100 person-years versus 5.51/100 person-years [incidence rate difference (95% confidence interval): -1.88 (-9.95-6.2), p=0.354]. All TE were grade 3 and no patient discontinued ART due to TE. None of the cases developed TBE versus four (3.8%) controls, all of them receiving ATV/r.The frequency of grade 3-4 TE associated with EPA in HIV/HCV-coinfected patients under real life conditions is very low. In addition, TE in HIV/HCV-coinfected patients treated with EPA are usually mild and do not lead to treatment discontinuation. TBE was not seen in patients taking EPA. All these data confirm that EPA is safe in this particular subpopulation.
PubMed | Hospital Regional Universitario Virgen Of La Victoria, Hospital Universitario San Cecilio, Complejo Hospitalario Of Jaen, Hospital Regional Universitario Carlos Haya and 13 more.
Type: | Journal: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology | Year: 2016
In April 2015, the Spanish National Health System (SNHS) developed a national strategic plan for the diagnosis, treatment, and management of hepatitis C virus (HCV). Our aim was to analyze the impact of this on human immunodeficiency virus (HIV)-infected patients included in the HERACLES cohort during the first 6months of its implementation. The HERACLES cohort (NCT02511496) was set up in March 2015 to evaluate the status and follow-up of chronic HCV infection in patients co-infected with HIV in the south of Spain. In September 2015, the data were analyzed to identify clinical events (death, liver decompensation, and liver fibrosis progression) and rate of treatment implementation in this population. The study population comprised a total of 3474 HIV/HCV co-infected patients. The distribution according to liver fibrosis stage was: 1152F0-F1 (33.2%); 513F2 (14.4%); 641F3 (18.2%); 761F4 (21.9%); and 407 whose liver fibrosis was not measured (12.3%). During follow-up, 248 patients progressed by at least one fibrosis stage [7.1%; 95% confidence interval (CI): 6.3-8%]. Among cirrhotic patients, 52 (6.8%; 95% CI: 5.2-8.9%) developed hepatic decompensation. In the overall population, 50 patients died (1.4%; 95% CI: 1.1-1.9%). Eight hundred and nineteen patients (23.56%) initiated interferon (IFN)-free treatment during follow-up, of which 47.8% were cirrhotic. In our study, during 6months of follow-up, 23.56% of HIV/HCV co-infected patients included in our cohort received HCV treatment. However, we observed a high incidence of negative short-term outcomes in our population.
PubMed | Hospital Universitario San Cecilio, Complejo Hospitalario Of Jaen, Hospital Universitario Virgen Of Las Nieves, Hospital Universitario Puerta del Mar and 8 more.
Type: Clinical Trial | Journal: PloS one | Year: 2014
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.ClinicalTrials.gov NCT01437241.
PubMed | Hospital Universitario Virgen Of La Macarena, Complejo Hospitalario Of Huelva, Hospital La Linea, Hospital Universitario Of Valme and 4 more.
Type: | Journal: BMC infectious diseases | Year: 2016
Acute hepatitis C virus (HCV) infection (AHCVI) outbreaks have been described recently within defined areas worldwide among HIV-infected homosexual men. This study aims to describe the cumulative frequency and incidence of firstly acquired AHCVI in an HIV-infected population in Southern Spain.This is a retrospective study conducted at the Infectious Diseases Units of eight hospitals in Andalusia, Southern Spain. Primary AHC was considered as HCV immunoglobulin G antibody seroconversion. The time of infection was considered the moment between the last negative and the first positive HCV antibody determination.A total of 23 cases of primary AHCVI have been detected from 2000 to 2014. Incidence rates [IR; 95% confidence interval (CI)] were 0.036 (2.272-0.054) per 100 person-years (py) in the overall population over a follow-up period of 64170 py. Of the 22 (95.7%) male subjects, 21 (95.5%) had acquired AHCVI by homosexual contact, the IR (95% CI) was 0.039 (0.024-0.06) per 100 py in this subpopulation. There was no evidence of an increase of AHCVI IR. The incidence of AHCVI was slightly lower between 2000 and 2004 as compared to 2005-2009 [IR ratio (IRR) of 8.8 (95% CI: 1.279-378.794; p=0.01)] but reached a plateau afterwards [IRR between 2010 and 2014 versus 2005-2009: 0.727 (0.286-1.848; p=0.5)]. The median (Q1-Q3) time between the last negative anti-HCV and the first positive anti-HCV determination was 4.7 (1.9-11.2) months. Peak (Q1-Q3) ALT and total bilirubin values during AHCVI were 496 (291-656) IU/mL and 1.15 (0.9-1.98) mg/dL, respectively.In contrast to what has been reported from other areas, the incidence of primary AHCVI in the HIV-infected population is stable in Southern Spain and there is no evidence of an epidemic, in spite of the high prevalence of HIV/HCV-coinfection in this area.
PubMed | Hospital Regional Universitario Virgen Of La Victoria, Hospital Universitario San Cecilio, Complejo Hospitalario Of Jaen, Hospital Regional Universitario Carlos Haya and 9 more.
Type: Journal Article | Journal: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology | Year: 2015
The implementation of hepatitis C (HCV) direct-acting antiviral drugs is prioritized in several populations in which its application provides the most immediate and impactful benefit. In this scenario, a precise knowledge of the situation of human immunodeficiency virus (HIV)/HCV chronic co-infection is required to adequately address this disease. This cross-sectional study was performed in 21 hospitals in Andalusia (Spain). The study population consisted of HIV-infected patients with an active HCV chronic infection who were not receiving HCV treatment at the time of inclusion. A total of 13,506 HIV-infected patients were included in the study. Of them, 2561 (18.9%) presented chronic HCV infection. The majority of the patients included were on highly active antiretroviral therapy (HAART; 96.2%), showed plasma levels with an undetectable HIV viral load (92.5%), and had a good immunological status (median CD4+ cell count of 486 cells/mL). The HCV genotype distribution was as follows: 58.1% were genotype 1, 1.1% were genotype 2, 16.1% were genotype 3, and 22.1% were genotype 4 (2.6% were missing data). In total, 24.8% of the patients showed liver fibrosis stage F0-F1, 27.9% showed stage F2, 16.7% showed stage F3, and 21% showed stage F4 (9.6% were missing data). With regards to previous HCV treatment experiences, 68.05% of the patients were nave and 31.95% had failed to respond to a previous treatment. The burden of HCV/HIV co-infected patients in our population was reported as one in five HIV-infected patients requiring HCV treatment. The implementation of extra resources to face this important health challenge is mandatory.
PubMed | Hospital Universitario San Cecilio, Hospital Universitario Virgen Of Las Nieves, Complejo Hospitalario Juan Ramon Jimenez, Hospital Universitario Virgen Of La Victoria and 6 more.
Type: Journal Article | Journal: PloS one | Year: 2016
Significant controversy still exists about ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv) as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF) while on protease inhibitor (PI) -based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI-based regimens.This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure).A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis) and virological efficacy (on-treatment analysis) at week 96 were 79.3% (CI95, 76.8-81.8) and 91.5% (CI95, 89.6-93.4), respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV-coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations.Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for the administered drug.
PubMed | Institute Investigacion Of Biomedicina Of Malaga Ibima, Hospital Comarcal Of La Axarquia, Hospital La Linea, Hospital Comarcal Of Antequera and 3 more.
Type: Journal Article | Journal: The Journal of antimicrobial chemotherapy | Year: 2016
We describe the characteristics of an HIV-1 strain with six viral reverse transcriptase mutations (D67N, T69N/D, V118I, V179D, T215S and K219Q), which we have called the Malaga strain. This strain was detected in treatment-naive patients from southern Spain.The study was undertaken at the Virgen de la Victoria Hospital, Malaga, a reference centre for the study of HIV-1 genotype resistance in Andalusia (the Costa del Sol), Spain. Genotypic resistance testing was done in an automated sequencer. Phylogenetic analysis was performed using a 630 bp region of the reverse transcriptase with the mutations mentioned.Between 2007 and 2014, we detected the Malaga strain in 30 treatment-naive patients. All were MSM, seen at five hospitals on the Costa del Sol. In all cases, the HIV-1 was subtype B with viral tropism R5. Phylogenetic analysis based on the reverse transcriptase sequence showed consistent grouping (with a bootstrap value of the common node of 100%) of the isolates that shared the mutation pattern mentioned. This strain has not been detected elsewhere or in previously treated patients. All of the patients treated with first-line combination ART responded.We report a cluster of an HIV-1 strain with multiple resistance mutations that was transmitted over a period of >8 years, affecting 30 naive patients from the same geographical area. The strain was susceptible to first-line combination ART.
PubMed | Hospital La Linea
Type: | Journal: Ecancermedicalscience | Year: 2013
Our objective was to determine the identification and the percentage of false negatives in sentinel node biopsies in patients with early breast cancer at the Hospital La Lnea (Spain), during the period between November 2007 and September 2010.We collected 50 patients with early breast cancer, without clinical and ultrasonographic involvement of axillary nodes, from November 2007 to September 2010. We used the vital dye in the first 20 patients and the combined technique of vital dye and albumin labelled with technetium 99 in the other 30 patients. The site of injection for patients using blue dye was subdermal for palpable tumours and periareolar for non-palpable tumours. The technique of injection with the radioisotope for patients for palpable and most non-palpable tumours was the periareolar technique. We used albumin labelled with technetium 99. In seven patients with non-palpable tumours, we used the sentinel node occult lesion localisation (SNOLL) technique. The sentinel node biopsy was examined during surgery, with the frozen section examination and imprint as follows: the sentinel node was cut in three transversal sections along the axis and five frozen sections of each portion were done at a distance of 60 m each; in total, 15-20 frozen sections and three imprints were done for each sentinel node. The axillary dissection was completed in the first 17 patients, and we performed total axillary dissection on the remaining patients if the sentinel node was positive for metastasis.The sentinel nodes were identified in 49 of 50 patients (98%). The patient in whom we did not identify the sentinel node was a patient in the combined technique. The number of nodes identified in the patients with vital dye was one sentinel node, and with the combined technique, it was two sentinel nodes. The false-negative rate was 8% (four patients); the micrometastasis was the principal factor of the false-negative rate (p < 0.05). The cases of false negatives were present at the beginning of the study with the use of the blue dyes; this factor was statistically significant (p < 0.05). The tumour size, the vascular invasion, and the periganglionar adipose tissue invasion were statistically significant for the presentation of axillary metastasis (p < 0.05).This study shows that the micrometastasis and the use of vital dye were the principal factors for the presentation of the false-negative rate. The size of the tumour, the vascular invasion, and the periganglionar adipose tissue invasion were statistically significant for the appearance of the axillary metastasis.
PubMed | Hospital La Linea, Hospital Universitario Of Valme and Complejo Hospitalario Universitario Of Granada
Type: Journal Article | Journal: The Journal of infection | Year: 2015
To assess the incidence of hepatitis C virus (HCV) reinfections after therapy-induced clearance in HIV-coinfected patients with prior chronic hepatitis C.Eighty-four HIV-infected subjects, who had previously achieved sustained virological response (SVR) after being treated of chronic hepatitis C, were analyzed. In all of them, at least yearly HCV RNA determinations were carried out during a median (range) of 34 (12-146) months.Seventy-two (86%) subjects had been people who inject drugs (PWID), of whom 11 (15%) continued to use snorted or injected drugs during the follow-up. Four (4.76%) patients showed HCV reinfection (incidence 1.21 [95% confidence interval: 0.3-3.09] cases per 100 person-years). These patients maintained risk factors for HCV infection. In three cases, HCV genotype switched. Phylogenetic analysis of the remaining case suggested reinfection from his sexual partner.The incidence of HCV reinfection in the overall population of HIV-coinfected patients who achieved SVR after being treated against chronic hepatitis C is low. A low frequency of risk behavior is the main factor accounting for this modest rate of reinfection. The possibility of reinfection should not be considered a reason against treatment of HCV infection with direct acting antivirals in PWID.