Jordi Niubó

Less lipoatrophy and better lipid profile with abacavir as compared to stavudine: 96-week results of a randomized study.

Objective:To assess lipoatrophy, other toxicities, and efficacy associated with abacavir as compared with stavudine in HIV-infected antiretroviral-naive patients. Methods:This was a prospective, randomized, open trial, stratified by viral load and CD4 cell count, conducted January 2001 to July 2004. Two hundred thirty-seven adult patients with HIV infection initiating antiretroviral therapy were assigned to receive abacavir (n = 115) or stavudine (n = 122), both combined with lamivudine and efavirenz. The primary endpoint was the proportion of patients with lipoatrophy as assessed by physician and patient observation at 96 weeks. Results:A lower proportion of patients assigned to abacavir developed clinical signs of lipoatrophy (4.8% vs. 38.3%; P < 0.001). These observations were confirmed by anthropometric data. Dual energy x-ray absorptiometry (DEXA) scans performed in 57 patients showed significantly greater total limb fat loss in the stavudine arm (−1579 vs. 913 g; P < 0.001). The lipid profile in abacavir patients presented more favorable changes in the levels of triglycerides (P = 0.03), high-density lipoprotein cholesterol (HDLc; P < 0.001), and apolipoprotein A1 (P < 0.001) as well as in the ratio between total cholesterol and HDLc (P = 0.005). Throughout the study, a higher proportion of patients in the stavudine group received lipid-lowering agents as compared to the abacavir group (17% vs. 4%; P = 0.002). Similar virologic and immunologic responses were observed. Conclusions:Assuming the limitations inherent to clinical assessment, this study shows a notably weaker association of abacavir with lipoatrophy than stavudine. DEXA scans and anthropometric measurements supported the clinical findings. In addition, the lipid changes that occurred were more favorable in patients receiving abacavir.

Viral infections of the central nervous system in Spain: A prospective study

The aim of the study was to determine the incidence of viruses causing aseptic meningitis, meningoencephalitis, and encephalitis in Spain. This was a prospective study, in collaboration with 17 Spanish hospitals, including 581 cases (CSF from all and sera from 280): meningitis (340), meningoencephalitis (91), encephalitis (76), febrile syndrome (7), other neurological disorders (32), and 35 cases without clinical information. CSF were assayed by PCR for enterovirus (EV), herpesvirus (herpes simplex [HSV], varicella‐zoster [VZV], cytomegalovirus [CMV], Epstein–Barr [EBV], and human herpes virus‐6 [HHV‐6]), mumps (MV), Toscana virus (TOSV), adenovirus (HAdV), lymphocytic choriomeningitis virus (LCMV), West Nile virus (WNV), and rabies. Serology was undertaken when methodology was available. Amongst meningitis cases, 57.1% were characterized; EV was the most frequent (76.8%), followed by VZV (10.3%) and HSV (3.1%; HSV‐1: 1.6%; HSV‐2: 1.0%, HSV non‐typed: 0.5%). Cases due to CMV, EBV, HHV‐6, MV, TOSV, HAdV, and LCMV were also detected. For meningoencephalitis, 40.7% of cases were diagnosed, HSV‐1 (43.2%) and VZV (27.0%) being the most frequent agents, while cases associated with HSV‐2, EV, CMV, MV, and LCMV were also detected. For encephalitis, 27.6% of cases were caused by HSV‐1 (71.4%), VZV (19.1%), or EV (9.5%). Other positive neurological syndromes included cerebellitis (EV and HAdV), seizures (HSV), demyelinating disease (HSV‐1 and HHV‐6), myelopathy (VZV), and polyradiculoneuritis (HSV). No rabies or WNV cases were identified. EVs are the most frequent cause of meningitis, as is HSV for meningoencephalitis and encephalitis. A significant number of cases (42.9% meningitis, 59.3% meningoencephalitis, 72.4% encephalitis) still have no etiological diagnosis. J. Med. Virol. 85:554–562, 2013.

West Nile virus in Spain : Report of the first diagnosed case (in Spain) in a human with aseptic meningitis

We report the first case of illness caused by West Nile virus (WNV) so far diagnosed in Spain. A 21-y-old male presented with clinical and biological signs compatible with viral meningitis. Acute and convalescent serum samples showed IgM and IgG positivity for WNV. These results were confirmed by microneutralization assays.

Association of quantitative cytomegalovirus antigenemia with symptomatic infection in solid organ transplant patients

A prospective virologic follow-up of solid organ transplant patients was designed to determine the usefulness of antigenemia and viremia as virologic markers for the diagnosis of cytomegalovirus (CMV) infections, and also for monitoring CMV disease and therapy control. A total of 629 blood samples from 127 patients (60 liver, 47 kidney, and 20 heart transplant recipients) were studied by tube and shell vial cultures, and by antigenemia assay. This later was carried out by an indirect immunofluorescent assay method for formalin-fixed cytospin slides containing 2 x 10(5) leukocytes, using a monoclonal antibody directed against the CMV pp65 antigen. CMV was detected by at least one of the three methods in 238 specimens (37.8%) from a total of 63 patients. The antigenemia assay was positive in 215 (90.3% of positive samples). A total of 94 samples were detected only by this marker, which occurred either in samples with low positive counts (70.2% with antigenemia counts < 10 positive cells/10(5) leukocytes) or in specimens from treated patients. There were 30 episodes of CMV disease in 23 patients. Antigenemia was positive in all these episodes, 27 of them with counts > 20 positive cells/10(5) leukocytes. With this cut-off, positive and negative predictive values for symptomatic CMV infection were 100% and 97.2%, respectively. The antigenemia assay is a rapid, sensitive, specific, and early marker of CMV infection in transplantees. Cultures became negative with antiviral therapy while remaining antigenemia detectable. There was an association between highest quantitative antigenemia test results and clinical symptoms in our patients. In its quantitative version, the assay is useful to detect symptomatic infection and appears to be a helpful tool in managing patients at risk and in guiding antiviral therapy.

Maraviroc Concentrations in Cerebrospinal Fluid in HIV-Infected Patients

Objective:To determine maraviroc (MVC) concentrations in cerebrospinal fluid (CSF) in HIV-infected patients. Methods:Twelve CCR5+ HIV-1 adult antiretroviral-experienced patients receiving MVC-containing regimens for at least 1 month were enrolled. Both CSF and blood samples were taken around 12 hours after the last MVC dose. liquid chromatography tandem mass spectrometry was used to determine MVC concentrations, and HIV-1 viral load was determined by real-time polymerase chain reaction, (LOD, 40 copies/mL). Results:Twelve blood and 12 CSF samples were collected. Median CD4 count was 281(120-759) cells per microliter, and median HIV-1 viral load was <40 copies per milliliter. Median time on MVC was 13.5 weeks (4-60). Nucleoside analogues (tenofovir/didanosine) were given in only 1 case. Median MVC concentrations in plasma were 124.75 (7.3-517) ng/mL. In all except one, CSF sample-receiving an erroneous MVC dose while taking concomitantly nevirapine-MVC concentrations [2.58 (<0.5-7.22) ng/mL] were within the EC90 range (0.06-10.70). Median MVC CSF: plasma ratio was 0.022 (0.004-0.17), and when the free MVC plasma concentration was used, 0.094 (2.58-27.44). CSF viral load was <40 copies per milliliter in all 9 patients with undetectable plasma viral load. Conclusions:MVC achieves concentrations within the EC90 range in CSF. All patients with undetectable plasma viral load although receiving nucleoside-sparing regimens including new drugs showed viral suppression in CSF.

Prophylaxis versus preemptive therapy for cytomegalovirus disease in high‐risk liver transplant recipients

Cytomegalovirus (CMV) infection is an opportunistic infection frequently found after solid organ transplantation, and it contributes significantly to mortality and morbidity. CMV‐seronegative recipients of grafts from CMV‐seropositive donors have the highest risk of CMV disease. The most appropriate strategy for preventing CMV disease in this population is a matter of active debate. In this study, we compared prophylaxis and preemptive therapy for the prevention of CMV disease in donor‐seropositive/recipient‐seronegative (D+/R−) liver recipients. To this end, we selected a retrospective cohort of liver recipients (1992‐2009) for analysis. D+/R− patients were identified from the liver transplant program database. Eighty of 878 consecutive liver recipients (9%) were D+/R−. Six of these patients died within 30 days of transplantation and were excluded. Thirty‐five of the remaining D+/R− patients (47%) received prophylaxis, and 39 patients (53%) followed a preemptive strategy based on CMV antigenemia surveillance. Fifty‐four (73%) were men, the median age was 49 years (range = 15‐68 years), and the mean follow‐up was 68 months (range = 8‐214 months). The baseline characteristics and the initial immunosuppressive regimens were similar for the 2 groups. Ganciclovir or valganciclovir was the antiviral drug used initially in both strategy groups. CMV disease occurred more frequently among D+/R− liver recipients receiving preemptive therapy (33.3% versus 8.6% for the prophylaxis group, P = 0.01), whereas late‐onset CMV disease was found only in patients receiving prophylaxis (5.7% versus 0% for the preemptive therapy group, P = 0.22). No significant differences in acute allograft rejection, other opportunistic infections, or case fatality rates were observed. According to our data, prophylaxis was more effective than preemptive therapy in preventing CMV disease in high‐risk liver transplant recipients. Liver Transpl, 2012.

Etravirine concentrations in CSF in HIV-infected patients

OBJECTIVES To determine etravirine concentrations in CSF in HIV-infected patients. METHODS Twelve HIV-1 adult antiretroviral-experienced patients receiving an etravirine-containing regimen for at least 1 month were enrolled. Both CSF and blood samples were taken around 12 h after the last etravirine dose. Liquid chromatography-tandem mass spectrometry was used to determine etravirine concentrations, and HIV-1 viral load was determined by real-time PCR (limit of detection 40 copies/mL). RESULTS Twelve blood and 12 CSF samples were collected. The median CD4 count was 333 (84-765) cells/mm(3) and the median plasma HIV-1 viral load was <40 (range <40-1777) copies/mL. The median time on etravirine was 34 (range 4-140) weeks. The median etravirine concentration in plasma was 611.5 (range 148-991) ng/mL. The median CSF etravirine concentration was 7.24 (range 3.59-17.9) ng/mL; in all cases, values were above the IC(50) range (0.39-2.4 ng/mL). The median etravirine CSF:plasma ratio was 0.01 (range 0.005-0.03). The CSF viral load was >40 copies/mL in one patient and plasma viral load was still detectable after 4 weeks of therapy. CONCLUSIONS Etravirine achieves concentrations several times greater than the IC(50) range in CSF. All patients with undetectable plasma viral load were virologically suppressed in CSF while receiving an etravirine-containing regimen. Etravirine may help in controlling HIV-1 in CNS.

Successful outcome of ganciclovir-resistant cytomegalovirus infection in organ transplant recipients after conversion to mTOR inhibitors.

Ganciclovir‐resistant (GanR) cytomegalovirus (CMV) infection after organ transplantation is emerging as a significant therapeutic challenge. We report two cases of GanR CMV infection successfully managed by switching immunosuppression from calcineurin inhibitors to an mTOR inhibitor‐based regimen. This salvage therapy should be considered when other options are not available.

pp65 antigenemia as a marker of future CMV disease and mortality in HIV-infected patients.

We retrospectively evaluated the role of pp65 antigenemia (AGM) as a marker of cytomegalovirus (CMV) disease and mortality in 241 HIV-infected patients with fever. Of 225 patients in whom CD4 count was available, 189 (84%) had counts below 100/microL and 209 (92.8%) below 200/microL, 149 patients had negative AGM (AGM-) and 92 had positive AGM (AGM+), AGM+ patients were at a more advanced stage of HIV disease, as evaluated by CD4 count (p < 0.001) and prior AIDS diagnosis (p < 0.001). Overall, 29 patients (12%) presented concomitant CMV disease (18 retinitis): 24 (26%) in the AGM+ group and 5 (3.3%) in the AGM- group (p < 0.001). AGM had a negative predictive value of 96.6% but a positive predictive value of 26% which increased to 65% if a cut-off of > 10 CMV-positive cells/10(5) leukocytes was considered. The cumulative rate of future CMV disease at 3 months was 0% in AGM patients, 3% in patients with AGM 1-10/10(5) and 36% in patients with AGM > 10/10(5). In a multivariate analysis, no antiretroviral therapy, AGM+ and CMV disease were independently associated with mortality. The role of AGM as a marker of present CMV disease is limited. However, quantitative AGM may select patients at a high risk of future CMV disease. In addition, AGM may be a marker of shorter survival in severely immunosuppressed HIV-infected patients.

Community-acquired pneumonia during the first post-pandemic influenza season: A prospective, multicentre cohort study

Summary Objectives To determine the aetiology, clinical features and prognosis of CAP during the first post-pandemic influenza season. We also assessed the factors associated with severe disease and tested the ability of a scoring system for identifying influenza A (H1N1)pdm09-related pneumonia. Methods Prospective cohort study carried out at 10 tertiary hospitals of Spain. All adults hospitalised with CAP from December 01, 2010 to March 31, 2011 were analysed. Results A total of 747 adults with CAP required hospitalisation. The aetiology was determined in 315 (42.2%) patients, in whom 154 (21.9%) were due to bacteria, 125 (16.7%) were due to viruses and 36 (4.8%) were mixed (due to viruses and bacteria). The most frequently isolated bacteria were Streptococccus pneumoniae. Among patients with viral pneumonia, the most common organism identified were influenza A (H1N1)pdm09. Independent factors associated with severe disease were impaired consciousness, septic shock, tachypnea, hyponatremia, hypoxemia, influenza B, and influenza A (H1N1)pdm09. The scoring system evaluated did not differentiate reliably between patients with influenza A (H1N1)pdm09-related pneumonia and those with other aetiologies. Conclusions The frequency of bacterial and viral pneumonia during the first post-pandemic influenza season was similar. The main identified virus was influenza A (H1N1)pdm09, which was associated with severe disease. Although certain presenting clinical features may allow recognition of influenza A (H1N1)pdm09-related pneumonia, it is difficult to express them in a reliable scoring system.