Manel Crespo

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.

Raltegravir, etravirine, and ritonavir-boosted darunavir: a safe and successful rescue regimen for multidrug-resistant HIV-1 infection.

Background:Boosted darunavir (DRV/r) plus etravirine (ETR), in DUET trials, and raltegravir, in BENCHMRK trials, showed high rates of virologic response in patients with multidrug-resistant HIV-1 infection, particularly when associated with two more fully active antiretroviral drugs. No data from clinical trials, about this combination, are available. Patients and Methods:Thirty-two consecutive heavily pretreated patients with multidrug-resistant HIV-1 infection who started a new salvage regimen with RAL (400 mg twice daily), ETR (200 mg twice daily), and DRV/r (600/100 mg twice daily) were studied. Clinical evaluation and immunologic, virologic, and biochemical parameters were collected at baseline and at Weeks 4, 12, and 24. Results:Median baseline characteristics were age 44 years, 13 years on antiretroviral therapy, nine prior highly active antiretroviral therapy regimens, 261 CD4 cells/mL, and HIV-1 RNA 4.2 log10 copies/mL. Sixteen (50%) and 14 (44%) patients were enfuvirtide- and tipranavir-experienced, respectively. Three-class resistance mutations were present in all patients. Three patients (9%) had isolates with three ETR resistance mutations. All patients were DRV-naïve with a median of one DRV resistance mutation. At Weeks 4, 12, and 24, respectively, 63%, 81%, and 94% of patients achieved HIV1-RNA less than 50 copies/mL. Median CD4 cell count increased 30, 73, and 103 cells/mL at Weeks 4, 12, and 24, respectively. No patient had adverse events leading to discontinuation of the regimen. Conclusion:The combination of raltegravir, ETR, and DRV/r was a highly effective and well-tolerated antiretroviral salvage regimen in patients infected with multidrug-resistant HIV-1.

Bacterial pneumonia in HIV-infected patients: use of the pneumonia severity index and impact of current management on incidence, aetiology and outcome.

Despite a recent decrease, bacterial pneumonia (BP) is still the most common admission diagnosis in HIV patients. We analyse BP incidence, characteristics and prevention measures.

Acute meningoencephalitis due to human immunodeficiency virus type 1 infection in 13 patients: clinical description and follow-up.

The objective of this study is to describe a series of cases of severe meningitis caused by human immunodeficiency virus type 1 (HIV-1) occurring during primary infection or after antiretroviral treatment interruption. In an observational cohort study, 13 patients with clinical diagnosis of meningitis or meningoencephalitis were reviewed. Ten cases occurred during primary HIV-1 infection and 3 after antiretroviral therapy (ART) withdrawal. Demographic parameters, clinical presentation and outcome, and laboratory and cerebrospinal fluid (CSF) parameters were recorded. The risk factor for HIV-1 infection acquisition was sexual transmission in all cases. The most frequent systemic symptoms were fever (12/13) and headeache (9/13). Among neurologic symptoms, focal signs appeared in seven patients (53.8%), confusion in six (46.2%), and agitation in five (38.5%). The median CD4 cell count was 434 cells/mm3. In all cases, CSF was a clear lymphocytaire fluid with normal glucose levels. Cranial computerized tomography was performed in seven patients, with a normal result in all of them; brain magnetic resonance in eight patients was normal in five cases and showing cortical atrophy, limbic encephalitis, and leptomeningeal enhancement in one patient each. The electroencephalographs (EEG) just showed diffuse dysfunction in three cases. ART was started in 11 patients. HIV RNA load at 12 months was <50 copies/ ml in all treated patients. The 13 patients recovered without neurologic sequela. Meningitis or meningoencephalitis during primary HIV-1 infection or after ART cessation are unusual but sometimes a life-threatening manifestation. Although all patients tend to recover and the necessity of ART is not well established, some data suggest its potential benefit in these patients.

Tratamiento de la neumonía por Legionella pneumophila. ¿Macrolidos o quinolonas?

Antecedentes Los nuevos macrolidos y las fluorquinolonas constituyen actualmente el tratamiento de eleccion de la neumonia por Legionella pneumophila (NLP). El objetivo de nuestro estudio es analizar la eficacia de claritromicina, azitromicina y levofloxacino en el tratamiento de la NLP. Metodos Estudio prospectivo observacional de todos los pacientes adultos diagnosticados de NLP en el Hospital Universitario Vall d’Hebron de Barcelona entre enero de 2001 y diciembre de 2004. Se han comparado variables clinicas evolutivas (duracion de la fiebre, duracion del ingreso hospitalario y mortalidad) entre 52 pacientes tratados con claritromicina, 43 con azitromicina y 18 con levofloxacino. Resultados No se observaron diferencias significativas en cuanto a la presencia de factores de riesgo, porcentaje de pacientes inmunodeprimidos, gravedad inicial de la neumonia o necesidad de ingreso en la unidad de cuidados intensivos entre los pacientes tratados con claritromicina, azitromicina o levofloxacino. La mortalidad hospitalaria fue del 5,3%. No encontramos diferencias significativas con respecto al tiempo que se tardo en conseguir la apirexia, la media de estancia hospitalaria y la mortalidad entre ninguno de los 3 grupos. Conclusion En nuestra experiencia, la eficacia clinica de claritromicina, azitromicina y levofloxacino es similar para el tratamiento de la NLP.

Neurological opportunistic infections and neurological immune reconstitution syndrome: impact of one decade of highly active antiretroviral treatment in a tertiary hospital.

Despite the reported decrease in the incidence and mortality rates of central nervous system (CNS) infections after the introduction of highly active antiretroviral therapy (HAART), few studies have focused on the global incidence and the relationship of these diseases with immune reconstitution inflammatory syndrome (IRIS) in the developed world.

Changes in body composition and mitochondrial DNA in HIV-1-infected patients switching to fixed-dose abacavir/lamivudine or tenofovir/emtricitabine: a substudy of the BICOMBO trial.

BACKGROUNDnFat distribution, bone mineral density (BMD) and mitochondrial DNA (mtDNA) may improve, in the long-term, after switching from nucleoside reverse transcriptase inhibitors (NRTIs) to fixed-dose abacavir (ABC)/lamivudine (3TC) or tenofovir (TDF)/emtricitabine (FTC).nnnMETHODSnThis was a prospective, randomized, open-label, multicentre substudy of the BICOMBO trial in which virologically suppressed patients had their NRTIs switched to ABC/3TC or TDF/FTC. Whole-body dual-energy X-ray absorptiometry (DXA) was used to measure limb, trunk and total body fat and total BMD. Lumbar and hip DXA scans were used to measure lumbar and hip BMD. Fat mass ratio (FMR; % trunk fat/% leg fat by whole-body DXA) was used to assess fat distribution. mtDNA was measured in peripheral blood mononuclear cells (PBMCs). Parameters of interest were measured at baseline, 48 and 96 weeks, and were compared between treatment groups.nnnRESULTSnOf 56 patients included, 45 (20 ABC/3TC and 25 TDF/FTC) completed the substudy. After 96 weeks, ABC/3TC (+756 g, +12.1%) and TDF/FTC (+337 g, +7.6%) led to non-significantly different increases in limb fat (P=0.60). By contrast, trunk fat showed a significant increase (P=0.04) with ABC/3TC (+1,184 g, +10.6%) relative to TDF/FTC (-370 g, -4.2%). Median (IQR) FMR remained unchanged with ABC/3TC (-0.01 [-0.16-0.06]; P=0.23), but it decreased significantly with TDF/FTC (-0.13 [-0.30-0.00]; P=0.007). Total BMD and mtDNA significantly increased after 96 weeks, without differences between groups.nnnCONCLUSIONSnSwitching from NRTIs to either ABC/3TC or TDF/FTC led to similar increases in limb fat, BMD and PBMC mtDNA after 96 weeks.

The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men.

Electrocautery is one of the main treatment options for high‐grade anal intraepithelial neoplasia (HGAIN). However, data regarding its efficacy are scarce. The aim of the study was to evaluate the effectiveness of electrocautery for the treatment of HGAIN.

Liver stiffness and aspartate aminotransferase levels predict the risk for liver fibrosis progression in hepatitis C virus/HIV‐coinfected patients

The aim of the study was to investigate liver fibrosis outcome and the risk factors associated with liver fibrosis progression in hepatitis C virus (HCV)/HIV‐coinfected patients.

Hyperkalemic Distal Renal Tubular Acidosis Caused by Immunosuppressant Treatment with Tacrolimus in a Liver Transplant Patient: Case Report

Nephrotoxicity is one of the most common side effects of long-term immunosuppressive therapy with calcineurin inhibitors. We describe a case of distal renal tubular acidosis secondary to tacrolimus administration. A 43-year-old man with end-stage liver disease due to hepatitis C and B virus infections and alcoholic cirrhosis received a liver transplantation under immunosuppressive treatment with tacrolimus and mycophenolate mofetil. In the postoperative period, the patient developed hyperkalemic hyperchloremic metabolic acidosis, with a normal serum anion gap and a positive urinary anion gap, suggesting distal renal tubular acidosis. We excluded other causes of hyperkalemia. Administration of intravenous bicarbonate, loop diuretics, and oral resin exchanger corrected the acidosis and potassium levels. Distal renal tubular acidosis is one of several types of nephrotoxicity induced by tacrolimus treatment, resulting from inhibition of potassium secretion in the collecting duct. Treatment to correct the acidosis and hyperkalemia should be promptly initiated, and the tacrolimus dose adjusted when possible.