Esteve Ribera

Invasive Pneumococcal Disease in Patients Infected with HIV: Still a Threat in the Era of Highly Active Antiretroviral Therapy

We studied all human immunodeficiency virus (HIV)-infected patients with invasive pneumococcal disease who received their diagnosis during 1996-2002 to investigate the incidence of this disease in the highly active antiretroviral therapy era and to study the influence of CD4 lymphocyte count on the clinical presentation and outcome of disease. The overall incidence of invasive pneumococcal disease was 11.3 cases per 100,000 person-years in adult patients without known HIV infection and 677 cases per 100,000 person-years in HIV-infected patients. This incidence remained stable over the study period. Clinical presentation, severity of illness, and number of recurrent episodes were similar in patients with CD4+ cell counts of >200 or < or =200 cells/ microL. Patients receiving trimethoprim-sulfamethoxazole (TMP-SMZ) were more likely to present with TMP-SMZ-resistant pneumococci than were those who were not receiving this agent (76.7% vs. 43.6%; P=.007). The mortality rate was high (21%).

Unexpected CD4 cell count decline in patients receiving didanosine and tenofovir-based regimens despite undetectable viral load.

Background: We recently observed a significant CD4 cell count decline in patients receiving didanosine (ddI) 400 mg, tenofovir (TDF) and nevirapine (NVP), despite virological suppression. Methods: We identified from our computerized patient database subjects who initiated combinations containing ddI and/or TDF for reasons other than virological failure, including simplification or intolerance. Changes in total, CD4+ and CD8+ lymphocyte counts since the initiation of therapy were analysed retrospectively. Plasma concentration of ddI was prospectively determined in eight of these patients receiving ddI 400 mg + TDF + NVP and 3 weeks after a ddI dosage reduction. Results: A total of 302 patients were studied. A significant decrease in CD4 and CD8 and in total lymphocyte counts was only seen in subjects receiving ddI standard dose + TDF-containing regimens, despite the maintenance of viral suppression. More than 50% of these patients showed a decline of more than 100 CD4 cells at 48 weeks. In contrast, subjects not receiving ddI + TDF together experienced the expected progressive increase in CD4 T-cell counts. Plasma levels of ddI were elevated in all patients receiving the standard ddI dose + TDF. DdI plasma levels significantly decreased when patients weighting > 60 kg reduced ddI dose to 250 mg, achieving similar levels to those generated by ddI 400 mg without TDF. Conclusions: Co-administration of ddI at standard doses plus TDF appears to exert a deleterious effect on CD4 and CD8 counts. Although lymphocyte toxicity related to excessive ddI plasma levels could explain our findings, other mechanisms cannot be excluded. Pharmacokinetic data suggest ddI dose reduction when coadministered with TDF.

Prophylaxis of visceral leishmaniasis in human immunodeficiency virus-infected patients

OBJECTIVE To assess the effectiveness of two regimens with allopurinol or pentavalent antimony as secondary prophylaxis for visceral leishmaniasis (VL) in human immunodeficiency virus (HIV)-infected patients. DESIGN Retrospective, nonrandomized, open trial. SETTING A 1,000-bed academic tertiary institutional hospital in Barcelona. PATIENTS Forty-six individuals over 14 years old with HIV infection, who recovered from an episode of VL between January 1988 and February 1995. INTERVENTIONS Twenty patients did not receive any prophylaxis, nine received 300 mg/8 h of allopurinol, and 17 received 850 mg once-a-month of pentavalent antimony. Patients were followed-up every 3 months, and the endpoint of study was relapse of VL. RESULTS Twenty-one patients had recurrent VL: 13 of 20 in the control group (65%), 5 of 9 in the allopurinol group (56%), and 3 of 17 in the antimonial group (18%). Kaplan-Meier estimates of the probability of remaining relapse-free at 12 months were 9% without prophylaxis (95% CI, 0-22%), 21% with allopurinol (95% CI, 0-51%), and 93% with antimonials (95% CI, 82-100%) (P < 0.001). Multivariate analysis showed that the only significant variables related to relapsing course of VL were assignment to the antimonial group, and the fact that the patient had experienced a previous episode of VL. CONCLUSIONS Pentavalent antimony given once a month is effective in the prevention of VL relapses in HIV-infected individuals. It is a low-cost treatment that proved to be well tolerated. Therefore, pentavalent antimony should be considered a suitable agent for secondary prophylaxis against VL.

Randomized trial comparing ceftriaxone with cefonicid for treatment of spontaneous bacterial peritonitis in cirrhotic patients.

We compared cefonicid (2 g every 12 h) and ceftriaxone (2 g every 24 h) for their efficacy and safety in treating spontaneous bacterial peritonitis in cirrhotic patients in an open randomized clinical trial (30 patients in each group). Clinical, laboratory, and bacteriologic characteristics were similar in both groups. Ceftriaxone-susceptible strains were isolated on 44 occasions (94%), and cefonicid-susceptible strains were isolated on 43 occasions (91.5%). The antibiotic concentration in ascitic fluid/MIC ratio for ceftriaxone was > 100 throughout the dose interval (24 h), while it was lower for cefonicid (between 1 and 18). A total of 100% of patients treated with ceftriaxone, and 94% of those treated with cefonicid were cured of their infections (P was not significant). Hospitalization mortality was 37% in the cefonicid group and 30% in the ceftriaxone group (P was not significant). The time that elapsed between the initiation of treatment and the patients death was shorter in the cefonicid group patients (5.3 +/- 3.90 days) than in the ceftriaxone group patients (11.8 +/- 9.15 days) (P < 0.05). None of the patients presented with superinfections, and only two patients treated with cefonicid and three patients treated with ceftriaxone developed colonizations with Enterococcus faecalis or Candida albicans. Ceftriaxone and cefonicid are safe and useful agents for treating cirrhotic spontaneous bacterial peritonitis, although the pharmacokinetic characteristics of ceftriaxone seem to be more advantageous than those of cefonicid.

Efficacy and safety of switching from boosted lopinavir to boosted atazanavir in patients with virological suppression receiving a LPV/r-containing HAART: the ATAZIP study.

Objectives:To evaluate the efficacy and safety of switching from boosted lopinavir (LPV/r) to boosted atazanavir (ATV/r) in virologically suppressed HIV-1-infected patients versus continuing LPV/r. Methods:Forty-eight weeks analysis of a randomized, open-label, noninferiority trial including patients with virological suppression (≤200 copies/mL for ≥6 months) on LPV/r-containing triple highly active antiretroviral therapy. Patients (n = 248) were randomized 1:1 either to continue LPV/r twice a day (n = 127) or to switch to ATV/r every day (ATV/r; n = 121), with no change in nucleoside reverse transcriptase inhibitor backbone. Those known to have >4 protease inhibitor (PI)-associated mutations and/or who had failed >2 PI-containing regimens were excluded. Results:Baseline characteristics were balanced. 30% harboured ≥1 PI-associated mutation (10% harboured ≥1 major mutation). Treatment failure at 48 weeks (primary end point) occurred in 20% (25 of 127) of the LPV/r arm and in 17% (21 of 121) of the ATV/r arm (difference −2.3%; 95% confidence interval: −12.0 to 8.0; P = 0.0018). Virological failure occurred in 7% (9 of 127) of the LPV/r arm and in 5% (6 of 121) of the ATV/r arm (difference −2.1%; 95% confidence interval: −8.7% to 4.2%, P < 0.0001 for noninferiorating). CD4+ changes from baseline were similar in each arm (approximately 40 cells/mm3). Adverse event rate leading to study drug discontinuation was 5% in both arms. Median fasting triglycerides and total cholesterol decreased significantly in the ATV/r arm (−53 and −19 mg/dL, respectively versus −4 and −4 mg/dL in the LPV/r arm; P < 0.001 in both comparisons). Alanine aminotransferase/aspartate aminotransferase hepatic abnormalities were similar in the 2 arms. Conclusions:Switching to ATV/r in virologically suppressed patients who were receiving a LPV/r-containing highly active antiretroviral therapy provided comparable (noninferior) efficacy and a safety profile with improved lipid parameters [ISRCTN24813210].

Recomendaciones de GESIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en pacientes adultos infectados por el VIH (octubre 2004)

Objetivo Efectuar una puesta al dia de las recomendaciones sobre el tratamiento antirretroviral (TAR) para los adultos infectados por el virus de la inmunodeficiencia humana (VIH). Metodos Estas recomendaciones se han consensuado por un comite del Grupo de Estudio de Sida (GESIDA) y del Plan Nacional sobre el Sida (PNS). Para ello se han revisado los avances en la fisiopatologia del VIH, los resultados de eficacia y seguridad de ensayos clinicos, estudios de cohortes y de farmacocinetica, publicados en revistas biomedicas o presentados en congresos en los ultimos anos. Se han definido tres niveles de evidencia segun la procedencia de los datos: estudios aleatorizados (nivel A), de cohortes o de caso-control (nivel B), u opinion de expertos (nivel C). En cada una de las situaciones se ha establecido recomendar, considerar o no recomendar el TAR. Resultados En el momento actual, el TAR con combinaciones de al menos tres farmacos constituye el tratamiento de inicio de eleccion de la infeccion cronica por el VIH. Estas pautas deben incluir dos inhibidores de la transcriptasa inversa analogos de nucleosidos (ITIAN) mas un no nucleosido (ITINN) o dos ITIAN mas un inhibidor de la proteasa (IP). En los pacientes con una infeccion por VIH sintomatica se recomienda iniciar TAR. En los pacientes asintomaticos el inicio de TAR se basara en la cifra de linfocitos CD4+/μl y en la carga viral plasmatica (CVP): a) en pacientes con linfocitos CD4+ 350 cel./μl se puede diferir el inicio del TAR. El objetivo del TAR inicial es lograr una CVP indetectable. La adherencia al TAR tiene un papel fundamental en la duracion de la respuesta antiviral. Las opciones terapeuticas en los fracasos del TAR son limitadas por la aparicion de resistencias cruzadas. Los estudios genotipicos en estos casos son de utilidad. La toxicidad es un factor limitante del TAR, aunque los beneficios superan los posibles perjuicios. Tambien se discuten los criterios de TAR de la infeccion aguda, embarazo y profilaxis postexposicion, y el manejo de la coinfeccion por el VIH y los virus de la hepatitis C y B (VHC y VHB). Conclusiones La cifra de linfocitos CD4+ es el factor de referencia mas importante para iniciar el TAR en pacientes asintomaticos. Por otra parte, el numero considerable de farmacos disponibles, los metodos de monitorizacion mas sensibles (CVP), y la posibilidad de determinar las resistencias hacen que las estrategias terapeuticas sean mucho mas individualizadas.

Evaluation of a latex agglutination test (KAtex) for detection of Leishmania antigen in urine of patients with HIV-Leishmania coinfection: value in diagnosis and post-treatment follow-up

The usefulness of antigen detection in urine as an alternative tool for diagnosis of leishmaniasis and post-treatment follow-up in patients with Leishmania-HIV coinfection was evaluated with a latex agglutination test (KAtex; Kalon Biological, UK). Forty-nine HIV-infected patients with visceral leishmaniasis were included in the study. Antigen detection in urine (ADU) was positive in 42 of 49 (sensitivity, 85.7%) samples obtained during a primary episode. After treatment, a follow-up study in 23 patients was performed by simultaneous ADU and culture of peripheral blood mononuclear cells in 148 determinations. The two methods gave concordant results in 94 cases, 38 of which were positive and 56 negative. In five cases, ADU was negative and culture of peripheral blood mononuclear cells was positive: two of these cases corresponded to clinical relapses. In 49 cases, culture of peripheral blood mononuclear cells was negative and ADU was positive. In the absence of clinical symptoms, the detection of parasite antigens in 71 of 130 (54.6%) urine samples was not associated with clinical disease. The Kaplan-Meier estimates of the probability of relapse at 6, 12, 18, and 24 months were 16% (95%CI, 15–17%), 20% (95%CI, 18–22%), 31% (95%CI, 27–35%), and 71% (95%CI, 52–89%), respectively, in patients with a positive ADU result. In contrast, when ADU was negative, the probability of relapse was 5% at 6 months (95%CI, 2–8%) (only 2 of 11 patients who relapsed had a negative test). ADU by KAtex is appropriate for primary diagnosis of visceral leishmaniasis, for monitoring the efficacy of treatment, and for detection of subclinical infection.

Effectiveness of Polysaccharide Pneumococcal Vaccine in HIV-Infected Patients: a Case-Control Study

BACKGROUND Polysaccharide pneumococcal vaccine (PPV) is recommended among human immunodeficiency virus (HIV)-infected patients, although its effect in reducing the incidence of pneumonia or invasive pneumococcal disease is not well established. Our objective was to determine the effectiveness of 23-valent PPV in HIV-infected adults and the risk factors for pneumococcal pneumonia or invasive pneumococcal disease. METHODS We performed a retrospective case-control study in 4 Spanish hospitals for the period from January 1995 through December 2005 using the HIV database from each hospital to identify case patients with Streptococcus pneumoniae disease and control subjects without a history of pneumococcal infection. RESULTS A total of 184 case patients and 552 control subjects were identified. The factors associated with pneumococcal disease in bivariate analysis were active injection drug use (odds ratio [OR], 3.33; 95% confidence interval [CI], 2-5.55), alcoholism (OR, 3.03; 95% CI, 1.86-4.91), chronic obstructive pulmonary disease (OR, 2.58; 95% CI, 1.3-5.1), cirrhosis (OR, 6.05; 95% CI, 3.2-11.4), antiretroviral therapy (OR, 0.23; 95% CI, 0.16-0.32), trimethoprim-sulfamethoxazole prophylaxis (OR, 0.66; 95% CI, 0.45-0.97), viral load <5000 copies/mL (OR, 0.38; 95% CI, 0.26-0.54), and previous PPV (OR, 0.39; 95% CI, 0.24-0.65). Risk factors for pneumococcal disease in multivariate analysis were cirrhosis (OR, 5.64; 95% CI, 2.53-12.53), chronic obstructive pulmonary disease (OR, 2.90; 95% CI, 1.21-6.94), and alcoholism (OR, 2.15; 95% CI, 1.11-4.19), whereas protective factors were receipt of antiretroviral therapy (OR, 0.23; 95% CI, 0.14-0.36) and receipt of pneumococcal vaccine (OR, 0.44; 95% CI, 0.22-0.88), even in patients with CD4 lymphocyte counts <200 cells/microL. CONCLUSIONS Antiretroviral therapy and PPV have a significant, independent protective effect against pneumococcal disease, regardless of CD4 lymphocyte count; thus, all patients with HIV infection should be vaccinated with PPV to prevent pneumococcal disease.

A nested polymerase chain reaction for diagnosis and follow-up of human visceral leishmaniasis patients using blood samples

A nested polymerase chain reaction (PCR) assay for the diagnosis of human visceral leishmaniasis (VL) due to Leishmania infantum infection was developed using primers selected from the parasites genomic deoxyribonucleic acid (DNA). The assay, which is based on the use of leucocytes separated from blood samples by Ficoll-Paque centrifugation, was compared with culture in vitro. Blood samples were collected from 17 patients in Spain with a history of clinical VL, 15 of whom were also infected with human immunodeficiency virus (HIV) (13 samples during the VL episode and 31 samples during post-treatment monitoring) and one sample was collected from each of 28 patients with HIV infection and fever but no history of VL. The nested PCR using blood detected all the cases of parasitologically confirmed, clinically active VL, while culture detected 92%. The nested PCR detected Leishmania DNA in 18% of the HIV-infected patients with fever and no history of VL, none of whom gave a positive culture. Follow-up examination of the VL patients by nested PCR and culture demonstrated the persistence of L. infantum in blood for a long time after treatment.

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.