Ricardo Rabagliati

HIV infection, HAART, and endothelial adhesion molecules: current perspectives

In this review we summarise the data on the effects of HIV infection and its therapy with antiretroviral drugs on adhesion molecules, considered to be potential biomarkers of endothelial cell function. This is a recent area of interest, given the unexpected associations between antiretroviral therapy, metabolic alterations of lipid profile, and the risk of cardiovascular disease in the absence of clear pathogenetic links. Although convincing prospective data are still scarce, it seems timely to elucidate the potential value of non-invasive, inexpensive tests for predicting cardiovascular risk in HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Endothelial function, the most plausible link between infection, inflammation, and atherosclerosis, has been investigated since the beginning of the HIV epidemic. Increased concentrations of soluble adhesion molecules, such as those from the selectin and immunoglobulin families, have consistently been reported in HIV-positive patients. The introduction of HAART has renewed interest in the study of endothelial function in HIV-positive patients, in view of some HAART-related metabolic abnormalities (hyperlipidaemia, hyperglycaemia, fat redistribution) and several large reports of premature coronary artery disease. Whether HAART reduces endothelial injury associated with HIV infection or contributes to further endothelial cell activation is still a matter of controversy. Also unclear is whether HAART acts directly or indirectly, and if protease inhibitors and other classes of antiretroviral drugs differ in their proatherosclerotic effects. This article attempts to define the state of these emerging issues, identifies areas of controversy and of potential clinical relevance, and suggests some directions for future research.

Older age does not influence CD4 cell recovery in HIV-1 infected patients receiving Highly Active Anti Retroviral Therapy

BackgroundDiagnosis of HIV infection is recently occurring with increasing frequency in middle-aged and in older individuals. As HAART became available, a minimal beneficial effect on immunological outcome in older in respect of younger subjects has been reported. In fact, both the intensity and the rapidity of the immunological response appeared to be reduced in elderly subjects. On the contrary, only few reports have indicated a similar immunological outcome both in older and younger HIV-positive subjects. Interestingly, older age did not seem to significantly affect the long-term virological outcome of HAART treated subjects.MethodsTo characterise epidemiological and clinical features of older HIV+ subjects, a prospective case-control study was performed: 120 subjects ≥ 50 and 476 between 20 and 35 years were initially compared. Subsequently, to better define the impact of HAART on their viro-immunological response, 81 older were compared with 162 younger subjects.ResultsAt baseline cases presented significantly lower TCD4+ cell number and were more frequently affected by comorbid conditions. Under HAART a statistically significant increase in TCD4+ cell number was observed in cases and controls. At multivariate analysis, there was no statistically significant difference between cases and controls regarding viro-immunological response.ConclusionsAlthough older subjects present a more severe HIV infection, they can achieve, under HAART, the same viro-immunological success as the younger individuals.

Endemic scrub typhus-like illness, Chile.

TOC Summary: Rickettsiae closely related to the scrub typhus agent are present in the Western Hemisphere.

Impact of Highly Active Antiretroviral Therapy (HAART) on the Incidence of Bacterial Infections in HIV-Infected Subjects

Abstract The aim of this study was to evaluate the effect of highly active antiretroviral therapy (HAART) on the incidence of bacterial infections in HIV-infected patients. Two time periods were compared: (A) January 1992-December 1995 (before HAART) and (B) January 1997-December 2000 (after HAART). During the study periods, we observed 931 patients with bacterial infections, i.e. 322 with bacter-emia, 369 with bacterial pneumonia and 240 with urinary tract infections, out of 4,242 HIV-infected subjects admitted to the Department of Infectious Diseases of a large university hospital. By comparing the overall incidence of bacterial infections during periods A and B, a statistically significant difference, from 32% to 18% (p<0.01), was observed. Analysis of risk factors of community- and hospital-acquired bacterial infections did not significantly differ in the two study periods. This study establishes that a significant reduction in bacterial infection incidence occurred in HIV-infected subjects when HAART became the standard therapy for HIV infection.

Pandemic influenza A (H1N1) in HIV-1-infected patients.

Objective:To characterize the clinical presentation, course and mortality of pandemic influenza in HIV-1-infected patients in Santiago, Chile. Methods:Prospective observational study. Results:Thirty patients were included (three hospitalized), 93% were on HAART, mean CD4+ cell count was 423 cells/μl and viral load was undetectable in 77% of patients. All patients had fever, 90% had cough, 80% had myalgias, 70% had pharyngeal congestion, 47% had coryza, 47% had odynophagia, 37% had headache and 23% had vomiting. Four patients developed pneumonia. All patients received antiviral therapy and no patient died. Conclusions:HIV patients infected by the new influenza A pandemic (H1N1) virus behave similarly to the general population.

Prevalence of tuberculosis and its impact on mortality among HIV infected patients in Chile

BACKGROUND Tuberculosis (TB) in Chile is reaching the elimination phase; however, in HIV positive individuals the incidence of TB in still very high. AIM To describe the association between TB and HIV in different geographical regions in Chile, and to determine the association between TB and HIV/AIDS mortality. PATIENTS AND METHODS A retrospective study that included individuals from the main HIV clinics from four regions with different TB prevalence in the general population (per 100,000): Arica (>30), Concepcion/Arauco (25-29), Valparaiso/San Antonio (20-24) and Metropolitana Sur-Oriente (SSMSO) (<20), attended between January 1998 and September 2004. RESULTS Nine hundred and twelve HIV positive individuals were included. Global prevalence of TB was 6.2% [95% confidence intervals (Cl) 5.2-7.2%]. TB was more common in older subjects (p =0.039) and those with lower CD4 counts (p <0.001) and higher HIV viral load (p =0.033). In 66% of cases, the disease had a pulmonary localization. TB was the recorded cause of death in 7.4% of subjects. Only 29% of patients had a tuberculin skin test performed at the moment of HIV diagnosis. The prevalence of TB in HIV positive patients, followed the trend of TB prevalence in the general population: Concepcion/Arauco (11.9%), Valparaiso/San Antonio (7.1%) and SSMSO (3.9%). However HIV positive subjects from Arica showed an unexpectedly low TB prevalence (5.5%). CONCLUSIONS TB in HIV/AIDS patients included in this study is over 300 times more prevalent than in the general population. TB prevalence in HIV positive subjects follows regional TB prevalence, excepting Arica. Effectiveness and feasibility of latent TB diagnostic strategies and treatment in HIV positive individuals should be reviewed.

Características clínicas, diagnósticas y pronosticas de pacientes con neumonía por Pneumocystis jiroveci en individuos infectados por virus de inmunodeficiencia humana e individuos inmunocomprometidos por otra etiología: comparative study of cases in HIV-infected patients and immunocompromised non-HIV-infected patients

Introduccion: Pneumocystis jiroveci puede causar neumonia en pacientes inmunocomprometidos de cualquier etiologia, pero las diferencias clinicas y pronosticas entre inmunocomprometidos por VIH y por otras causas han sido poco exploradas. Objetivo: Comparar las caracteristicas clinicas, de laboratorio y pronostico de neumonia por P. jiroveci en pacientes inmunocomprometidos por infeccion VIH versus no infectados por VIH. Metodos: Analisis retrospectivo de casos confirmados de neumonia por P. jiroveci en adultos con infeccion por VIH y no infectados, entre los anos 2005 y 2007. Resultados: Se incluyeron 28 pacientes infectados por VIH y 45 no infectados, con neumonia por P. jiroveci confirmada. La poblacion no infectada por VIH presentaba mayor edad (65 vs 36,2 anos, p < 0,01), menor duracion de sintomas previos a la consulta (7 [121] vs 14 [2-45] dias, p < 0,01), mayor requerimiento de tecnica invasora (60 vs 21%, p < 0,01) y estudio molecular (93 vs 68%, p < 0,01) para confirmacion diagnostica, mayor requerimiento de camas criticas (58 vs 25%, p < 0,01), y ventilacion mecanica (56 vs 11%, p < 0,01), con mayor mortalidad atribuible (33 vs 0%, p < 0,01). Conclusiones: La neumonia por P. jiroveci en pacientes inmunocomprometidos no infectados por VIH ofrece mas dificultades diagnosticas y presenta mayor gravedad y mortalidad que en pacientes con infeccion por VIH; por esto, es mandatario optimizar los procesos diagnostico y terapeutico en esta poblacion.BACKGROUND Although P. jiroveci pneumonia affects immunocompromised (IC) patients of any etiology, clinical features and prognostic outcomes are different depending if they are patients with HIV infection or other causes of IC. OBJECTIVES To compare clinical and laboratory features as well as outcomes of P. jiroveci pneumonia in HIV versus non-HIV patients. METHODS Retrospective review of clinical records of HIV and non-HIV patients with P. jiroveci pneumonia managed at the Hospital Clínico Universidad Católica in Santiago, Chile, between 2005 and 2007. RESULTS We included 28 HIV and 45 non-HIV patients with confirmed P. jiroveci pneumonia. The non-HIV population was older (65 vs 36,2 years, p < 0,01), had shorter duration of symptoms (7 [1-21] vs 14 [2-45] days, p < 0,01), required more invasive techniques (60 vs 21%, p < 0,01) and RT-PCR to confirm the diagnosis (93 vs 68%, p < 0,01), were more frequently treated at intensive care units (58 vs. 25%, p < 0,01) requiring artificial ventilation (56 vs 11%, p < 0,01), and had a higher attributable mortality (33% vs 0%, p < 0,01). CONCLUSIONS Our study confirmed that P. jiroveci pneumonia in non-HIV IC patients is more severe, more difficult to diagnose and has higher mortality that in HIV patients. Therefore, it is mandatory to optimize diagnostic and therapeutic strategies for this patients group.

Profilaxis antifúngica en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos

Invasive fungal infections are an important cause of morbidity and mortality in SOT and HSCT recipients. The main species involved are Candida spp. and Aspergillus spp, less frequently Cryptococcus spp., causal agents of mucormycosis and Fusarium spp. Usually occur within the first six months post-transplant, but they do it later, especially during episodes of rejection, which maintains the state of immune system involvement. Prophylaxis recommendations are specific to each type of transplant. In liver transplantation use of fluconazole is recommended only in selected cases by high risk factor for invasive fungal infections (A1). If the patient has a high risk of aspergillosis, there are some suggestions for adults population to use amphotericin B-deoxycholate, liposomal amphotericin B or caspofungin (C2) without being validated none of these recommendations in pediatric population. In adult lung transplant patients where the risk of aspergillosis is higher than in other locations, we recommend universal prophylaxis with itraconazole 200 mg/day, nebulised liposomal amphotericin B or voriconazole (C2), no validated recommendations for pediatrics. In HSCT, universal prophylaxis is recommended only in allogeneic and autologous selected cases. The most accepted indication is fluconazole (A1), and posaconazole (A1) or micafungin (A1) in selected cases with high risk of aspergillosis.

H1N1 pandemic influenza impact on hand hygiene and specific precautions compliance among healthcare workers.

After consent, molecular analysis was performed at the National Reference Center for Viral Hepatitis B, C and delta to investigate a possible epidemiological link between the patient and the HCW strains. Genotyping was determined from the nonstructural coding region 5B (NS5B). A phylogenic analysis of nucleotide sequences was performed on a 286 base-pair (bp) fragment within the NS5B region, on a 551 bp fragment within the E1 region and on an 81 bp fragment within the HVR1 region. Sequences were aligned with the Clustal W program and the phylogenic tree analysis was done by the neighbour-joining method, DNADistNeighbor, as implemented in the PHYLIP v3.5 package. The patient and the HCW were both infected with HCV genotype 1a. Phylogenic analysis of the NS5b, E1 and HVR1 regions revealed that the sequences from the patient and the HCW were closely related, with a homology of 50% (Figure 1). We documented a case of HCV transmission to a patient, using epidemiologic and molecular approaches. Genetic and phylogenic analysis of the patient and the home HCW strains suggest a possible HCV transmission during home care. The HCW HCV status was not known before the present investigation, consequently we are unable to confirm patient-to-HCW or HCW-to-patient transmission. Transmissions of bloodborne viruses have been reported in the literature from infected HCW to patients.5,6 Breaches of infection control and a high plasma level of HCV RNA are often associated with a high risk of transmission. In conclusion, this investigation reports a possible case of HCW-to-patient HCV transmission during home care. The infection could be the result of a blood exposure during care of the implantable venous port but the circumstances remain uncertain. Prevention of blood exposure and implementation of standard hygiene precautions, in particular wearing gloves during procedures involving exposure to blood, is the primary way to prevent HCV contamination.

Cambios clínicos y epidemiológicos de candidemias en pacientes adultos desde 2000 a 2013

BACKGROUND Invasive Candida spp. infections have been described more frequently. AIM To characterize the epidemiological data of candidemia in recent years. METHODS A retrospective study of adult patients in a University Hospital in Santiago, Chile, with 1 or more documented episodes of candidemia, from January 2000 to December 2013. RESULTS One hundred and twenty episodes of candidemia were identified in 120 patients, annual incidence of 0.4 cases per 1000 discharges, 53.3% were male patients, 58.3% > 60 years, 77,5% had at least one co-morbidity. Candida albicans was the species most frequently identified 55%, followed by C. glabrata 18.3%, C. tropicalis 11.7% and C. parapsilosis 9.2%. Comparing 2000-2006 vs 2007-2013, increased the frequency of C. parapsilosis among non-albicans and echinocandins prescription. Patients with C. albicans showed higher APACHE-II, more requirement for invasive mechanical ventilation, greater association with CVC, and shorter incubation time compared with non-albicans species. The 30-day mortality was 31.7%. CONCLUSIONS During this 14-years period we observed that C. albicans was the predominant specie and more recently a change among C. non-albicans increasing C. parapsilosis and decreasing C. glabrata 30-days and attributable mortality decreased together with more echinocandins prescription.Background: Invasive Candida spp. infections have been described more frequently. Aim: To characterize the epidemiological data of candidemia in recent years. Methods: A retrospective study of adult patients in a Uni-versity Hospital in Santiago, Chile, with 1 or more documented episodes of candidemia, from January 2000 to December 2013. Results: One hundred and twenty episodes of candidemia were identifiedin 120 patients, annual incidence of 0.4 cases per 1000 discharges, 53.3% were male patients, 58.3% > 60 years, 77,5% had at least one co-morbidity. Candida albicans was the species most frequently identified55%, followed by C. glabrata 18.3%, C. tropicalis 11.7% and C. parapsilosis 9.2%. Comparing 2000-2006 vs 2007-2013, increased the frequency of C. parapsilosis among non-albicans and echinocandins prescription. Patients with C. albicans showed higher APACHE-II, more requirement for invasive mechanical ventilation, greater association with CVC, and shorter incubation time compared with non-albicans species. The 30-day mortality was 31.7%. Conclusions: During this 14-years period we observed that C. albicans was the predominant specie and more recently a change among C. non-albicans increasing C. parapsilosis and decreasing C. glabrata 30-days and attributable mortality decreased together with more echinocandins prescription.