Posts filed under ‘HIV/SIDA’

Enhanced prophylaxis plus antiretroviral therapy for advanced HIV infection in Africa

N Engl J Med July 20, 2017 V.377 P.233-245.

James Hakim, F.R.C.P., Victor Musiime, Ph.D., Alex J. Szubert, M.Sc., Jane Mallewa, M.D., Abraham Siika, M.Med., Clara Agutu, M.B., Ch.B., M.P.H., Simon Walker, M.Sc., Sarah L. Pett, Ph.D., Mutsa Bwakura-Dangarembizi, M.Med., Abbas Lugemwa, M.D., Symon Kaunda, M.B., Ch.B., Mercy Karoney, M.Sc., Godfrey Musoro, M.Sc., Sheila Kabahenda, M.B., Ch.B., Kusum Nathoo, M.B., Ch.B., Kathryn Maitland, Ph.D., Anna Griffiths, Ph.D., Margaret J. Thomason, Ph.D., Cissy Kityo, M.Sc., Peter Mugyenyi, Ph.D., Andrew J. Prendergast, D.Phil., A. Sarah Walker, Ph.D., and Diana M. Gibb, M.D., for the REALITY Trial Team*

BACKGROUND

In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%.

METHODS

In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim–sulfamethoxazole plus at least 12 weeks of isoniazid–pyridoxine (coformulated with trimethoprim–sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim–sulfamethoxazole alone). The primary end point was 24-week mortality.

RESULTS

A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan–Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had significantly lower rates of tuberculosis (P=0.02), cryptococcal infection (P=0.01), oral or esophageal candidiasis (P=0.02), death of unknown cause (P=0.03), and new hospitalization (P=0.03). However, there was no significant between-group difference in the rate of severe bacterial infection (P=0.32). There were nonsignificantly lower rates of serious adverse events and grade 4 adverse events in the enhanced-prophylaxis group (P=0.08 and P=0.09, respectively). Rates of HIV viral suppression and adherence to ART were similar in the two groups.

CONCLUSIONS

Among HIV-infected patients with advanced immunosuppression, enhanced antimicrobial prophylaxis combined with ART resulted in reduced rates of death at both 24 weeks and 48 weeks without compromising viral suppression or increasing toxic effects. (Funded by the Medical Research Council and others; REALITY Current Controlled Trials number, ISRCTN43622374.)

abstract

http://www.nejm.org/doi/10.1056/NEJMoa1615822

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1615822

 

N Engl J Med  July 20, 2017 V.377 P.283-284

EDITORIAL – The enduring challenge of advanced HIV infection.

Nathan Ford, M.P.H., Ph.D., and Meg Doherty, M.D., Ph.D.

Until recently, progress in the fight against human immunodeficiency virus (HIV) infection was primarily measured in terms of the number of patients who were started on antiretroviral therapy (ART). Major efforts to increase access to ART in the low- and middle-income countries that are most affected by HIV infection began in 2000, and over the following 15 years, an estimated 8 million HIV-related deaths were averted. In countries with a high burden of disease, this decline translated into important increases in life expectancy.1

Notwithstanding these gains, the decrease in HIV-associated deaths appears to have plateaued in recent years. HIV still causes more than 1 million deaths per year worldwide and remains a leading cause of death and complications in sub-Saharan Africa.1 A key explanation for this enduring high mortality is that despite an evolution toward offering treatment earlier in the course of the disease,2 HIV continues to be identified in a substantial number of patients with advanced infection (which is defined by the World Health Organization [WHO] as a CD4+ count of fewer than 200 cells per cubic millimeter). A recent study of trends across 55 countries showed that more than a third (37%) of the patients who initiated ART in 2015 already had advanced HIV infection.3 Such patients are at high risk for death, even after starting ART (which can increase the inflammatory response), and the risk increases with a decreasing CD4+ count.3 A worrisome new trend that has been observed in countries with long-standing HIV treatment programs is an increase in the number of patients who present for care with advanced HIV infection after a period of treatment interruption…..

abstract

http://www.nejm.org/doi/10.1056/NEJMe1707598

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMe1707598

 

August 11, 2017 at 8:27 am

2017-07 Guidelines for the managing advanced HIV disease and rapid initiation of antiretroviral therapy. WHO 56 pags

Overview

The objectives of these guidelines are to provide recommendations outlining a public health approach to managing people presenting with advanced HIV disease, and to provide guidance on the timing of initiation of antiretroviral therapy (ART) for all people living with HIV.

The first set of recommendations addresses the specific needs of people with advanced HIV disease and defines a package of interventions aimed at reducing HIV-associated morbidity and mortality. WHO recommends that a package of screening, prophylaxis, rapid ART initiation and intensified adherence interventions be offered to everyone living with HIV presenting with advanced disease. This is a strong recommendation that applies to all populations and age groups. The guidelines also include an algorithm to support decision making for providing care for people with advanced HIV disease.

The second set of recommendations defines how rapidly ART should be initiated within the context of the “treat all” policy, especially when coinfections are present. WHO strongly recommends that rapid ART initiation should be offered to people living with HIV following confirmed diagnosis and clinical assessment. Rapid initiation of ART is defined as within seven days of HIV diagnosis. WHO further strongly recommends ART initiation on the same day as HIV diagnosis based on the person’s willingness and readiness to start ART immediately, unless there are clinical reasons to delay treatment. Both of these recommendations apply to all populations and age groups. People with advanced HIV disease should be given priority for clinical assessment and treatment initiation.

PDF

http://apps.who.int/iris/bitstream/10665/255884/1/9789241550062-eng.pdf?ua=1

August 7, 2017 at 9:56 am

HIV DRUG RESISTANCE REPORT 2017 – WHO – CDC – The Global Fund 82 pags.

Antimicrobial resistance (AMR) is a growing global public health threat, which urgently requires collective action to ensure effective prevention and treatment of infections. Minimizing the emergence and transmission of HIV drug resistance (HIVDR) is a critical aspect of the broader global response to AMR. Prevention, monitoring and response to HIVDR is key to building and sustaining gains in HIV treatment scale-up, and achieving the global 90-90-90 targets for treatment. These widely adopted targets reflect the global community’s commitment to expanding access to antiretroviral therapy (ART) including: diagnosing 90% of all people with HIV infection; providing treatment to 90% of those diagnosed; and ensuring 90% of people on treatment achieve virological suppression, by 2020. By the end of 2016, 70% of people living with HIV (PLHIV) were diagnosed,77% of those who knew their HIV status received ART, and 82% of those on treatment were virally suppressed…

PDF

http://apps.who.int/iris/bitstream/10665/255896/1/9789241512831-eng.pdf

August 7, 2017 at 8:03 am

Pneumocystis jiroveci pneumonia: comparative study of cases in HIV-infected patients and immunocompromised non-HIV-infected patients.

Rev Chilena Infectol. August 2014 V.31 N.4 P.417-24.

[Article in Spanish]

Cerón I, Rabagliati R, Langhaus J, Silva F, Guzmán AM, Lagos M.

Abstract

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

PDF

http://www.scielo.cl/pdf/rci/v31n4/art07.pdf

July 18, 2017 at 3:44 pm

Pneumocystis pneumonia in hospitalized patients: a detailed examination of symptoms, management, and outcomes in human immunodeficiency virus (HIV)-infected and HIV-uninfected persons.

Transpl Infect Dis. 2012 Oct;14(5):510-8.

McKinnell JA1, Cannella AP, Kunz DF, Hook EW 3rd, Moser SA, Miller LG, Baddley JW, Pappas PG.

Author information

1 Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Abstract

BACKGROUND:

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection for immunocompromised individuals. Robust data and clear guidelines are available for prophylaxis and treatment of human immunodeficiency virus (HIV)-related PCP (HIV-PCP), yet few data and no guidelines are available for non-HIV-related PCP (NH-PCP). We postulated that prevention and inpatient management of HIV-PCP differed from NH-PCP.

METHODS:

We performed a retrospective case review of all pathologically confirmed cases of PCP seen at the University of Alabama Medical Center from 1996 to 2008. Data on clinical presentation, hospital course, and outcome were collected using a standardized data collection instrument. Bivariate analysis compared prophylaxis, adjunctive corticosteroids, and clinical outcomes between patients with HIV-PCP and NH-PCP.

RESULTS:

Our analysis of the cohort included 97 cases of PCP; 65 HIV and 32 non-HIV cases. Non-HIV cases rarely received primary prophylaxis (4% vs. 38%, P = 0.01) and received appropriate antibiotics later in the course of hospitalization (5.2 days vs. 1.1 days, P < 0.005). Among transplant patients, NH-PCP was diagnosed a mean of 1066 days after transplantation and most patients were on low-dose corticosteroids (87%) at the time of disease onset. No significant differences in adjunctive corticosteroid use (69% vs. 77%, P = 0.39) and 90-day mortality (41% vs. 28%, P = 0.20) were detected.

CONCLUSIONS:

Patients who have undergone organ or stem cell transplant remain at risk for PCP for many years after transplantation. In our cohort, patients who developed NH-PCP were rarely given prophylaxis, and initiation of appropriate antibiotics was significantly delayed compared to cases of HIV-PCP. Medical providers should be aware of the ongoing risk for NH-PCP, even late after transplantation, and consider more aggressive approaches to both prophylaxis and earlier empirical therapy for PCP.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889465/pdf/nihms-536426.pdf

July 18, 2017 at 3:43 pm

Aspergilosis. Formas clínicas y tratamiento

Enf Infecciosas & Microbiologia Clínica Abril 2012 V.30 N.4

Jesús Fortún, Yolanda Meije, Gema Fresco, Santiago Moreno.

Servicio de Enfermedades Infecciosas, Hospital Ramón y Cajal, Madrid, España

Resumen

La aspergilosis invasiva junto con la aspergilosis crónica pulmonar y la aspergilosis broncopulmonar alérgica, constituyen las formas clínicas de aspergilosis.

Aunque el número de especies de Aspergillus spp. es muy numeroso, Aspergillus fumigatus-complex es el agente etiológico más frecuente, independientemente de la forma clínica y la afección de base del paciente.

El incremento de los diferentes tratamientos inmunosupresores y el mayor uso de corticoides en pacientes con enfermedad obstructiva crónica han condicionado un mayor protagonismo de la aspergilosis en los últimos años.

El uso de galactomanano y las pruebas de imagen complementan las limitaciones microbiológicas en el diagnóstico de estos pacientes. Voriconazol y anfotericina liposomal constituyen la base del tratamiento en todas las formas de aspergilosis, y posaconazol, itraconazol, caspofungina y otras equinocandinas son alternativas eficaces.

El pronóstico depende de la forma clínica y las características del huésped, pero es sombrío fundamentalmente en las formas invasivas diseminadas.

abstract

http://www.elsevier.es/es-revista-enfermedades-infecciosas-microbiologia-clinica-28-articulo-aspergilosis-formas-clinicas-tratamiento-S0213005X12000316

PDF (hacer CLIC en “DESCARGAR PDF”)

July 17, 2017 at 8:11 am

Características clínicas, diagnósticas y pronósticas de pacientes con neumonía por Pneumocystis jiroveci en individuos infectados por virus de inmunodeficiencia humana e individuos inmunocomprometidos por otra etiología

Rev Chilena Infectol 2014; 31 (4): 417-424

Inés Cerón, Ricardo Rabagliati, Javiera Langhaus, Felipe Silva, Ana M. Guzmán y Marcela Lagos

Pontificia Universidad Católica de Chile, Santiago. Escuela de Medicina Departamento de Enfermedades Infecciosas del Adulto (IC, RR,). Internos de la Escuela de Medicina (JL,FS). Facultad de Medicina Departamento Laboratorios Clínicos (AMG, ML). Lugar de realización del estudio: Hospital Clínico Pontificia Universidad Católica de Chile.

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.

PDF

http://www.scielo.cl/pdf/rci/v31n4/art07.pdf

 

July 16, 2017 at 11:27 am

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