Mortality in patients with HIV-1 and tuberculosis co-infection in Rio de Janeiro, Brazil - associated factors and causes of death.

BACKGROUND: Tuberculosis is the most frequent opportunistic infection and the leading cause of death among persons living with HIV in several low and middle-income countries. Mortality rates during tuberculosis treatment and death causes among HIV-1/TB co-infected patients may differ based on the immunosuppression severity, timing of diagnosis and prompt initiation of tuberculosis and antiretroviral therapy. METHODS: This was a retrospective observational study conducted in the clinical cohort of patients with HIV-1/Aids of the National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro, Brazil. All HIV-1 infected patients who started combination antiretroviral therapy up to 30 days before or within 180 days after the start of tuberculosis treatment from 2000 to 2010 were eligible. Causes of death were categorized according to the "Coding Causes of Death in HIV" (CoDe) protocol. The Cox model was used to estimate the hazard ratio (HR) of selected mortality variables. RESULTS: A total of 310 patients were included. Sixty-four patients died during the study period. Mortality rate following tuberculosis treatment initiation was 44 per 100 person-years within the first 30 days, 28.1 per 100 person-years within 31 and 90 days, 6 per 100 person-years within 91 and 365 days and 1.6 per 100 person-years after 365 days. Death probability within one year from tuberculosis treatment initiation was approximately 13%. In the adjusted analysis the associated factors with mortality were: CD4 ≤ 50 cells/mm3 (HR: 3.10; 95% CI: 1.720 to 5.580; p = 0.00); mechanical ventilation (HR: 2.81; 95% CI: 1.170 to 6.760; p = 0.02); and disseminated tuberculosis (HR: 3.70; 95% CI: 1.290 to 10.590, p = 0.01). Invasive bacterial disease was the main immediate cause of death (46.9%). CONCLUSION: Our results evidence the high morbidity and mortality among patients co-infected with HIV-1 and tuberculosis in Rio de Janeiro, Brazil. During the first year following tuberculosis diagnosis, mortality was the highest within the first 3 months, being invasive bacterial infection the major cause of death. In order to successfully intervene in this scenario, it is utterly necessary to address the social determinants of health contributing to the inequitable health care access faced by this population.

Survival of AIDS patients using two case definitions, Rio de Janeiro, Brazil, 1986-2003.

BACKGROUND: Recent studies have shown substantial increases in the survival of AIDS patients in developed countries and in Brazil as a result of antiretroviral therapy (ART) and prophylaxis for opportunistic infections. This study compares survival rates using the Brazilian Ministry of Health 2004 and Centers for Disease Control and Prevention (CDC) 1993 case definitions in a large HIV/AIDS referral centre in Rio de Janeiro. METHODS: Survival after AIDS diagnosis was assessed in a clinic-based cohort of 1415 individuals using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: There were 393 (88%) deaths from AIDS-related causes and 52 (12%) from unrelated or unknown causes. A total of 205 patients (14%) were lost to follow-up and 765 patients (55%) remained alive until the end of the study. Three-quarters of patients (75%) were still alive 22 months [95% confidence interval (CI) 19-26] after the AIDS diagnosis according to the CDC case definition and 31 months (95% CI 26-36) according to the Ministry of Health case definition. Independent predictors of survival included AIDS defined by CD4 cell count and any use of highly active antiretroviral therapy, with either case definition, and initial stage of the case, with the Ministry of Health case definition. CONCLUSION: Survival observed in this reference centre is comparable or longer than other international studies, although the choice of case definition criterion influenced findings. Adoption of the Ministry of Health case definition may enhance the ability to track the use of and outcomes from ART among AIDS patients.

Lues maligna in an HIV-infected patient.

We report such a case of malignant syphilis in a 42-year-old HIV-infected man, co-infected with hepatitis B virus, who presented neurolues and the classical skin lesions of lues maligna. The serum VDRL titer, which was 1:64 at presentation, increased to 1:2,048 three months after successful therapy with penicillin, decreasing 15 months later to 1:8.

Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study.

BACKGROUND: Access to combination antiretroviral therapy (ART) is expanding in Latin America (Mexico, Central America, and South America) and the Caribbean. We assessed the incidence of and factors associated with regimen failure and regimen change of initial ART in this region. METHODS: This observational cohort study included antiretroviral-naive adults starting ART from 2000 to 2014 at sites in seven countries throughout Latin America and the Caribbean. Primary outcomes were time from ART initiation until virological failure, major regimen modification, and a composite endpoint of the first of virological failure or major regimen modification. Cumulative incidence of the primary outcomes was estimated with death considered a competing event. FINDINGS: 14,027 patients starting ART were followed up for a median of 3.9 years (2.0-6.5): 8374 (60%) men, median age 37 years (IQR 30-44), median CD4 count 156 cells per µL (61-253), median plasma HIV RNA 5.0 log10 copies per mL (4.4-5.4), and 3567 (28%) had clinical AIDS. 1719 (12%) patients had virological failure and 1955 (14%) had a major regimen change. Excluding the site in Haiti, which did not regularly measure HIV RNA, cumulative incidence of virological failure was 7.8% (95% CI 7.2-8.5) 1 year after ART initiation, 19.2% (18.2-20.2) at 3 years, and 25.8% (24.6-27.0) at 5 years; cumulative incidence of major regimen change was 5.9% (5.3-6.4) at 1 year, 12.7% (11.9-13.5) at 3 years, and 18.2% (17.2-19.2) at 5 years. Incidence of major regimen change at the site in Haiti was 10.7% (95% CI 9.7-11.6) at 5 years. Virological failure was associated with younger age (adjusted hazard ratio [HR] 2.03, 95% CI 1.68-2.44, for 20 years vs 40 years), infection through injection drug use (vs infection through heterosexual sex; 1.60, 1.02-2.52), and initiation in earlier calendar years (1.28, 1.13-1.46, for 2002 vs 2006), but was not significantly associated with boosted protease inhibitor-based regimens (vs non-nucleoside reverse transcriptase inhibitor; 1.17, 1.00-1.36). INTERPRETATION: Incidence of virological failure in Latin America and the Caribbean was generally lower than that reported in North America or Europe. Our results suggest the need to design strategies to reduce failure and major regimen change in young patients and those with a history of injection drug use. FUNDING: US National Institutes of Health.

Multi-state models for defining degrees of chronicity related to HIV-infected patient therapy adherence.

Few studies on AIDS that evaluate factors associated with treatment failure have considered the slow evolution of the disease and multiple health state transitions following the use of antiretrovirals. In this article we study factors associated with the progression between different stages of the disease, focusing on therapy adherence using a sample of 722 HIV+ patients followed up for 3 years. States were defined using the following classifications of the CD4 cell count: s1 (CD4 ≥ 500); s2 (350 ≤ CD4 < 500); and s3 (CD4 < 350). The transitions between states were modeled using multi-state models. Antiretroviral therapy adherence and disease duration were associated with transitions between immune states during follow-up. Low adherence increased the hazard ratio of a transition between s1 to s2 and intermediate adherence increased the hazard ratio of a transition between s2 to s3. On the other hand, older age and disease duration between two and four years are protective factors for AIDS progression. Multi-state modeling is a powerful approach for studying chronic diseases and estimating factors associated with transitions between each stage of progression, thus enabling the use of more individualized and effective interventions.

Multi-state models for defining degrees of chronicity related to HIV-infected patient therapy adherence / Modelos multiestado para determinação dos graus de cronicidade de acordo com a adesão de paciente infectado pelo HIV / Modelos multi-estado para la determinación de los grados de cronicidad, de acuerdo con la adhesión del paciente infectado por el VIH

Few studies on AIDS that evaluate factors associated with treatment failure have considered the slow evolution of the disease and multiple health state transitions following the use of antiretrovirals. In this article we study factors associated with the progression between different stages of the disease, focusing on therapy adherence using a sample of 722 HIV+ patients followed up for 3 years. States were defined using the following classifications of the CD4 cell count: s1 (CD4 ≥ 500); s2 (350 ≤ CD4 < 500); and s3 (CD4 < 350). The transitions between states were modeled using multi-state models. Antiretroviral therapy adherence and disease duration were associated with transitions between immune states during follow-up. Low adherence increased the hazard ratio of a transition between s1 to s2 and intermediate adherence increased the hazard ratio of a transition between s2 to s3. On the other hand, older age and disease duration between two and four years are protective factors for AIDS progression. Multi-state modeling is a powerful approach for studying chronic diseases and estimating factors associated with transitions between each stage of progression, thus enabling the use of more individualized and effective interventions.

Poucos estudos sobre AIDS que avaliam fatores associados à falha terapêutica consideram sua evolução lenta, com a passagem por múltiplos estados de saúde, consequência do uso de antirretrovirais. Nesse artigo foram estudados fatores associados à progressão entre estados imunes, enfocando adesão, em 722 pacientes HIV+ acompanhados por 3 anos. O desfecho foi a contagem de células CD4 classificada em s1 (CD4 ≥ 500), s2 (350 ≤ CD4 < 500) e s3 (CD4 < 350). As transições entre estados foram modeladas por modelos multiestado. A adesão à terapia antirretroviral e o tempo de doença estão associados diferentemente à mudança do estado imune vivido pelo paciente. Baixa adesão à terapia aumentou o risco de s1→s2 e adesão intermediária aumentou o de s2→s3. Por outro lado, idades elevadas e tempo de doença de 2 a 4 anos se apresentam como fatores de proteção na progressão da AIDS. A modelagem multiestado é uma abordagem poderosa no estudo de doenças crônicas, por estimar os fatores associados a cada etapa da evolução de doenças crônicas, possibilitando a adoção de intervenções mais individualizadas e eficazes.

Existen pocos estudios sobre el SIDA que evalúan factores asociados al fallo terapéutico, consideran su evolución lenta, con el pasaje por múltiples estados de salud, consecuencia del uso de antirretrovirales. En ese artículo se estudiaron factores asociados a la progresión entre estados inmunes, enfocando adhesión, en 722 pacientes VIH+ acompañados durante 3 años. El desenlace fue el cómputo de células CD4, clasificado en s1 (CD4 ≥ 500), s2 (350 ≤ CD4 < 500) y s3 (CD4 < 350). Las transiciones entre estados se modelaron por modelos multi-estado. La adhesión a la terapia antirretroviral y el tiempo de enfermedad están asociados diferentemente al cambio del estado inmune vivido por el paciente. Baja adhesión a la terapia aumentó el riesgo de s1→s2 y una adhesión intermedia aumentó de un s2→s3. Por otro lado, edades elevadas y tiempo de enfermedad de 2 a 4 años se presentan como factores de protección en la progresión del SIDA. El modelo multi-estado es un enfoque poderoso en el estudio de enfermedades crónicas, por estimar los factores asociados a cada etapa de la evolución de enfermedades crónicas, posibilitando la adopción de intervenciones más individualizadas y eficaces.

Eventos mórbidos graves e internações hospitalares em uma coorte clínica de pacientes com HIV/AIDS no Rio de Janeiro – Brasil, 2000 - 2010 / Severe morbid events and hospitalizations in a clinical cohort of patients living with HIV/AIDS in Rio de Janeiro, Brazil, 2000- 2010

Introdução: O uso da terapia antiretroviral altamente ativa (HAART) diminuiu significativamente a mortalidade pelo vírus da imunodeficiência humana (HIV) e determinou uma mudança de morbidade relacionada à aids . [...] Métodos: Esta tese é composta por dois artigos científicos. O primeiro estima as taxas de incidência de eventos mórbidos graves em geral, os relacionados a aids e não - relacionados (não - aids ), bem como a taxa de mortalidade e seus determinantes na coorte de indivíduos infectados pelo HIV do Instituto de Pesquisa Evandro Chagas da Fundação Oswaldo Cruz, no Rio de Janeiro, Brasil. O segundo artigo estima o tempo decorrido desde o primeiro teste HIV+ até a primeira internação e os fatores associados a internação . A população do estudo incluiu pacientes adultos ativamente seguidos de 2000 a 2010. As causas de morbidade grave foram definidas como os diagnósticos clínicos ou laboratoriais na alta hospitalar. Os eventos foram verificados e validados por dois médicos experientes no tratamento do HIV. O tempo decorrido entre o primeiro teste HIV+ e a primeira internação foi model ado pelo estimador de Kaplan-Meier. O modelo de riscos proporcionais de Cox foi utilizado para quantificar associação de fatores com o desfecho hospitalização. Resultados: Entre janeiro de 2000 e dezembro de 2010, 3.537 pacientes foram acompanhados por um total de 16.960 pessoas - ano (PA)...(AU)

Background: The wide-spread use of highly active antiretroviral therapy (HAART) has significantly decreased mortality from human immunodeficiency virus (HIV) infection and has determined a shift from AIDS-related morbidity. [...] Methods: This thesis is composed of two scientific papers. The first estimates overall, AIDS and non-AIDS related rates of severe morbidity as well as rates of mortality and its determinants in the cohort of HIV-infected individuals from EvandroChagas Research Institute of the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. The second scientific paper estimates the time since the first HIV+ test and a hospitalization and the factors associated with hospitalizations. The study population included adult patients actively followed from 2000 to 2010. Severe morbidity was defined as the clinical and laboratorial diagnoses at hospitalization discharge. Eventswere systematically checked and validated by two clinicians highly experienced in the management of HIV infection. Kaplan-Meier estimator was used to model the time from the from HIV+ test to hospitalization and Cox proportional hazards model were used to model the association of factors with the hospitalization event...

Lues maligna in an HIV-infected patient

Descrevemos um caso de sífilis maligna em um paciente de 42 anos com infecção pelo HIV e pelo vírus da hepatite B. O paciente, com lesões cutâneas clássicas de lues maligna e VDRL positivo no soro e no líquor, teve uma resposta excelente ao tratamento com penicilina cristalina. O VDRL sérico, que no diagnóstico era de 1:64, aumentou três meses depois para 1:2.048 e diminuiu para 1:8 após 15 meses.