Aging with HIV: a practical review

The worldwide elderly population is expected to grow by an additional 694 million people by 2025. By that time, there will be approximately two billion elderly people in the world, most of whom (80%) will be living in developing countries. Based on recent estimates, this population will number over 40 million in 2030 in Brazil and a consequent increase in governmental spending for this population can be expected. Since highly active antiretroviral therapy became available in the mid-1990s, the life expectancy of people living with HIV has increased significantly. Approximately 12 million life years were added to the world between 1996 and 2008 as a consequence of wider access to highly active antiretroviral therapy. In Brazil, the incidence of AIDS among the population aged >50 years doubled between 1996 and 2006. The development of antiretroviral therapy has allowed individuals diagnosed at a younger age to live longer, which partially explains the aging tendency associated with the HIV/AIDS epidemic. It is estimated that by 2015, subjects aged >50 years will represent 50% of the people living with HIV undergoing clinical treatment. This scenario presents some challenges, including the fact that the diagnosis of HIV tends to be delayed in older patients compared to younger patients because the symptoms of HIV can be confused with those of other common diseases among the elderly and also because healthcare professionals do not consider this population to be at high risk for HIV infection. In regard to the individuals diagnosed with HIV, a further challenge is presented by the morbidity normally associated with aging. Finally, the elderly also exhibit higher susceptibility to the toxic effects and pharmacological interactions of medications. The present article reviews the literature regarding the profile of HIV infection among individuals aged >50 years focusing on practical features related to the clinical approach and long-term follow-up of this population.

Una década de terapia anti-retroviral: Perfil de pacientes con 10 años de triterapia de alta efectividad / A decade of antiretroviral therapy: a profile of patients with 10 years of highly effective triple therapy

Introduction: Highly effective antiretroviral triple therapy (TAR3) has led to a significant increase in survival of patients (pts) infected with human immunodeficiency virus. In 1999 it was started in the Chilean public health system, including Arriarán Foundation (FA) access to TAR, reaching full coverage since 2003. By October 31, 2009 124 pts had reached 10 years of uninterrupted TAR3 in FA. Objective: To describe and analyze the profile of pts, their therapeutic regimen (s) and clinical outcomes during 10 years of TAR3. Methods: Retrospective descriptive study. We reviewed the records of pts who had reached 10 years of uninterrupted TAR3 in FA. Demographic data, baseline and virological staging at start of TAR3, comorbidities and complications were recorded. Drug regimens used were analyzed, as well as toxicity, virological and immunological outcomes, frequency and reasons for change in therapy. Complications were classified as opportunistic and not opportunistic during this evolution and the latest known clinical and laboratory data were registered. A database program based on Excel was used. Results: 121/124 pts were available for analysis, 76.8% male, male-female ratio was 3.3:1. Baseline median age: 36 years (20-69); CD4 cells 176/ mm³ (8-1,224) with 65.3% < 200; median viral load (STL): 60,078 copies/ml (1,100- 7,900,000); 36.3% were in clinical AIDS stage. Patients received an average of 3.5 therapies regimens during the decade (range, 1 [14 pts, 11.5%] to 7 [3 pts, 2.4%]), with average duration of 42 months each and a median of 36 months. As initial TAR3 regimen 2 backbone nucleoside analogues (ITRN) was the most frequent, with a protease inhibitor (PI) in 51.2% and non-nucleoside RTIs (NNRTIs) in 38.8%. Adverse reactions were the main reason for change of therapy (24.7%), followed by virological failure (24.2%) and treatment simplification (16.6%). At the latest assessment, all with > 10 years of TAR3 median CD4 was 602 cells/mm³, 11 pts (9%) had CD4 < 200/mm³; 85.2% had undetectable VL (< 80 copies/mL); the remaining 14.8% had a median of 1,800 copies/mL. Only 2 pts (1.7%) were in AIDS clinical stage. Current regimens were 2 NRTI plus 1 NNRTI in 61 pts (50.4%), 2 or more NRTI plus 1 PI in 46 (38%). Seventy two pts (60.3%) had chronic comorbidities at latest follow up. Dyslipidemia, hypertension, diabetes mellitus and renal failure were the most frequent conditions; 17 pts (14%) had clinical lipodystrophy secondary to TAR. Conclusion: Achieving a decade of TAR is already a reality and in the short term will be routine. This is rarely achieved with the initial therapeutic regimen. The major obstacles to prolonged maintenance of a single therapeutic regimen have been adverse effects and virological failure, although current drugs with better efficacy and safety profile may allow longer use for each regimen. Despite the difficulty of treating these pts, they can achieve long-term survival with good virologic control, immune recovery and absence of opportunistic complications associated with HIV infection. Nonetheless, the high frequency of non opportunistic chronic comorbidities and antiretroviral therapy side effects after prolonged or life-long use is becoming a major issue.

La introducción de la triterapia anti-retroviral de alta efectividad (TAR3) ha llevado a un significativo aumento en la sobrevida de los pacientes infectados por virus de inmunodeficiencia humana. En 1999 se inició en el sistema público de salud chileno, incluida la Fundación Arriarán (FA) el acceso progresivo a TAR3, que alcanzó cobertura completa desde 2003. En FA al 31 de octubre de 2009 se compatibilizaban 124 pacientes (pts) que habían alcanzado 10 años de TAR3 ininterrumpida. Objetivo: Describir y analizar el perfil de los pts, sus terapias y la evolución clínica durante el período de 10 años de TAR3. Material y Método: estudio descriptivo y retrospectivo. Se revisaron las fichas de los pts que alcanzaron 10 años de TAR3 en FA. Se registraron datos demográficos, clínicos y clasificación por etapas, co-morbilidades y complicaciones al inicio de tratamiento. Se analizaron los esquemas terapéuticos recibidos, toxicidades y desenlaces virológicos e inmunológicos, así como la frecuencia y razones de cambio de terapias, las complicaciones oportunistas y no oportunistas durante esta evolución y el último estado clínico y de laboratorio conocido. Se empleó una base de datos en base al programa Excel. Resultados: se lograron analizar 121/124 pts, 76,8% hombres, relación hombre:mujer 3,3:1. Mediana basal: edad, 36 años (20-69); recuento de linfocitos CD4 de 176 céls/mm³ (8-1.224), con 65,3% < de 200 céls/mm³; carga viral (CV): 60.078 copias/ml (1.100 -7.900.000); 44/121 (36,3%) en etapa SIDA clínica inicial. Los pacientes recibieron un promedio de 3,5 esquemas de terapias durante el decenio (rango, 1 [14 pts, 11,5 %] a 7 [3 pts, 2,4 %]), con duración promedio de 42 meses en cada uno y una mediana de 36. TAR3 inicial con dos análogos nucleosídicos (ITRN) fue lo más frecuente, con un inhibidor de la proteasa (IP) en 51,2% o con ITR no nucleosídico (ITRnN) en 38,8%. Las reacciones adversas fueron el principal motivo de cambio de esquemas (24,7%), seguido de fracaso virológico (24,2%) y simplificación terapéutica (16,6%). En su última evaluación y con > 10 años de TAR3 la mediana de linfocitos CD4 era de 602 céls/mm³; había 11 pts (9 %) con CD4 < 200/ mm³; 85,2% estaba con CV indetectable (< 80 copias/ mL), 14 (14,8%) con detectabilidad viral, y éstos con una mediana de 1.800 copias/mL. Sólo 2 pts (1,7%) estaban en etapa clínica de SIDA. El esquema de TAR3 actual más frecuente era de dos ITRN más un ITRnN, en 61 pts (50,4%) y luego dos ITRN más un IP en 46 (38%). En 72 pts (60,3%) se pesquisaron co-morbilidades crónicas: dislipidemias, hipertensión arterial, diabetes mellitus y/o insuficiencia renal; 17 pts (14%) presentaban lipodistrofia clínica secundaria a TAR3 Conclusión: Alcanzar una década de TAR3 ya está siendo una realidad y a corto plazo será rutinario. Esto rara vez se logra con la primera terapia, aunque esquemas contemporáneos más efectivos y seguros pueden hacerlo posible a futuro. Los principales obstáculos para lograr mantención prolongada de un solo esquema terapéutico son los efectos adversos y el fracaso virológico. A pesar de las dificultades terapéuticas estos pts pueden alcanzar sobrevida a largo plazo con buen control virológico, recuperación inmune y control de las complicaciones oportunistas asociadas a la infección por VIH. Destaca la alta frecuente de co-morbilidades crónicas no oportunistas y secuelas de la terapia anti-retroviral.

Neonatal factors associated with HIV long term non-progressors in a cohort of vertically infected children in Rio de Janeiro, Brazil ("Peixe" Project)

There are only scarce data on HIV progression in vertically infected children in developing countries. The aim of this study is to describe factors from neonatal period associated with long term non-progression (LTNP), in a Brazilian cohort. A cohort study, with data systematically collected from the "Peixe" Cohort (cohort study of children conducted at the main HIV Pediatric Center in Rio de Janeiro, from 1996 to 2005). The study included children who were vertically infected and started follow up at 5 years of age or younger. LTNP, defined as not reaching category C or severe immunosuppression before 5 years of age. Neonatal and demographic factors were studied. Variables with p-value<0.15 were included in a logistic regression model. 213 patients were included, of whom 42 percent (89/213) were classified as LTNP. Variables independently associated with LTNP were: baseline (at study entry) CD4+ cells (per percent) (OR= 1.06, 95 percentCI=1.01-1.12); age of initiating follow-up, per month (OR= 1.03, 95 percentCI=1.01-1.06); ZDV use duriing newborn period (OR= 3.31, 95 percentCI=0.86-12.71); use of antiretroviral (ART) before classification C or severe immunosuppression (OR= 5.89, 95 percentCI=2.03-17.10). Adjusting for age at the beginning of follow-up, antiretroviral that was unsuccessfully used to prevent maternal-to-child transmission (ZDV use in neonatal period) was associated with better prognosis. ARTs initiation before category C or severe immunosuppression was also associated with LTNP.

Impacto de la infección por el virus de la inmunodeficiencia humana Tipo-1 en la población hemofílica / The impact of human immunodeficiency virus infection in haemophilic patients

En los últimos 3 años se han producido notables avances en el tratamiento de la enfermedad HIV/SIDA. En este trabajo se compara la evolución y respuesta al tratamiento con antirretrovirales en 175 pacientes hemofílicos HIV (+) evaluados entre los años 1983 y 1995 con 54 pacientes de las mismas características, pero que recibieron terapias combinadas de alta eficacia, entre los años 1996 y 1999. Se evaluaron los siguientes parámetros: influencia de la edad al momento de la infección con el tiempo de sobrevida libre de enfermedad, incidencia de complicaciones oportunistas, tipo y severidad de la hemofilia en relación con el riesgo de infección por el retrovirus, respuesta al tratamiento antirretroviral, efectos adversos relacionadas con el mismo y modificaciones acaecidas en los niveles de linfocitos T CD4 (+) y en los valores de la carga viral en plasma.