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Causes of Death in Pediatric Patients Vertically Infected by the Human Immunodeficiency Virus Type 1 in Madrid, Spain, From 1982 to Mid-2009

Palladino, Claudia PhD*; Climent, Francisco J. MD†; José, Ma Isabel De MD‡; Jimenez De Ory, Santiago BSc*; Bellón, Jose María MSc§; Guillén, Sara MD¶; Gurbindo, Ma Dolores MD∥**; González-Tomé, Isabel MD†; Mellado, Ma José MD‡‡; Martínez Pérez, Jorge MD§§; Calvo, Cristina MD¶¶; Ramos, José Tomás MD¶; Muñoz-Fernández, Ma Ángeles PhD, MD***

Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0b013e318211399f
Original Studies
Abstract

Background: Effective therapies have increased life expectancy of human immunodeficiency virus (HIV)-infected pediatric patients. We investigated the underlying causes of death, mortality, and acquired immune deficiency syndrome (AIDS) rates in HIV-infected pediatric patients in Madrid, Spain.

Methods: We studied a multicenter cohort of 478 HIV-infected pediatric patients in Madrid. Mortality and AIDS incidence rates, causes of death, CD4+ T-cell, and HIV RNA were analyzed during calendar periods (CPs): pre-HAART (highly active antiretroviral therapy) (CP1: 1982–1996) and post-HAART era (CP2: 1997–2009).

Results: During 5690 person-years of follow-up 157 (32.8%) deaths occurred. Median age at death increased (CP1: 3.2 years [1.0–6.3] vs. CP2: 7.7 years [3.1–11.4]; P < 0.01). Mortality and AIDS rates decreased 10.6-fold (95% confidence intervals [CI]: 6.9–16.7) and 6.9-fold (95% CI: 5.0–9.6), respectively, between CPs. Nevertheless, mortality was 10.4-fold (95% CI: 5.8–18.8; P < 0.001) higher than in age-similar general population in late-CP2. In all, 169 causes of death were reported. Multiple causes were reported in 16 of 151 (10.6%) patients. In 81.1% (137/169), the causes were AIDS-defining, 11.8% (20/169) HIV-related, and 7.1% (12/169) non-HIV-related. Infections were the leading causes (60.8%, 101/166); from 1999 to 2007 the risk of death from infections was 115.9 times (95% CI: 42.0–265.8; P < 0.001) higher than in the age-similar general population. Comorbidity was reported in 66.9% (101/151) of patients. Median HIV-1 RNA at death decreased (CP1: 5.9 [5.0–6.3]; CP2: 5.3 [4.2–5.8]; P < 0.01).

Conclusions: Despite decline in mortality and AIDS rates, it is important to monitor all causes of death as prolonged survival might allow underlying comorbidity to become more clinically relevant.

Author Information

From the *Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario “Gregorio Marañón,” Madrid, Spain; †Servicio de Pediatría, Hospital Universitario “La Paz,” Madrid, Spain; ‡Servicio de Infecciosas Infantil, Hospital Universitario “La Paz,” Madrid, Spain; §Unidad de Investigación, Fundación para la Investigación Biomédica del Hospital Gregorio Marañón, Madrid, Spain; ¶Servicio de Pediatría, Hospital Universitario de Getafe, Madrid, Spain; ∥Sección Inmuno-Pediatría, Hospital Materno Infantil “Gregorio Marañón,” Madrid, Spain; **Unidad Asociada de Retrovirología Humana, HGUGM-CSIC, Madrid, Spain; ††Servicio de Infecciosas Pediátricas, Hospital Universitario “Doce de Octubre,” Madrid, Spain; ‡‡Servicio de Pediatría, Hospital Universitario “Carlos III,” Madrid, Spain; §§Hospital Infantil Universitario “Niño Jesus,” Madrid, Spain; and ¶¶Servicio de Pediatría, Hospital “Severo Ochoa,” Leganés, Madrid, Spain.

Accepted for publication December 11, 2010.

Supported in part by grants from Red Temática de Investigación Cooperativa Sanitaria ISCIII (RETIC RD06/0006/0035), Fundación para la Investigación y Prevención del SIDA en España, FIPSE (24632/07), Fundación Caja Navarra, Fondo de Investigación Sanitaria (FIS PI061479). The Spanish MICINN through the Juan de la Cierva program (JCI-2009–05650) (to C.P.).

C.P. and F.J.C. contributed equally to the manuscript.

Address for correspondence: Ma Ángeles Muñoz-Fernández, MD, PhD, Laboratorio Inmuno-Biología Molecular, Hospital General Universitario “Gregorio Marañón,” C/Doctor Esquerdo 46, 28007 Madrid, Spain. E-mail: mmunoz.hgugm@salud.madrid.org.

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© 2011 Lippincott Williams & Wilkins, Inc.