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

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) (CP11982–1996) and post-HAART era (CP21997–2009). RESULTS:During 5690 person-years of follow-up 157 (32.8%) deaths occurred. Median age at death increased (CP13.2 years [1.0–6.3] vs. CP27.7 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% CI5.0–9.6), respectively, between CPs. Nevertheless, mortality was 10.4-fold (95% CI5.8–18.8; 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% CI42.0–265.8; 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 (CP15.9 [5.0–6.3]; CP25.3 [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.