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Trends in AIDS and Mortality in HIV-Infected Subjects With Hemophilia From 1985 to 2003: The Competing Risks for Death Between AIDS and Liver Disease

del Amo, Julia MD, PhD*; Pérez-Hoyos, Santiago BSc, PhD; Moreno, Alicia BSc; Quintana, Manuel MD; Ruiz, Isabel MD, PhD§; Cisneros, José Miguel MD; Ferreros, Inmaculada BSc; González, Cristina RN, MPH*; de Olalla, Patricia García MD, MPH; Pérez, Rosario MD; Hernández, Ildefonso MD, PhD*Spanish Multicenter Study Group of Seroconverters

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 15th, 2006 - Volume 41 - Issue 5 - p 624-631
doi: 10.1097/01.qai.0000194232.85336.dc
Epidemiology and Social Science

Objective: To study trends in progression to AIDS, all-cause mortality, and cause-specific mortality (AIDS-related, liver disease, and hemorrhagic complications) over calendar periods with different exposure to highly active antiretroviral therapy (HAART) in a cohort of hemophiliacs in Spain, taking into account the competing risks of the causes of death.

Methods: Multicenter cohort of HIV-infected hemophiliacs. HIV seroconversion was estimated using mathematic techniques for interval-censored data from 1979 through 1985. Rates of AIDS and cause-specific death were calculated by Poisson regression, allowing for late entry, for the periods 1985 through 1992, 1993 through 1996, 1997 through 2000 (early HAART), and 2001 through 2003 (late HAART), also allowing for competing risks.

Results: Of 585 subjects, 44% were younger than 15 years of age, 82% had severe hemophilia, 86% had type A hemophilia, and the median seroconversion date was October 1982. Calendar period and age at HIV seroconversion strongly influenced AIDS and death rates. Compared with 1993 through 1996, decreases of 75% (relative risk [RR] = 0.25, 95% confidence interval [CI]: 0.14 to 0.43) and 72% (RR = 0.28, 95% CI: 0.12 to 0.63) in the RR of AIDS were observed in early and late HAART. For all-cause mortality, 72% (RR = 0.28, 95% CI: 0.18 to 0.42) and 83% (RR = 0.17, 95% CI: 0.09 to 0.33) decreases were observed by 1997 through 2000 and 2001 through 2003. For liver-related deaths, increases were observed in the late-HAART period (RR = 2.80, 95% CI: 0.94 to 8.36) compared with 1993 through 1996, but using competing risks, this RR was substantially reduced (RR = 1.70, 95% CI: 0.57 to 5.04).

Discussion: Major reductions in AIDS and death rates were observed from 1997 to 2003 in hemophiliacs. These survival improvements are largely attributable to decreases in AIDS-related deaths and have been accompanied by increases in liver disease death rates, which are overestimated if competing risks are not taken into account.

From the *Department of Public Health, Universidad Miguel Hernández, Alicante, Spain; †Escuela Valenciana de Estudios en Salud, Valencia, Spain; ‡Hospital Universitario La Paz, Madrid, Spain; §Hospital Vall d'Hebron, Barcelona, Spain; ∥Hospital Virgen del Rocío, Sevilla, Spain; and ¶Agència de Salut Pública de Barcelona, Barcelona, Spain.

Received for publication April 14, 2005; accepted October 21, 2005.

Funded through grants from the Fundación para la investigación y la prevención del SIDA en España (FIPSE) integrated by the Spanish Ministry of Health, Abbott Laboratories, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp, and Dohme and Roche (FIPSE 3023/99). Also supported by funds provided by the Spanish Medical Research Fund through grant C03/09 for Red de Centros de Estudios en Salud Pública (RCESP) and from the Fundación La Marató de TV3 (02/1330).

Reprints: Julia del Amo, Public Health Department, Miguel Hernández University, Campus de San Juan Crtra, Alicante-Valencia, Km 87, 03550 San Juan-Alicante, Spain (e-mail:

© 2006 Lippincott Williams & Wilkins, Inc.