Impact of Highly Active Antiretroviral Therapy (HAART) on AIDS and Death in a Cohort of Vertically HIV Type 1-Infected Children: 1980

Abstract

We evaluated the population effectiveness of highly active antiretroviral therapy (HAART) on the risk of AIDS and death in a multicenter cohort of 346 HIV-1 vertically infected children born between 1980 and 2006 in the Comunidad Autónoma de Madrid (CAM), Spain. Risks of AIDS and death in patients with the same duration of HIV infection were compared in different calendar periods [CP1: 1980–1989, CP2: 1990–1993 (reference), CP3: 1994–1996, CP4: 1997–1998, CP5: 1999–2006] through cumulative incidence curves and Cox proportional hazards models, allowing for late entry, that included the calendar period as the time-dependent covariate and adjusting for gender and mother's transmission category. The median follow-up was 11.8 years [interquartile range (IQR), 6.3–15.9]. Median CD4⁺ T cell percentage increased up to 26.5 in CP5 (IQR, 19.5–36.7) while the viral load decreased (median log₁₀ copies/ml in CP5, 3.66; IQR, 3.07–4.22). Multivariate analysis showed significant reduction in the risk of death since 1997 onward [CP4: adjusted hazard ratios (AHR), 0.29; 95% confidence interval (CI), 0.12–0.69; CP5: AHR, 0.06; 95% CI, 0.03–0.15]. Reduction in progression to AIDS reached borderline significance in CP4 (AHR, 0.49; 95% CI, 0.23–1.05) and was more marked in the last period (CP5: AHR, 0.30; 95% CI, 0.16–0.59). The reductions in the incidence of AIDS and death observed since 1996 were largely attributable to HAART.

Get full access to this article

View all access options for this article.

References

Pizzo

, Eddy

, Falloon

et al. Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection. N Engl J Med, 1988; 319:889–896.

Teglas

, Mayaux

, Blanche

. Antiretroviral therapy and mortality among children with perinatal HIV infection. JAMA, 2000; 284:2871–2872.

Fraaij

, Verweel

, van Rossum

et al. Sustained viral suppression and immune recovery in HIV type 1-infected children after 4 years of highly active antiretroviral therapy. Clin Infect Dis, 2005; 40:604–608.

Gibb

, Duong

, Tookey

et al. Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland. BMJ, 2003; 327:1019.

de Martino

, Tovo

, Balducci

et al. Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry. JAMA, 2000; 284:190–197.

Gortmaker

, Hughes

, Cervia

et al. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. N Engl J Med, 2001; 345:1522–1528.

Sanchez

, Ramos Amador

, Fernandez de Miguel

et al. Impact of highly active antiretroviral therapy on the morbidity and mortality in Spanish human immunodeficiency virus-infected children. Pediatr Infect Dis J, 2003; 22:863–867.

McConnell

, Byers

, Frederick

et al. Trends in antiretroviral therapy use and survival rates for a large cohort of HIV-infected children and adolescents in the United States, 1989–2001. J Acquir Immune Defic Syndr, 2005; 38:488–494.

Patel

, Hernan

, Williams

et al. Long-term effectiveness of highly active antiretroviral therapy on the survival of children and adolescents with HIV infection: A 10-year follow-up study. Clin Infect Dis, 2008; 46:507–515.

10.

Centro Nacional de Epidemiología, Instituto de Salud Carlos III: Vigilancia epidemiológica del SIDA en España. Actualización a 31 de Diciembre de 2007. Informe Semestral no. 2, Año, 2007.

11.

Palladino

, Bellon

, Perez-Hoyos

et al. Spatial pattern of HIV-1 mother-to-child-transmission in Madrid (Spain) from 1980 till now: Demographic and socioeconomic factors. AIDS, 2008; 22:2199–2205.

12.

Secretaría del Plan Nacional sobre el SIDA: Encuesta hospitalaria sobre la utilización de recursos y características de los pacientes VIH/SIDA. www.msc.es/sida/epidemiologiaNoviembre 1998. Ministerio de sanidad y Consumo.

13.

Resino

, Resino

, Bellon

et al. Clinical outcomes improve with highly active antiretroviral therapy in vertically HIV type-1-infected children. Clin Infect Dis, 2006; 43:243–252.

14.

European Collaborative Study. Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy. Clin Infect Dis, 2005; 40:458–465.

15.

Centers for Disease Control and Prevention (CDC). Guidelines for use of antiretroviral agents in pediatric HIV infection. MMWR Morb Mortal Wkly Rep, 1998; 47:1–43.

16.

Resino

, Alvaro-Meca

, de Jose

et al. Low immunologic response to highly active antiretroviral therapy in naive vertically human immunodeficiency virus type 1-infected children with severe immunodeficiency. Pediatr Infect Dis J, 2006; 25:365–368.

17.

Centers for Disease Control and Prevention (CDC). Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR CDC Surveill Summ, 1994; 43:1–10. http://www.cdc.gov/mmwr/preview/ mmwrhtml/00032890.htm.

18.

Centers for Disease Control and Prevention (CDC). Revised classification system for HIV-1 infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep, 1992; 41,RR-17:1–19.

19.

Clayton

, Hills

. Statistical Models in Epidemiology Oxford University Press. New York, 1993.

20.

Natural history of vertically acquired human immunodeficiency virus-1 infection. The European Collaborative Study. Pediatrics, 1994; 94:815–819.

21.

Marinda

, Humphrey

, Iliff

et al. Child mortality according to maternal and infant HIV status in Zimbabwe. Pediatr Infect Dis J, 2007; 26:519–526.

22.

Brahmbhatt

, Kigozi

, Wabwire-Mangen

et al. Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda. J Acquir Immune Defic Syndr, 2006; 41:504–508.

23.

Butler

, Husson

, Balis

et al. Dideoxyinosine in children with symptomatic human immunodeficiency virus infection. N Engl J Med, 1991; 324:137–144.

24.

McKinney

Jr , Maha

, Connor

et al. A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group. N Engl J Med, 1991; 324:1018–1025.

25.

Englund

, Baker

, Raskino

et al. Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children. AIDS Clinical Trials Group (ACTG) Study 152 Team. N Engl J Med, 1997; 336:1704–1712.

Impact of Highly Active Antiretroviral Therapy (HAART) on AIDS and Death in a Cohort of Vertically HIV Type 1-Infected Children: 1980–2006

Abstract

Get full access to this article

References