Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1

Background: Combination therapy including protease inhibitors has been shown to be effective in treating adults infected with human immunodeficiency virus type 1 (HIV-1), but there are only limited data regarding the treatment of children and adolescents. Methods: A cohort of 1028 HIV-1-infected children and adolescents, from birth through 20 years of age, who were enrolled in research clinics in the United States before 1996 was followed prospectively through 1999. We used proportional-hazards regression models to estimate the effect on mortality of combination therapy including protease inhibitors. Results: Seven percent of the subjects were receiving combination therapy including protease inhibitors in 1996; by 1999, 73 percent were receiving such therapy. In univariate analyses, a higher base-line percentage of lymphocytes that were CD4-positive, a higher weight for age, a higher height for age, black race, Hispanic ethnic background, younger age, and perinatally acquired infection were associated with a longer median time to the initiation of this type of therapy (P<0.001). After adjustment for covariates, the differences among racial and ethnic groups in the time to initiation were not statistically significant. Mortality declined from 5.3 percent in 1996 to 2.1 percent in 1997, 0.9 percent in 1998, and 0.7 percent in 1999 (P for trend <0.001). There were reductions in mortality in all subgroups defined according to age, sex, percentage of CD4+ lymphocytes, educational level of the parent or guardian, and race or ethnic background. In adjusted analyses, the initiation of combination therapy including protease inhibitors was independently associated with reduced mortality (hazard ratio for death, 0.33; 95 percent confidence interval, 0.19 to 0.58; P<0.001). Conclusions: The use of combination therapy including protease inhibitors has markedly reduced mortality among children and adolescents infected with HIV-1. (N Engl J Med 2001;345:1522-8.) Copyright (C) 2001 Massachusetts Medical Society.