Effect of Combination Therapy Including Protease Inhibitors on Mortality among Children and Adolescents Infected with HIV-1
Steven L. Gortmaker, Ph.D., Michael Hughes, Ph.D., Joseph Cervia, M.D., Michael Brady, M.D., George M. Johnson, M.D., George R. Seage, III, D.Sc., M.P.H., Lin Ye Song, Ph.D., Wayne M. Dankner, M.D., James M. Oleske, M.D., M.P.H., for the Pediatric AIDS Clinical Trials Group Protocol 219 Team
Background Combination therapy including protease inhibitorshas been shown to be effective in treating adults infected withhuman immunodeficiency virus type 1 (HIV-1), but there are onlylimited data regarding the treatment of children and adolescents.
Methods A cohort of 1028 HIV-1infected children and adolescents,from birth through 20 years of age, who were enrolled in researchclinics in the United States before 1996 was followed prospectivelythrough 1999. We used proportional-hazards regression modelsto estimate the effect on mortality of combination therapy includingprotease inhibitors.
Results Seven percent of the subjects were receiving combinationtherapy including protease inhibitors in 1996; by 1999, 73 percentwere receiving such therapy. In univariate analyses, a higherbase-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 acquiredinfection were associated with a longer median time to the initiationof this type of therapy (P<0.001). After adjustment for covariates,the differences among racial and ethnic groups in the time toinitiation were not statistically significant. Mortality declinedfrom 5.3 percent in 1996 to 2.1 percent in 1997, 0.9 percentin 1998, and 0.7 percent in 1999 (P for trend <0.001). Therewere reductions in mortality in all subgroups defined accordingto age, sex, percentage of CD4+ lymphocytes, educational levelof the parent or guardian, and race or ethnic background. Inadjusted analyses, the initiation of combination therapy includingprotease inhibitors was independently associated with reducedmortality (hazard ratio for death, 0.33; 95 percent confidenceinterval, 0.19 to 0.58; P<0.001).
Conclusions The use of combination therapy including proteaseinhibitors has markedly reduced mortality among children andadolescents infected with HIV-1.
Source Information
From the Center for Biostatistics in AIDS Research (S.L.G., M.H., G.R.S., L.Y.S.), the Department of Health and Social Behavior (S.L.G.), the Department of Biostatistics (M.H.), and the Department of Epidemiology (G.R.S.), Harvard School of Public Health, Boston; Long Island Jewish Medical Center, New Hyde Park, N.Y. (J.C.); Columbus Children's Hospital, Columbus, Ohio (M.B.); the Medical University of South Carolina, Charleston (G.M.J.); Parexel International and Duke University Medical Center, Durham, N.C. (W.M.D.); and the Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark (J.M.O.).
Address reprint requests to the Center for Biostatistics in AIDS Research at the Harvard School of Public Health, Boston, MA 02115.
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