EVALUATION OF SURROGATE MARKERS AND CLINICAL OUTCOMES IN 2-YEAR FOLLOW-UP OF 86 HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PEDIATRIC-PATIENTS

Objectives. To evaluate the prognostic value of surrogate markers (HIV RNA copy number, CD4 counts and CDC clinical and immunologic categori es) in HIV-infected children through a 2-year period. Methods, Eighty- six HIV-infected children followed by the Duke Pediatric HIV Clinic in the fall of 1994 were evaluated for plasma HIV RNA concentration (vir al load), CD4 lymphocyte percentage, age, antiretroviral treatment sta tus and CDC clinical and immunologic categories, Follow-up evaluations were performed for similar to 2 years, and the time to progression to a new CDC category C diagnosis or death was noted. Results, Of 86 chi ldren 22 had progression to new Category C diagnosis or death. Seven c hildren died, 17 had a new Category C diagnosis and 2 had both, Among children who progressed, the median CD4 percentage at entry was 3% (ab solute count, 75 cells/mm(3)), whereas children who had no disease pro gression entered with a median of 29% (868 cells/mm(3)), The overall m edian viral load at study entry was 4.58 log(10) copies/ml (38019 copi es/ml, with a range of 1.7 to 6.78 logs), Children who had no disease progression had a median log copy number of 4.43, whereas 5.18 was the median for children whose disease progressed, Log copy number decline d over time in children <3 years of age, whereas it remained fairly co nsistent for children 3 years or older, Progression rates were determi ned by entry plasma HIV RNA concentration quartiles [quartile boundari es <4.18, 4.58, >5.08 log RNA copy/ml (<15136, 38019 and >120226 copie s/ml, respectively)], Progression rates by quartile were 0 of 21, 4 of 22, 5 of 21 and 13 of 22, Kaplan-Meier survival curves defined by CD4 % less than or greater than 15 and log RNA less than or greater than 5 .0 (100000) revealed that patients with CD4% less than 15 and plasma H IV RNA concentration >5 log(10) copies/ml did least well: 11 of 12 (92 %) had a progression event at a median of 179 days, Patients with a hi gh CD4 percentage and high viral load, or a low CD4 percentage and low viral load did similarly; 5 of 14 (36%) and 4 of 12 (33%) had progres sion events, respectively, Patients with high CD4 percentage and low v iral load did best: only 2 of 48 (4%) had a progression event, Conclus ions. The two most significant prognostic indicators of disease progre ssion were the initial CD4 percentage and the plasma HIV RNA concentra tion, and a combination of CD4 percentage and virus load best predicte d which children had progression events, Progression was less common i n children who had <100000 HIV RNA copies/ml initially (6 of 60 vs, 16 of 26; P < 0.001; relative risk 0.16), Therefore it seems reasonable that in a child for whom complete suppression is not possible, a thres hold of 100000 (5 log(10) copies/ml) can be used to mandate a change i n therapy.