Serum HIV-1 p24 antibody, HIV-1 RNA copy number and CD4 lymphocyte percentage are independently associated with risk of mortality in HIV-1-infected children

Objective: The role of HIV-1 antibody in modulating disease progression mus t be assessed in the context of other immune and viral load markers. We eva luated the association between HIV-1 p24 antibody, HIV-1 RNA, immune comple x-dissociated (ICD) p24 antigen, CD4 cell percentage, and mortality in a co hort of 218 HIV-infected children enrolled in a trial of intravenous immuno globulin prophylaxis of bacterial infections. Methods: CD4 cell percentage was measured and sera collected and stored at baseline and every 3 months on study (1988-1991). Stored sera were assayed for HIV-1 p24 antibody, HIV-1 RNA, and ICD p24 antigen. Mortality was recor ded during the trial and updated through 1996 (mean total follow-up, 6.3 ye ars). Results: Eighty-one (37%) children died; probability of mortality for child ren with baseline HIV-1 p24 antibody concentrations of undetectable (< 1), 1-4, 5-124, and greater than or equal to 125 reciprocal titer units (RTU) w as 61, 50, 24, and 10%, respectively. A 3.5-fold increase in the relative r isk (RR) of death [95% confidence interval (CI), 2.2-5.5] was observed amon g children with baseline HIV-1 p24 antibody concentration < 5 RTU compared with greater than or equal to 5 RTU. In multivariate analyses, p24 antibody , HIV-1 RNA, and CD4 cell percentage but not ICD p24 antigen were independe ntly associated with mortality; the RR of death increased by 1.7 (95% CI, 1 .3-2.1) for each log(10) decrement in baseline HIV-1 p24 antibody. Conclusions: HIV-1 p24 antibody, HIV-1 RNA and CD4 cell percentage independ ently predict mortality amongst infected children. Whereas CD4 cell percent age provides an estimate of the general degree of immune suppression, HIV-1 p24 antibody could provide an easily obtained, inexpensive assessment of C D4 cell function and could augment prognostic information provided by CD4 c ell count and viral load for clinical management of infected children. (C) 1999 Lippincott Williams & Wilkins.