title: Immunologic risk factors for early mortality after starting antiretroviral therapy in HIV-infected Zambian children.
abstract: To explore immunologic risk factors for death within 90 days of highly active antiretroviral therapy (HAART) initiation, CD4(+) and CD8(+) T cell subsets were measured by flow cytometry and characterized by logistic regression in 149 Zambian children between 9 months and 10 years of age enrolled in a prospective, observational study of the impact of HAART on measles immunity. Of 21 children who died during follow-up, 17 (81%) had known dates of death and 16 (76%) died within 90 days of initiating HAART. Young age and low weight-for-age z-scores were associated with increased risks of mortality within 90 days of starting HAART, whereas CD4(+) T cell percentage was not associated with mortality. After adjusting for these factors, each 10% increase in CD8(+) effector T cells increased the odds of overall mortality [OR=1.43 (95% CI: 1.08, 1.90)] and was marginally associated with early mortality [OR=1.29 (95% CI: 0.97, 1.72)]. Conversely, each 10% increase in CD4(+) central memory T cells decreased the odds of overall [OR=0.06 (95% CI: 0.01, 0.59)] and early mortality [OR=0.09 (95% CI: 0.01, 0.97)]. Logistic regression prediction models demonstrated areas under the receiver-operator characteristic curves of ≥85% for early and overall mortality, with bootstrapped sensitivities of 82-85% upon validation, supporting the predictive accuracy of the models. CD4(+) and CD8(+) T cell subsets may be more accurate predictors of early mortality than CD4(+) T cell percentages and could be used to identify children who would benefit from more frequent clinical monitoring after initiating HAART.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Rainwater-Lovett
authors.forename: Hope C
authors.initials: HC
authors.lastname: Nkamba
authors.forename: Mwangelwa
authors.initials: M
authors.lastname: Mubiana-Mbewe
authors.forename: Carolyn Bolton
authors.initials: CB
authors.lastname: Moore
authors.forename: William J
authors.initials: WJ
authors.lastname: Moss
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality*; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D015024:Zambia
chemical_list: D044966:Anti-Retroviral Agents