Oral lesions as predictors of highly active antiretroviral therapy failure in Brazilian HIV-infected children Ivan Dieb Miziara 1 , Raimar Weber 2 1 ENT Discipline, Sao Paulo University Medical School – Group of Otorhinolaryngology and AIDS, Sao Paulo; 2 Post Graduate Studies Under Course, ENT Discipline, Sao Paulo University Medical School, Sao Paulo, Brazil OBJECTIVES: Evaluate the accuracy of HIV-related oral lesions to predict immune and virologic failure on HIV- infected children in use of highly active antiretroviral therapy (HAART). STUDY DESIGN: Data for this cross-sectional analysis come from a longitudinal study being conducted through the HIV-AIDS Outpatient Unit, ENT Division, Hospital das Clinicas, Sao Paulo University Medical School. The study began in January 1990 and is still ongoing. The cut- off point for analyses purposes was December 2004. Subjects were 471 HIV-infected consecutive children attending the outpatient unit during this period, who enrolled regardless of medical or immunological status. The children have undertaken oral cavity examination, serum CD4 + T-lymphocyte count, and, 271 of them, viral load measurement. Sensitivity, specificity, positive pre- dictive value, negative predictive value and relative risk were calculated. RESULTS: Oral lesions had moderate sensitivity, high specificity and positive predictive value to predict immune failure. It had low sensitivity and positive predictive value, and high specificity to predict virologic failure. DISCUSSION AND CONCLUSIONS: Oral manifes- tations of HIV can be important markers for immune suppression and for virologic failure, in Brazilian children undergoing HAART. J Oral Pathol Med (2008) 37: 99–106 Keywords: AIDS; antiretroviral therapy; child; human immuno- deficiency virus; oral candidosis Introduction The use of new antiretroviral drugs, especially protease inhibitors (PI), has markedly reduced mortality and increased life expectancy of population infected by human immunodeficiency virus (HIV; 1–4). HIV disease progression is monitored by two laboratory markers – serum CD4 + cell count (used to assess immune com- petence) and HIV-RNA levels (used to assess HIV replication or viral burden) (5). Both are also used as markers of immune and virologic failure (or success) of antiretroviral therapy. Among the most frequent manifestations of HIV disease, oral lesions (OL) are often among the first symptom in HIV-infected children (6, 7) and have been associated with immune suppression (8), but little is known about relationship of oral opportunistic infec- tions and viral load (VL; 9, 10), specially in children. Besides, OL have been associated with immunological dysfunction and reduced amounts of serum CD4 + T lymphocytes, mainly oral candidosis (OC) and oral hairy leukoplakia (OHL). Those are clinical predictors of AIDS progression and usually are associated with CD4 + T-lymphocytes count <200 cells/mm 3 and high VL levels in adult patients (11–14). The introduction of PI in the mid-1990s produced important therapeutic effects and dramatic changes in the clinical prospect of HIV infection. The rate of all HIV-related OLs, in adult patients, has declined follow- ing introduction of highly active antiretroviral therapy (HAART; 15), mainly oropharyngeal candidosis and hairy leukoplakia (16–21). We also previously described the same changes in a cohort of Brazilian HIV-infected children (22). Although related data are sparing, it has been suggested that the presence of OL related to HIV infection could also be a clinical predictor of HAART failure (23). HAART was usually defined as the associ- ation of a non-nucleoside reverse transcriptase inhibitor (NNRTI), with a nucleoside reverse transcriptase inhibi- tor (NRTI) and a PI or the association of two NNRTI and PI. Patton in a single institution observational cohort involving 606 patients (159 patients < 12 years, 209 patients = 12 years, 238 patients > 12 years) with HIV/AIDS with CD4 + count data and 277 with plasma VL, examined between 1995 and 1999, concluded that specific common OLs are strongly associated with immune suppression and are modestly associated with Correspondence: Ivan Dieb Miziara, Rua Cristiano Viana, 450-121 Sa˜o Paulo, SP 05411-000, Brazil. Tel: 55-11-30811703, Fax: 55-11- 30696565, E-mail: miz@uol.com.br Accepted for publication June 11, 2007 doi: 10.1111/j.1600-0714.2007.00598.x J Oral Pathol Med (2008) 37: 99–106 ª 2007 The Authors. Journal compilation ª Blackwell Munksgaard Æ All rights reserved www.blackwellmunksgaard.com/jopm