The Children with HIV Early Antiretroviral Therapy (CHER) trial is a prospective randomized study evaluating ART strategies in two centers, the Children's Infectious Diseases Clinical Research Unit (KID-CRU), Tygerberg, Cape Town and the Perinatal HIV Research Unit, Soweto, South Africa. All infants were confirmed HIV-positive by polymerase chain reaction (PCR) test. Immunologic criteria for initiating ART in the deferred-therapy group were a CD4 percentage below 20% or, for children younger than 12 months, a CD4 percentage below 25% or a CD4 count below 1000 cells per mm3, according to WHO guidelines updated in 2006 . ART consisted of lopinavir/ritonavir, zidovudine and lamivudine and commenced at baseline in the early ART group. The primary outcomes of interest were death and disease progression.
After randomization, infants were seen every 4 weeks until week 24, every 8 weeks until week 48 and at 12 weekly intervals thereafter. Infants were staged according to criteria of the Centers for Diseases Control and Prevention with stage C and predefined severe stage B criteria used for the study end point of disease progression . These criteria approximated WHO stage 3 and 4 . Persistent otorrhea (duration not defined) is a WHO stage 2 event.
The majority of infants were co-enrolled in a companion study of the 7-valent conjugated Prevnar®Streptococcus pneumoniae vaccine : 36/38 (95%) in the deferred arm and 65/75 (87%) in the early treatment arm. All infants also received the conjugated Haemophilus influenzae B vaccine according to the national immunization program and trimethophrim-sulfamethoxazole (TMP-SMX) prophylaxis.
The CHER study commenced in July 2005. On June 20th, 2007, the Data Safety Monitoring Board (DSMB) stopped the deferred arm after a median of 40 (interquartile range 24 to 58) weeks on study when initial data showed that early ART initiation reduced HIV-related disease progression and mortality by 75% .
Data for the present report were from KID-CRU only. The charts of all infants with CD4% greater than or equal to 25% enrolled in CHER at KID-CRU from August 2005 through June 20, 2007 were reviewed.
Otorrhea was classified as mild (a single episode lasting less than 1 month) or severe (either a single episode lasting more than 1 month or more than 1 episode over the study period). This classification is a modification of that proposed by Sabella . Although WHO accepts more than two weeks of otorrhea for a diagnosis of CSOM, many otorrhinolaryngologists require a duration longer than 3 months . The Committee for Clinical Trials at Stellenbosch University approved both the CHER study and the present sub-analysis (Reference number: M04/07/033A). The trial was conducted in accordance with the Helsinki declaration. A parent, usually the mother, or legal guardian gave written informed consent for each child's participation.
All statistical analyses, including the calculation of risk ratios and confidence intervals (CI), were performed using STATA version 11.0 (STATA Corporation, College Station, TX). Chi-square and Fisher exact tests were performed for categorical variables and Wilcoxon rank tests were performed for continuous variables. All tests were 2-tailed. Significance level was set at 0.05.