Factors associated with time free of oral candidiasis in children living with HIV / AIDS

In clinical practice, recurrence of thrush is common in children living with HIV/AIDS. The aim of this study was to determine the factors associated with time spent free of oral candidiasis using survival analysis for recurrent events. A retrospective cohort study was carried out with 287 children treated between 1985 and 2009 at a reference center in the city of São Paulo, Brazil. The Prentice, Williams and Peterson model for recurrent events was used for the investigation of factors associated with the time free of oral candidiasis. The following factors were associated with the time patients were free of oral candidiasis: moderate immunodepression (HR = 2.5; p = 0.005), severe immunodepression (HR = 3.5; p < 0.001), anemia (HR = 3.3; p < 0.001), malnutrition (HR = 2.6; p = 0.004), hospitalization (HR = 2.2; p < 0.001), monotherapy (HR = 0.5; p = 0.006), dual therapy (HR = 0.3; p < 0.001) and triple therapy/highly active antiretroviral therapy (HR = 0.1; p < 0.001). The method analyzed in the present study proved useful for the investigation of recurrent events in patients living with HIV/AIDS. Oral Candidiasis; HIV; Acquired Immunodeficiency Syndrome; Child; Survival Analysis Resumo A recorrência da candidíase oral em crianças vivendo com HIV/AIDS é um acontecimento muito comum na prática clínica. O objetivo foi verificar os fatores associados ao tempo livre de candidíase oral, utilizando técnica de análise de sobrevida para eventos recorrentes. Estudo de coorte retrospectivo com 287 crianças, atendidas entre 1985 e 2009, em um serviço de saúde de São Paulo, Brasil. Foi utilizado o modelo marginal para eventos recorrentes de Prentice, Williams e Peterson para investigação dos fatores associados ao tempo livre de candidíase oral. Imunodepressão moderada (HR = 2,5; p = 0,005) ou grave (HR = 3,5; p < 0,001), anemia (HR = 3,3; p < 0,001), desnutrição (HR = 2,6; p = 0,004) e internação (HR = 2,2; p < 0,001), monoterapia (HR = 0,5; p = 0,006), terapia dupla (HR = 0,3; p < 0,001) e terapia tripla/HAART (HR = 0,1; p < 0,001) foram associados ao tempo livre de candidíase oral. A metodologia apresentada neste artigo pode ser bastante útil em pesquisas na área de HIV/AIDS, quando pretende-se estudar eventos com comportamento de recorrência. Candidíase Bucal; HIV; Síndrome de Imunodeficiência Adquirida; Criança; Análise de Sobrevida 2197 ARTIGO ARTICLE http://dx.doi.org/10.1590/0102-311X00069213 Kornstantyner TCRO et al. 2198 Cad. Saúde Pública, Rio de Janeiro, 29(11):2197-2207, nov, 2013 Introduction Persistent oral candidiasis (thrush) is the most frequent fungal condition among children living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) 1. On the systemic level, this population is prone to the development of thrush due to the immunodeficiency caused by the harmful action of HIV on CD4+ T lymphocytes. Locally, an increase in the permeability of the epithelium and change in humoral immunity (IgA) of the oral mucosa stemming from the action of HIV facilitate infection by Candida 2. Other factors commonly found in children living with HIV/AIDS, such as anemia, hospitalization, antiretroviral drugs and broadspectrum antibiotics, have also been implicated in the pathological mechanism of thrush 3,4. Persistent oral candidiasis is considered an important condition in the context of HIV/AIDS, as it affects quality of life and is an indicator of the progression of HIV infection 5,6,7,8,9. Consequently, a large amount of information has been published on the incidence of thrush and associated factors in periods prior to and following the advent of highly active antiretroviral therapy (HAART) using a single episode of thrush per individual as the unit of analysis 10,11,12. However, the recurrence of this condition is a very common event in clinical practice, as children living with HIV/AIDS often experience numerous episodes throughout their lives. Thus, the question arises as to whether the study of factors associated with the occurrence of thrush should consider only a single episode or multiple episodes throughout patient follow-up. Few studies have employed survival analysis techniques developed for recurrent events, such as marginal models, in the investigation of this condition 13,14,15,16,17. Thus, the aim of the present study was to determine factors associated with the time spent free of oral candidiasis in children living with HIV/AIDS using survival analysis for recurrent events.