Abstract
BackgroundEarly recognition of antiretroviral therapy (ART) failure in resource limited settings is a challenge given the limited laboratory facilities and trained personnel. This study aimed at describing the incidence, risk factors and the resistance associated mutations (RAMs) of first line treatment failure among HIV-1-infected children attending the Joint Clinical Research Centre (JCRC), Kampala, Uganda.MethodsA retrospective cohort of 701 children who had been initiated on ART between January 2004 and September 2009 at the JCRC was studied. Data of children aged 6 months up to 18 years who had been started on ART for at least 6 months was extracted from the clinic charts. The children who failed the first-line ART were taken as cases and those who did not fail as the controls. Data was analysed using STATA version10.ResultsOf 701 children, 240(34%) failed on first line ART (cases) and 461(66%) did not fail (controls). The overall median time (IQR) to first line ART failure was 26.4 (18.9 – 39.1) months. The factors associated with treatment failure were poor adherence [(OR = 10, 95 CI: 6.4 – 16.7) p < 0.001], exposure to single dose nevirapine (sdNVP) [(OR = 4.2, 95% CI:1.8-9.4), p = 0.005] and a NVP containing regimen [(OR = 2.2,95% CI:1.4-3.6), p < 0.001]. Of 109 genotypic resistance profiles analyzed, the commonest non nucleoside reverse transcriptase inhibitor (NNRTI) resistance associated mutations (RAM) were: K103N (59; 54%)), Y181C (36; 27%)) and G190A (26; 24%)) while the commonest nucleoside reverse transcriptase inhibitor (NRTI) RAM was the M184V (89; 81%). Thymidine analogue- mutations (TAMs) were detected in 20% of patients.ConclusionsOne in three children on first-line ART are likely to develop virological treatment failure after the first 24 months of therapy. Poor adherence to ART, a NVP based first-line regimen, prior exposure to sdNVP were associated with treatment failure.
Highlights
Antiretroviral therapy (ART) has been shown to reduce human immunodeficiency virus (HIV) associated morbidity and mortality by restoring and preserving the immunological function [1,2,3,4,5,6]
Pre-exposure to single dose nevirapine or other antiretroviral drugs as part of a prevention of mother-to- child transmission (PMTCT) regimen could not be entirely ascertained in all the children though, because some children were orphan and brought in by distant relatives and the required information was not readily available
In this study, we have shown that the cumulative incidence of first line ART failure was 34%, with a median time to first line ART failure of 26.4 months of follow up
Summary
Antiretroviral therapy (ART) has been shown to reduce human immunodeficiency virus (HIV) associated morbidity and mortality by restoring and preserving the immunological function [1,2,3,4,5,6]. Treatment failure is suboptimal response or a lack attending one of the largest paediatric ART program in Uganda. Whereas viral load is the ideal tool for monitoring ART response, clinical and immunological monitoring are widely used in resource limited settings like Uganda. There is sufficient evidence suggesting a poor correlation between clinical/immunological and virological ART failure [15,16,17]. In Uganda like many other sub-Saharan countries there is paucity of data regarding paediatric virological treatment failure. Recognition of antiretroviral therapy (ART) failure in resource limited settings is a challenge given the limited laboratory facilities and trained personnel. This study aimed at describing the incidence, risk factors and the resistance associated mutations (RAMs) of first line treatment failure among HIV-1-infected children attending the Joint Clinical Research Centre (JCRC), Kampala, Uganda
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