Abstract

BackgroundWith improved access to pediatric antiretroviral therapy (ART) in resource-limited settings, more children could experience first-line ART treatment failure.MethodsWe performed a retrospective cohort analysis using electronic medical records from HIV-infected children who initiated ART at McCord Hospital's Sinikithemba Clinic in KwaZulu-Natal, South Africa, from August 2003 to December 2010. We analyzed all records from children who began second-line ART due to first-line treatment failure. We used logistic regression to compare viral outcomes in Protease Inhibitor (PI)-based versus Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-based second-line ART, controlling for time on first-line ART, sex, and whether HIV genotyping guided the regimen change.ResultsOf the 880 children who initiated ART during this time period, 80 (9.1%) switched to second-line ART due to therapeutic failure of first-line ART after a median of 95 weeks (IQR 65–147 weeks). Eight (10%) of the failures received NNRTI-based second-line ART, all of whom failed a PI-based first-line regimen. Seventy (87.5%) received PI-based second-line ART, all of whom failed a NNRTI-based first-line regimen. Two children (2.5%) received non-standard dual therapy as second-line ART. Six months after switching ART regimens, the viral suppression rate was significantly higher in the PI group (82%) than in the NNRTI group (29%; p = 0.003). Forty-one children (51%) were tested for genotypic resistance prior to switching to second-line ART. There was no significant difference in six month viral suppression (p = 0.38) between children with and without genotype testing. Conclusion: NNRTI-based second-line ART carries a high risk of virologic failure compared to PI-based second-line ART.

Highlights

  • Since 2005, there has been a dramatic increase in antiretroviral therapy (ART) access for HIV-infected children in sub-Saharan Africa [1,2,3]

  • Increasing use of single-dose nevirapine (NVP) in Prevention of Mother to Child Transmission (PMTCT) programs could limit the effectiveness of non-nucleoside reverse transcriptase inhibitors (NNRTI) in younger children [11,12]

  • Risk factors for first-line virologic failure among children in this cohort were previously reported [16]. Of those who switched to second-line ART due to virologic failure, 70 (87.5%) failed NNRTI-based first-line ART, eight (10%) failed Protease Inhibitor (PI)-based first-line ART and two (2.5%) failed non-standard dual therapy

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Summary

Introduction

Since 2005, there has been a dramatic increase in ART access for HIV-infected children in sub-Saharan Africa [1,2,3]. Resistance to first-line ART is an increasing problem [5,6,7,8]. With the limited treatment options available, choosing the correct second-line therapy is critical [4,9,10], yet resistance testing is not available in most resource-limited settings. Increasing use of single-dose nevirapine (NVP) in Prevention of Mother to Child Transmission (PMTCT) programs could limit the effectiveness of non-nucleoside reverse transcriptase inhibitors (NNRTI) in younger children [11,12]. Archived resistance mutations in the NVP-exposed infants could potentially limit both first- and second-line use of NNRTI in resource-limited settings [10,13]. With improved access to pediatric antiretroviral therapy (ART) in resource-limited settings, more children could experience first-line ART treatment failure

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