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Pediatr Infect Dis J. 2014 Feb;33(2):e53-9. doi: 10.1097/INF.0b013e31829f2694.

Consequences of prior use of full-dose ritonavir as single protease inhibitor as part of combination antiretroviral regimens on the future therapy choices in HIV-1-infected children.

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From the *Department of Paediatrics, Kalafong Hospital; †Department of Family Medicine; ‡Department of Immunology, University of Pretoria, Pretoria, South Africa; §Department of Pediatrics, Yale University, New Haven, CT; and ¶Department of Paediatrics and Child Health, University of Stellenbosch, Tygerberg, South Africa.



South African HIV-infected infants below age 6 months and children younger than 3 years on concomitant antimycobacterial treatment received full-dose ritonavir single protease inhibitor (RTV-sPI), together with 2 nucleoside reverse transcriptase inhibitors, from 2004 until 2008. Use of RTV-sPI has been described as a risk factor for PI drug resistance, but the extent of this resistance is unknown.


This research assesses clinical and virological outcome of a pediatric RTV-sPI cohort at a large South African antiretroviral therapy (ART) site in a high-burden tuberculosis setting, including resistance mutations in those failing ART.


All children initiated at Kalafong hospital before December 2008, who ever received RTV-sPI-based regimens, were assessed for patient outcome, virological failure and drug resistance. HIV viral loads were done 6-monthly and HIV genotyping since 2009.


There were 178 children who ever received RTV-sPI, with a mean age at ART initiation of 1.4 years. Of the 135 children (76%) with >6 months follow-up, 17 children (13%) never had viral suppression, whereas another 25 (18%) developed virological failure later. Nineteen of 26 children (73%) with genotypic resistance results had major PI mutations.


Treatment failure is not a universal feature in children with prior exposure to RTV-sPI regimens, but the significant proportion (31%) with virological failure is of concern due to high prevalence of major PI- and multiclass mutations. These children currently have no treatment options in the South African public sector, highlighting the urgent need for access to alternative ART regimens to ensure improved outcomes.

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