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

Abstract

BACKGROUND : 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. AIM : 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. METHODS: 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. RESULTS : 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. CONCLUSIONS : 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.