Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens



Lisa L Ross*, 1, Mark F Cotton 2, Haseena Cassim 3, Eugeny Voronin 4, Naomi Givens 5, Jorg Sievers 5, Katharine Y Cheng 5, For the APV29005 & APV20002 Pediatric Study Groups
1 ViiV Healthcare, Research Triangle Park, NC, USA
2 Department of Pediatrics and Child Health, Children’s Infectious Diseases Clinical Research Unit, Stellenbosch University, Tygerberg, South Africa
3 Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa
4 Republic Hospital of Infectious Disease, St. Petersburg, Russian Federation
5 GlaxoSmithKline, Stockley Park, UK


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© Ross et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the ViiV Healthcare Clinical Sciences Group, 5 Moore Drive, Research Triangle Park, NC 27709, USA; Tel: 919-483-6325; E-mail: lisa.l.ross@viivhealthcare.com


Abstract

Treatment-emergent mutations and drug resistance were analyzed in virus from HIV-infected children meeting virologic failure (VF) criteria over 48 weeks following treatment with unboosted fosamprenavir or fosamprenavir/ritonavir-containing regimens in studies APV20002 and APV29005. Both antiretroviral therapy (ART)-naïve and ART-experienced patients were enrolled. Patients met VF criteria by either failing to suppress HIV-RNA to <400 copies/mL through week 24 or after confirmed viral rebound (≥400 copies/mL) anytime through week 48. Viral isolates were analyzed for treatment-emergent mutations or reduced drug susceptibility. Through week 48, 25/109 (23%) of APV29005 and 9/54 (17%) APV20002 study patients met VF. VF was more common in ART-experienced patients (68% and 78%, respectively). Major or minor treatment-emergent mutations were detected at VF in virus from 3 patients receiving unboosted fosamprenavir-containing regimens and in virus from 10 patients receiving fosamprenavir/ritonavir-containing regimens across the two studies. Major protease inhibitor mutations and the reverse transcriptase mutation M184V were detected at VF in virus from 4 and 5 patients, respectively, across both studies. Reduced drug susceptibility to any drug emerged in virus from 9 patients at VF, although reduced fosamprenavir susceptibility emerged in virus from only 4 patients (2 ART-naïve and 2 ART-experienced). No cross-resistance to the protease inhibitor darunavir was observed.

In conclusion, given the high proportion of ART-experienced children (71%) in these two studies, the overall incidence of children meeting VF criteria through 48 weeks was relatively low (21%) and development of fosamprenavir reduced drug susceptibility at VF was uncommon, further supporting the use of fosamprenavir-containing ART regimens in HIV-infected children.

Keywords: Children, fosamprenavir, mutation, pediatric, resistance.