title: Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens.
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.
authors.affiliation: ViiV Healthcare, Research Triangle Park, NC, USA.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Ross
authors.affiliation: Department of Pediatrics and Child Health, Children's Infectious Diseases Clinical Research Unit, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
authors.affiliation: Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Haseena
authors.initials: H
authors.lastname: Cassim
authors.affiliation: Republic Hospital of Infectious Disease, St. Petersburg, Russian Federation.
authors.forename: Eugeny
authors.initials: E
authors.lastname: Voronin
authors.affiliation: GlaxoSmithKline, Stockley Park, UK.
authors.forename: Naomi
authors.initials: N
authors.lastname: Givens
authors.affiliation: GlaxoSmithKline, Stockley Park, UK.
authors.forename: Jorg
authors.initials: J
authors.lastname: Sievers
authors.affiliation: GlaxoSmithKline, Stockley Park, UK.
authors.forename: Katharine Y
authors.initials: KY
authors.lastname: Cheng
keywords: Children; fosamprenavir; mutation; pediatric; resistance