Impact of HIV subtype on response and resistance in antiretroviral-naïve adults comparing treatment with once daily versus twice daily ritonavir boosted fosamprenavir in combination with Abacavir/Lamivudine

  • Lisa L. Ross | Lisa.L.Ross@gsk.com GlaxoSmithKline, Research Triangle Park, NC, United States.
  • Marjorie D. Robinson ViiV Healthcare, Research Triangle Park, NC, United States.
  • Giampiero Carosi Clinica Malattie Infettive e Tropicali, Università degli Studi, Brescia, Italy.
  • Adriano Lazzarin Università “Vita e Salute”, San Raffaele, Milan, Italy.
  • Hans-Juergen Stellbrink 5IInfektionsmedizinisches Centrum Hamburg, Hamburg, Germany.
  • Graeme Moyle St. Stephen's Centre, Chelsea and Westminster Hospital, London, United Kingdom.
  • Naomi Givens GlaxoSmithKline, London, United Kingdom.
  • William G. Nichols GlaxoSmithKline, Research Triangle Park, NC, United States.

Abstract

The impact of HIV-1 subtype on resistance mutation selection and on virologic response to fosamprenavir in combination with once-daily (QD) versus twice-daily (BID) dosing of ritonavir was examined in a prospective, open label, randomized study in antiretroviral-naïve, HIV-1 infected subjects. We studied APV109141 compared QD fosamprenavir/ritonavir (1400mg/100mg) to BID fosamprenavir/ritonavir (700mg/100mg), administered in combination with a QD fixed-dose abacavir/lamivudine (600 mg/300 mg) combination tablet through 48 weeks in ART-naïve subjects. HIV genotypes were obtained from all subjects at screen. Subjects with virologic failure (VF) were also genotyped at baseline and VF. HIV subtypes observed in the ITT (n=214) population were A or AE or AG circulating recombinant forms (CRFs) 19%; B 62%; BF or BG CRFs 2%; C or CPX CRFs 7%; D 2%; F1 7%; G <1%. By TLOVR (ITT-exposed), 86/106 (81%) of subjects on QD study arm and 87/106 (82%) in the BID arm achieved plasma HIV-RNA<400 copies/mL at Week 48. Three subjects met VF criteria, 2 receiving QD fosamprenavir/ritonavir; 1 receiving BID fosamprenavir/ritonavir; (HIV subtype B, F1 A1, respectively). Baseline drug resistance was detected in 2/3 VFs: Subject 1-RT: K103K/N, T215C; major PI: V82A, L90M; and Subject 2-RT: M41L, L74V. Only virus from one subject with VF selected for any treatment-emergent mutation (Subject 1; M184V). Post-VF, Subject 3 (subtypeA1) suppressed HIV-RNA >400 copies/mL through 48 weeks. Subtype appeared to have no preferential impact on virologic response or selection for specific resistance mutations in subjects receiving fosamprenavir/ritonavir. Virologic failure rate was rare (3 subjects; each from different subtypes). At VF, virus from only one subject selected any HIV NRTI mutation (M184V); none selected major protease mutations.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.
Published
2011-12-30
Info
Issue
Section
Original Articles
Keywords:
HIV-1, fosamprenavir, resistance, mutations, subtype
Statistics
  • Abstract views: 1979

  • PDF: 544
How to Cite
Ross, L. L., Robinson, M. D., Carosi, G., Lazzarin, A., Stellbrink, H.-J., Moyle, G., Givens, N., & Nichols, W. G. (2011). Impact of HIV subtype on response and resistance in antiretroviral-naïve adults comparing treatment with once daily versus twice daily ritonavir boosted fosamprenavir in combination with Abacavir/Lamivudine. Drugs and Therapy Studies, 2(1), e1. https://doi.org/10.4081/dts.2012.e1