Early virologic nonresponse to tenofovir, abacavir, and lamivudine in HIV-infected antiretroviral-naive subjects

Joel E. Gallant, Allan E. Rodriguez, Winkler G. Weinberg, Benjamin Young, Daniel S. Berger, Michael L. Lim, Qiming Liao, Lisa Ross, Judy Johnson, Mark S. Shaefer

Research output: Contribution to journalArticle

Abstract

Background. Antiretroviral combinations that reduce the number of pills and dosing frequency have the potential to simplify therapy. We compared 2 regimens dosed as 2 pills once daily. Methods. This was a randomized, open-label, multicenter study of tenofovir disoproxil fumarate versus efavirenz, both administered once daily with the abacavir/lamivudine fixed-dose combination in treatment-naive human immunodeficiency virus type 1 (HIV-1)-infected subjects. After reports of early nonresponse, an unplanned interim analysis was performed. Virologic nonresponse was defined as (1) a 10 copies/mL decrease in HIV-1 RNA level by week 8, (2) an HIV-1 RNA rebound of ≥1.0 log10 copies/mL above the nadir, or (3) for subjects with 2 consecutive HIV-1 RNA measurements 400 copies/mL on 2 consecutive occasions. Results. We randomized 340 subjects. Median baseline HIV-1 RNA level and CD4+ cell count were 4.7 log10 copies/mL and 251 cells/mm3, respectively; 194 subjects with HIV-1 RNA data from ≥8 weeks were included in the interim analysis. Virologic nonresponse occurred in 50 (49%) of 102 subjects in the tenofovir disoproxil fumarate arm, compared with 5 (5%) of 92 of subjects in the efavirenz arm (P <.001). Within 12 weeks, viral genotypes for nonresponders in the tenofovir disoproxil fumarate arm showed M184V or I/M/V mixtures in 40 (98%) of 41 subjects and K65R and M184V or mixtures in 22 (54%) of 41 subjects. The protocol was immediately amended to modify the tenofovir disoproxil fumarate arm. The efavirenz arm continued unchanged; after 48 weeks, 120 (71%) of 169 subjects achieved HIV-1 RNA levels

Original languageEnglish (US)
Pages (from-to)1921-1930
Number of pages10
JournalJournal of Infectious Diseases
Volume192
Issue number11
DOIs
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Fingerprint Dive into the research topics of 'Early virologic nonresponse to tenofovir, abacavir, and lamivudine in HIV-infected antiretroviral-naive subjects'. Together they form a unique fingerprint.

  • Cite this

    Gallant, J. E., Rodriguez, A. E., Weinberg, W. G., Young, B., Berger, D. S., Lim, M. L., Liao, Q., Ross, L., Johnson, J., & Shaefer, M. S. (2005). Early virologic nonresponse to tenofovir, abacavir, and lamivudine in HIV-infected antiretroviral-naive subjects. Journal of Infectious Diseases, 192(11), 1921-1930. https://doi.org/10.1086/498069