title: Enfuvirtide in HIV-1-infected individuals changing therapy to a nucleoside reverse transcriptase inhibitor sparing regimen: the ALLIANCE Study.
abstract: The role of the fusion inhibitor enfuvirtide in nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens was assessed in an open-label study of fifty-nine highly antiretroviral drug exposed HIV-1-infected individuals. There was a reduction in plasma HIV-1 RNA of 1.43 (95% confidence interval [Cl]: -2.06, -1.22) log10 copies/ml plasma over 96 weeks, and 44% (95% CI: 31, 58) of individuals had a viral load less than 400 copies/ml. A viral load below detection at 96 weeks was predicted by a baseline genotypic sensitivity score greater than 1. There was an average increase of 67 cells/microl (95% Cl: 15, 120) from baseline CD4+ T-cell count to week 96, and the percentage of patients with CD4+ T-cell counts above 100 and 200 cells/microl increased over the trial. Injection site reactions (ISRs) were less common in people with CD4+ T-cell counts >250 cells/microl at any time during follow-up, and were more severe in patients with lower baseline peripheral fat. Adherence over 48 weeks to enfuvirtide injections ranged from 96.3-99.5%. During the 96 week trial there were two discontinuations due to ISRs and two discontinuations following hypersensitivity reactions. Over the 96 weeks of study lean body mass increased by an average 2.7 kg (95% Cl; 1.7, 3.6 kg). Mean peripheral fat increased by 0.2 kg (95% Cl; -0.2, 0.6 kg). Baseline NRTI-associated toxicities resolved in 17% of participants during follow-up. Enfuvirtide is an important component of antiretroviral therapy in highly treatment-experienced individuals where NRTI sparing may be desirable.
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, Australia. dominic_dwyer@wmi.usyd.edu.au
authors.forename: Dominic E
authors.initials: DE
authors.lastname: Dwyer
authors.forename: Cassy
authors.initials: C
authors.lastname: Workman
authors.forename: Gillian
authors.initials: G
authors.lastname: Hales
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: David
authors.initials: D
authors.lastname: Cooper
authors.forename: John
authors.initials: J
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000077560:Enfuvirtide