PMID- 16964830
OWN - NLM
STAT- MEDLINE
DCOM- 20070806
LR  - 20181201
IS  - 1359-6535 (Print)
IS  - 1359-6535 (Linking)
VI  - 11
IP  - 5
DP  - 2006
TI  - Amdoxovir versus placebo with enfuvirtide plus optimized background therapy for 
      HIV-1-infected subjects failing current therapy (AACTG A5118).
PG  - 619-23
AB  - BACKGROUND: Amdoxovir (2,6-diaminopurine dioxolane; DAPD) is a nucleoside reverse 
      transcriptase inhibitor (NRTI) of human immunodeficiency virus-1 (HIV-1) with 
      activity against wild-type and NRTI-resistant viruses. METHODS: ACTG A5118 
      assessed the antiretroviral activity and safety of DAPD (300 mg orally, twice 
      daily) versus placebo in combination with enfuvirtide (ENF) plus an optimized 
      background (OB) regimen in subjects with failure of two or more antiretroviral 
      (ARV) regimens. The primary endpoints for comparison were time-averaged area 
      under the curve minus baseline (AAUCMB) of plasma HIV-1 RNA concentration at 24 
      weeks and time to first serious (DAIDS toxicity table Grade > or = 3) adverse 
      event (AE). An unplanned interim review recommended closing enrollment because 
      the study was unlikely to demonstrate a difference between arms. The 18 subjects 
      on study, nine in each arm, were unblinded and allowed to continue study 
      treatment through 48 weeks. RESULTS: Intention-to-treat analysis showed the 
      median AAUCMB was -0.9 log10 copies/mL (95% CI = -2.2, -.0.1) in the DAPD arm and 
      -0.9 log10 copies/ml (95% CI = -1.1, -0.1) in the placebo arm (P = 0.69). Median 
      CD4+ T-cell increase was 79 cells/mm3 (95% CI =1, 115) in the DAPD arm and 60 
      (95% CI =1, 101) in the placebo arm (P = 0.45). Time to first serious AE did not 
      differ between arms (P = 0.91). Mild decreases of creatinine clearance were 
      observed with similar frequency between arms; no subject developed lens 
      opacities. CONCLUSIONS: Addition of DAPD to ENF plus OB in advanced subjects with 
      highly resistant virus appeared safe, but did not add statistically significant 
      antiretroviral activity at 24 weeks in this small study.
FAU - Gripshover, Barbara M
AU  - Gripshover BM
AD  - University Hospitals of Cleveland, Case Western Reserve University, Cleveland, 
      OH, USA. gripshover.barb@clevelandactu.org
FAU - Ribaudo, Heather
AU  - Ribaudo H
FAU - Santana, Jorge
AU  - Santana J
FAU - Gerber, John G
AU  - Gerber JG
FAU - Campbell, Thomas B
AU  - Campbell TB
FAU - Hogg, Evelyn
AU  - Hogg E
FAU - Jarocki, Bernadette
AU  - Jarocki B
FAU - Hammer, Scott M
AU  - Hammer SM
FAU - Kuritzkes, Daniel R
AU  - Kuritzkes DR
CN  - A5118 Team
LA  - eng
GR  - AI 38858/AI/NIAID NIH HHS/United States
GR  - AI-054970/AI/NIAID NIH HHS/United States
GR  - AI-25879/AI/NIAID NIH HHS/United States
GR  - AI-27659/AI/NIAID NIH HHS/United States
GR  - AI-32770/AI/NIAID NIH HHS/United States
GR  - AI-34832/AI/NIAID NIH HHS/United States
GR  - AI-46386/AI/NIAID NIH HHS/United States
GR  - RR 016482/RR/NCRR NIH HHS/United States
GR  - RR-00051/RR/NCRR NIH HHS/United States
GR  - U01 AI38855/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Dioxolanes)
RN  - 0 (HIV Envelope Protein gp41)
RN  - 0 (HIV Fusion Inhibitors)
RN  - 0 (Peptide Fragments)
RN  - 0 (Purine Nucleosides)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 19OWO1T3ZE (Enfuvirtide)
RN  - 54I81H0M9C (amdoxovir)
SB  - IM
MH  - Adult
MH  - CD4 Lymphocyte Count
MH  - Dioxolanes/adverse effects/*therapeutic use
MH  - Drug Resistance, Viral
MH  - Drug Therapy, Combination
MH  - Enfuvirtide
MH  - Female
MH  - HIV Envelope Protein gp41/*therapeutic use
MH  - HIV Fusion Inhibitors/*therapeutic use
MH  - HIV Infections/*drug therapy/immunology/virology
MH  - *HIV-1
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Peptide Fragments/*therapeutic use
MH  - Pilot Projects
MH  - Purine Nucleosides/adverse effects/*therapeutic use
MH  - Reverse Transcriptase Inhibitors/adverse effects/*therapeutic use
MH  - Treatment Failure
MH  - Viral Load
EDAT- 2006/09/13 09:00
MHDA- 2007/08/07 09:00
CRDT- 2006/09/13 09:00
PHST- 2006/09/13 09:00 [pubmed]
PHST- 2007/08/07 09:00 [medline]
PHST- 2006/09/13 09:00 [entrez]
PST - ppublish
SO  - Antivir Ther. 2006;11(5):619-23.