PMID- 18505181
OWN - NLM
STAT- MEDLINE
DCOM- 20080630
LR  - 20201209
IS  - 1359-6535 (Print)
IS  - 1359-6535 (Linking)
VI  - 13
IP  - 2
DP  - 2008
TI  - Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in 
      HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study.
PG  - 297-306
AB  - BACKGROUND: This Phase IIb study explored the antiviral activity and safety of 
      the investigational CCR5 antagonist aplaviroc (APL) in antiretroviral-naive 
      patients harbouring R5-tropic virus. METHODS: One hundred and forty-seven 
      patients were randomized 2:2:1 to one of two APL dosing regimens or efavirenz 
      (EFV). All dosage arms were administered twice daily and in combination with 
      lamivudine/zidovudine (3TC/ZDV; Combivir, COM). Efficacy, safety, and 
      pharmacokinetic parameters were assessed. RESULTS: This study was prematurely 
      terminated due to APL-associated idiosyncratic hepatotoxicity. The primary 
      endpoint of the study was the proportion of patients with plasma HIV-1 RNA <400 
      copies/ml who remained on randomized treatment through week 12. Of the 147 
      patients enrolled, 145 patients received one dose of treatment and were included 
      in the intention-to-treat population. The proportion of patients with HIV-1 RNA 
      <400 copies/ml at week 12 was 53%, 50% and 66% in the APL 600 mg twice daily, APL 
      800 mg twice daily, and EFV arms, respectively. Common clinical adverse events 
      (AEs) were diarrhoea, nausea, fatigue and headache. APL demonstrated non-linear 
      pharmacokinetics with high interpatient variability. In addition to the hepatic 
      findings, there was an apparent dose-response relationship in the incidence of 
      diarrhoea. CONCLUSIONS: Whereas target plasma concentrations of APL were 
      achieved, the antiviral activity of APL as the third agent in a triple drug 
      regimen did not appear to be comparable to EFV in this treatment-naive patient 
      population.
FAU - Currier, Judith
AU  - Currier J
AD  - UCLA Center for Care, Los Angeles, CA, United States. JSCurrier@mednet.ucla.edu
FAU - Lazzarin, Adriano
AU  - Lazzarin A
FAU - Sloan, Louis
AU  - Sloan L
FAU - Clumeck, Nathan
AU  - Clumeck N
FAU - Slims, Jihad
AU  - Slims J
FAU - McCarty, Deb
AU  - McCarty D
FAU - Steel, Helen
AU  - Steel H
FAU - Kleim, Jorg-Peter
AU  - Kleim JP
FAU - Bonny, Tab
AU  - Bonny T
FAU - Millard, Judith
AU  - Millard J
CN  - ASCENT study team
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Benzoates)
RN  - 0 (Diketopiperazines)
RN  - 0 (HIV Fusion Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 0 (Spiro Compounds)
RN  - 2T8Q726O95 (Lamivudine)
RN  - 4B9XT59T7S (Zidovudine)
RN  - 98B425P30V (aplaviroc)
SB  - IM
MH  - Adult
MH  - Aged
MH  - *Anti-HIV Agents/administration & dosage/therapeutic use
MH  - Benzoates/*administration & dosage/*adverse effects/pharmacokinetics/therapeutic 
      use
MH  - Diketopiperazines
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - HIV Fusion Inhibitors/*administration & dosage/*adverse 
      effects/pharmacokinetics/therapeutic use
MH  - HIV Infections/*drug therapy/virology
MH  - Humans
MH  - Lamivudine/administration & dosage/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Piperazines/*administration & dosage/*adverse 
      effects/pharmacokinetics/therapeutic use
MH  - *Reverse Transcriptase Inhibitors/administration & dosage/therapeutic use
MH  - Spiro Compounds/*administration & dosage/*adverse 
      effects/pharmacokinetics/therapeutic use
MH  - Treatment Outcome
MH  - Zidovudine/administration & dosage/therapeutic use
EDAT- 2008/05/29 09:00
MHDA- 2008/07/01 09:00
CRDT- 2008/05/29 09:00
PHST- 2008/05/29 09:00 [pubmed]
PHST- 2008/07/01 09:00 [medline]
PHST- 2008/05/29 09:00 [entrez]
PST - ppublish
SO  - Antivir Ther. 2008;13(2):297-306.