Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study. Antiviral therapy [Antivir Ther] Journal article | | Title | Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study. | | Author(s) | Currier J, Lazzarin A, Sloan L, Clumeck N, Slims J, McCarty D, Steel H, Kleim JP, Bonny T, Millard J, ASCENT study team | | Institution | UCLA Center for Care, Los Angeles, CA, United States. JSCurrier@mednet.ucla.edu | | Source | Antivir Ther 2008; 13(2):297-306. | | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 18505181 |
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