These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Mutations associated with virological response to darunavir/ritonavir in HIV-1-infected protease inhibitor-experienced patients.
    Author: Descamps D, Lambert-Niclot S, Marcelin AG, Peytavin G, Roquebert B, Katlama C, Yeni P, Felices M, Calvez V, Brun-Vézinet F.
    Journal: J Antimicrob Chemother; 2009 Mar; 63(3):585-92. PubMed ID: 19147519.
    Abstract:
    OBJECTIVE: The aim of the study was to identify a pattern of protease gene mutations associated with the virological response to darunavir/ritonavir-based regimens. PATIENTS AND METHODS: We analysed 153 treatment-experienced patients receiving a darunavir/ritonavir salvage regimen as a sole protease inhibitor (PI). Virological response was defined as an HIV-1 RNA load of <200 copies/mL at month 3. The impact of individual protease gene mutations on the virological response to darunavir/ritonavir was examined, and the combination of mutations most strongly associated with the virological response was identified. RESULTS: The baseline median HIV RNA level was 4.7 log(10) copies/mL and the median CD4 cell count was 142 cells/mm(3). At month 3, 55% of patients had a virological response and the median fall in viral load from baseline was 1.7 log(10) copies/mL. All the patients had detectable darunavir concentrations at month 3. Cochran-Armitage procedure identified eight mutations with a negative impact on the virological response, namely K14R, K20I, E34Q, I47V, I54M, K55R, T74P and I84V; and two mutations (E35D and V82A) with a positive impact. In multivariate analyses, our genotypic scores were highly predictive of the virological response at month 3, along with the baseline plasma viral load and enfuvirtide co-prescription to enfuvirtide-naive patients. CONCLUSIONS: Among the eight mutations with a negative impact on the virological response, I47V, I54M, T74P and I84V were previously described as darunavir resistance-associated mutations. Some PI resistance mutations had a positive impact on the virological response. These findings might help to explain the potency of darunavir/ritonavir on PI-resistant HIV.
    [Abstract] [Full Text] [Related] [New Search]