Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV‐1‐infected patients with multidrug‐resistant virus: a multicentre pilot study
Open Access
- 12 August 2008
- journal article
- research article
- Published by Wiley in HIV Medicine
- Vol. 9 (7) , 508-513
- https://doi.org/10.1111/j.1468-1293.2008.00581.x
Abstract
Objectives: To evaluate the safety, immunological outcome and HIV‐1 evolution in the reverse transcriptase (RT) in patients with multidrug resistance receiving zidovudine/lamivudine/abacavir (TZV) plus tenofovir (TDF).Methods: Pilot analysis of highly experienced patients (n=28), with ≥1 thymidine‐associated mutation (TAM) and the M184V mutation.Results: Median of 8.5 treatment regimens, 58% Centers for Disease Control stage C. Baseline (nadir) CD4 count 363 (112) cells/μL. There was a sustained 24‐week drop in viral load (VL) of 0.71 HIV‐1 RNA copies/mL (PP=0.01). Mutations conferring zidovudine hypersusceptibility (Y181C, K65R and L74V) did not improve virological or immunological outcomes. Better CD4 outcomes were seen in patients without M41L (P=0.04) or with baseline VLP=0.01).Conclusions: A bridging regimen with TZV+TDF prevents significant immunological decline and may forestall viral evolution in HIV‐1 RT despite persistent viral replication.Keywords
This publication has 23 references indexed in Scilit:
- Long-Term Immunologic and Virologic Responses in Patients with Highly Resistant HIV Infection Who Are Treated with an Incompletely Suppressive Antiretroviral RegimenClinical Infectious Diseases, 2007
- Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptaseAIDS, 2007
- Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimenAIDS, 2007
- Antiretroviral therapy interruption guided by CD4 cell counts and plasma HIV-1 RNA levels in chronically HIV-1-infected patientsAIDS, 2007
- The K65R Mutation in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Exhibits Bidirectional Phenotypic Antagonism with Thymidine Analog MutationsJournal of Virology, 2006
- Lamivudine monotherapy in HIV-1-infected patients harbouring a lamivudine-resistant virus: a randomized pilot study (E-184V study)AIDS, 2006
- The independent effect of drug resistance on T cell activation in HIV infectionAIDS, 2006
- Broad Nucleoside Reverse‐Transcriptase Inhibitor Cross‐Resistance in Human Immunodeficiency Virus Type 1 Clinical IsolatesThe Journal of Infectious Diseases, 2003
- Diminished RNA Primer Usage Associated with the L74V and M184V Mutations in the Reverse Transcriptase of Human Immunodeficiency Virus Type 1 Provides a Possible Mechanism for Diminished Viral Replication CapacityJournal of Virology, 2003
- Pressure of Zidovudine Accelerates the Reversion of Lamivudine Resistance-Conferring M184V Mutation in the Reverse Transcriptase of Human Immunodeficiency Virus Type 1Antimicrobial Agents and Chemotherapy, 2002