Monotherapy with either dolutegravir or raltegravir fails to durably suppress HIV viraemia in humanized mice.

ABSTRACT:

Objectives

To compare the effectiveness of HIV integrase inhibitor monotherapy between raltegravir and dolutegravir as an approach to simplify therapy.

Methods

We evaluated and compared the efficacy of 20 week monotherapy with dolutegravir or raltegravir in humanized mice (HSC-NSG) infected with HIVBaL. Plasma HIV RNA was measured by quantitative RT-PCR (limit of detection of 150 copies/45 μL of plasma) and drug levels by LC-MS/MS. Escape viruses were genotyped and analysed for replication capacity and drug susceptibility in tissue culture.

Results

Drug-untreated control mice maintained constant viraemia throughout the study. Virus isolates from these mice were susceptible to both raltegravir (EC50 of <8 nM) and dolutegravir (EC50 of <1 nM). Mice treated with raltegra

SUBMITTER: Heredia A 

PROVIDER: S-EPMC5890682 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature