Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Apr 29:6:90.
doi: 10.3389/fphar.2015.00090. eCollection 2015.

Will drug resistance against dolutegravir in initial therapy ever occur?

Mark A Wainberg  1 , Ying-Shan Han  1
Affiliations
Review

Will drug resistance against dolutegravir in initial therapy ever occur?

Mark A Wainberg et al. Front Pharmacol. .

Abstract

Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor (INSTI) and INSTIs are the latest class of potent anti-HIV drugs. Compared to the first generation INSTIs, raltegravir, and elvitegravir, DTG shows a limited cross-resistance profile. More interestingly, clinical resistance mutations to DTG in treatment-naive patents have not been observed to this date. This review summarizes recent studies on resistance mutations to DTG and on our understanding of the mechanisms of resistance to DTG as well as future directions for research.

Keywords: HIV; antiretroviral; drug resistance; integrase inhibitors.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Chemical structures of (A) raltegravir (RAL), (B) elvitegravir (EVG), and (C) dolutegravir (DTG) and their binding modes to the prototype foamy virus (PFV) integrase active site (Quashie et al., 2013b).
See this image and copyright information in PMC

References

    1. Abram M. E., Hluhanich R. M., Goodman D. D., Andreatta K. N., Margot N. A., Ye L., et al. (2013). Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness. Antimicrob. Agents Chemother. 57 2654–2663 10.1128/AAC.02568-12 - DOI - PMC - PubMed
    1. Anstett K., Mesplede T., Quashie P., Oliveira M. W. (2014). “Primary mutations that confer resistance to raltegravir and elvitegravir are incompatible with the R263K mutation that is associated with low-level resistance to dolutegravir,” in Proceedings of the 20th International AIDS Conference Melbourne, VIC.
    1. Bar-Magen T., Sloan R. D., Donahue D. A., Kuhl B. D., Zabeida A., Xu H., et al. (2010). Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor. J. Virol. 84 9210–9216 10.1128/JVI.01164-10 - DOI - PMC - PubMed
    1. Bastarache S. M., Mesplede T., Donahue D. A., Sloan R. D., Wainberg M. A. (2014). Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. Viruses 6 3487–3499 10.3390/v6093487 - DOI - PMC - PubMed
    1. Cahn P., Pozniak A. L., Mingrone H., Shuldyakov A., Brites C., Andrade-Villanueva J. F., et al. (2013). Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet 382 700–708 10.1016/S0140-6736(13)61221-0 - DOI - PubMed

LinkOut - more resources