ART Barrier to Resistance:
Is it quantity or quality of ARVs that counts?
Dr José Gatell Senior Global Medical Director at ViiV Healthcare
However, in reality, these findings reflect the robustness of DTG-based regimens, specifically triple therapy in the DTG trials listed above. What determines the barrier to resistance of a regimen? Is it the number of drugs? We know that even a drug as potent and robust as DTG is not robust enough to use as monotherapy. Clearly, a 3DR is more robust than monotherapy, but is it the number of drugs or the specific drugs that matter? Might two well-selected drugs also comprise an ART regimen with a high barrier to resistance? It is, after all, reasonable to assume that the overall barrier of a regimen comprising fewer selected agents (2DR), could be as high, or higher, than that of a regimen comprising more agents that have not been chosen for their combined barrier to resistance (3DR).
Clinical data: SWORD-1 and -2
Recently, DTG 2DRs have been evaluated in the large SWORD-1 and -2 and GEMINI-1 and -2 clinical trials.
Click to access SWORD study designs
Click to access GEMINI study designs
2DR, two-drug regimen
3DR, three-drug regimen
ART, antiretroviral treatment
CAR, current antiretroviral regimen
Cmax, minimum plasma concentration
CVW, confirmed virologic withdrawal
DDIs, drug-drug interactions
HBV, hepatitis B virus
IC90, concentration to achieve 90% inhibition
INSTI, integrase strand transfer inhibitor
IQ, inhibitory quotient
NRTI, nucleoside reverse transcriptase inhibitor
NNRTI, non-nucleoside reverse transcriptase inhibitor
PI, protease inhibitor
PLHIV, people living with HIV
QD, once daily
TND, target not detected
VL, viral load
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November 2019 PM-GB-2DR-WCNT-190001