2020
DOI: 10.1089/aid.2019.0171
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Perspectives on the Barrier to Resistance for Dolutegravir + Lamivudine, a Two-Drug Antiretroviral Therapy for HIV-1 Infection

Abstract: In HIV-1-infected patients, virological failure can occur as a consequence of the mutations that accumulate in the viral genome that allow replication to continue in the presence of antiretrovirals (ARVs). The development of treatment-emergent resistance to an ARV can limit a patient's options for future therapy, prompting the need for ARV regimens that are resilient to the emergence of resistance. The genetic barrier to resistance refers to the number of mutations in an ARV's therapeutic target that are requi… Show more

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Cited by 35 publications
(17 citation statements)
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“…The efficacy and tolerability of DTG/3TC was comparable to the guideline-recommended three-drug regimen of DTG plus tenofovir disoproxil fumarate and FTC. Thus, DTG/3TC holds much promise to be used as initial therapy for HIV ART-naïve patients, also taking into account the high genetic barrier to resistance of DTG when used in a two-drug regimen with 3TC (Chan and Ly, 2019;Fida et al, 2019;Scott, 2020;Boffito et al, 2020). Other NRTI-associated mutations detected in the present study included the T215 revertant mutations and M41L, which are selected by thymidine analogs, a class of drugs no longer used in current therapeutic regimens (Mazzuti et al, 2020).…”
Section: Discussionmentioning
confidence: 82%
“…The efficacy and tolerability of DTG/3TC was comparable to the guideline-recommended three-drug regimen of DTG plus tenofovir disoproxil fumarate and FTC. Thus, DTG/3TC holds much promise to be used as initial therapy for HIV ART-naïve patients, also taking into account the high genetic barrier to resistance of DTG when used in a two-drug regimen with 3TC (Chan and Ly, 2019;Fida et al, 2019;Scott, 2020;Boffito et al, 2020). Other NRTI-associated mutations detected in the present study included the T215 revertant mutations and M41L, which are selected by thymidine analogs, a class of drugs no longer used in current therapeutic regimens (Mazzuti et al, 2020).…”
Section: Discussionmentioning
confidence: 82%
“…Activation levels were lower among cART-treated patients than VCs, pointing to the undeniable positive effect of cART. In the last decades, drugs with higher genetic barriers and new regimens have been developed [69], bypassing drug resistance issues, improving the survival and quality of life of infected individuals [70][71][72] and decreasing transmission rates [73,74], which supports the expansion of cART coverage and early initiation. In this context, antiretroviral therapy could improve immunological health in viremic controllers, lowering activation levels as observed in cART individuals.…”
Section: Discussionmentioning
confidence: 99%
“…This suggests that DTG monotherapy and certain 2-drug DCRs may be ‘less forgiving’ regarding the risk of resistance development in the setting of VF. This has important implications in real-world settings where a multitude of factors including patient characteristics, disease characteristics and other social and clinical barriers may contribute to higher rates of VF than is observed in randomized clinical trials [ 8 ]. Given the increased use of DCRs globally with several low- and middle-income countries (LMICs) switching to the use of DTG-based therapy as first-and-second line regimens in response to increasing non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance [ 9 – 12 ], real-world studies to evaluate non-traditional combinations of DTG with other antiretroviral (ARV) drugs would be useful to provide further information about the efficacy and barrier to resistance of this second-generation integrase strand transfer inhibitor (INSTI).…”
Section: Introductionmentioning
confidence: 99%