Dolutegravir monotherapy in HIV-infected naive patients with an HIV-RNA load <100 000 copies/mL: a medium-term follow-up

The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors

“…Somewhat surprisingly, 3.4% of treatment-naive participants (2 of 58) experienced treatment failure together with the development of resistance mutations in this study, the second case being linked to a M184V substitution in reverse transcriptase [17]. DTG-based dual therapy has proven to maintain HIV-1 suppression in a high proportion (>90%) of patients, even in highly treatment-experienced individuals with some cases of drug resistance development [3,[18][19][20][21]. During the past 2 years, clinical studies of the safety and efficacy of DTG as maintenance monotherapy have been conducted [3,[19][20][21][22].…”

“…DTG-based dual therapy has proven to maintain HIV-1 suppression in a high proportion (>90%) of patients, even in highly treatment-experienced individuals with some cases of drug resistance development [3,[18][19][20][21]. During the past 2 years, clinical studies of the safety and efficacy of DTG as maintenance monotherapy have been conducted [3,[19][20][21][22]. In this clinical setting, individuals have experienced virologic failure with the development of resistance substitutions at various positions in the gene encoding integrase, including Q148H/R, N155H, or G118R [23,24].…”

A systematic review of the genetic mechanisms of dolutegravir resistance

“…There were two small studies of ART-naive persons treated with dolutegravir monotherapy. One was a cohort study of 20 ART-naive persons with baseline plasma HIV-1 RNA levels <100000 copies/mL, of whom 18 maintained virological suppression when receiving dolutegravir monotherapy for a median of 13 months 73 . There was also one dose-finding 10 day dolutegravir monotherapy trial, which recruited 28 participants 74 .…”

Dolutegravir response in antiretroviral therapy naïve and experienced patients with M184V/I: Impact in low-and middle-income settings

“…Better still, its slower dissociation kinetics from HIV integrase and viral DNA complex and high genetic barrier to resistance, further highlight possibility of using DTG as monotherapy for treating HIV infections. Indeed, a number of preclinical studies, patients cohorts and randomised clinical trials, have investigated DTG-monotherapy in both ART naive and virologically suppressed patients (Blanco et al, 2018;Katlama et al, 2016;Lanzafame et al, 2017;Rojas et al, 2016). Despite huge expectations, unexpected high cases of virological failure and resistance have been observed in different studies.…”