BACKGROUND: The potential toxicity of long-term antiretroviral therapy (ART) requires ongoing investigation of novel strategies for treatment of HIV-infected patients. Monotherapy with the integrase inhibitor (INSTI) dolutegravir (DTG) may offer a favourable safety profile. Additionally, DTG has a high barrier of resistance, crucial for successful maintenance of virological control. However, published data is sparse. METHODS: Retrospective, single-centre cohort study. We enrolled patients on suppressive ART who were switched to DTG monotherapy in routine clinical practice and fulfilled the following inclusion criteria: HIV RNA level <50 copies/ml for ≥6 months at time of switch (one blip <200 copies/ml with re-suppression accepted), no known INSTI resistance or prior INSTI failure, no replicative HBV infection and no history of AIDS. RESULTS: We identified 31 patients with 24-weeks of follow-up data. Previous ART included a non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an INSTI in 32%, 6% and 61% of patients, respectively. At week 24, HIV RNA remained <50 copies/ml in all but two patients (94%). One patient chose to discontinue DTG monotherapy and another developed confirmed virological failure (HIV RNA 538 copies/ml) with new INSTI mutations (Q148H/G140S). Immune status and renal and metabolic function showed no statistically significant changes, apart from a significant decrease in gamma-glutamyl transferase. CONCLUSIONS: De-escalating to DTG monotherapy in selected patients might be a safe and feasible option. However, in one case evolution of INSTI resistance was observed. Further studies should assess particular risk factors for DTG monotherapy failure. In the meanwhile, caution is warranted.
BACKGROUND: The potential toxicity of long-term antiretroviral therapy (ART) requires ongoing investigation of novel strategies for treatment of HIV-infectedpatients. Monotherapy with the integrase inhibitor (INSTI) dolutegravir (DTG) may offer a favourable safety profile. Additionally, DTG has a high barrier of resistance, crucial for successful maintenance of virological control. However, published data is sparse. METHODS: Retrospective, single-centre cohort study. We enrolled patients on suppressive ART who were switched to DTG monotherapy in routine clinical practice and fulfilled the following inclusion criteria: HIV RNA level <50 copies/ml for ≥6 months at time of switch (one blip <200 copies/ml with re-suppression accepted), no known INSTI resistance or prior INSTI failure, no replicative HBV infection and no history of AIDS. RESULTS: We identified 31 patients with 24-weeks of follow-up data. Previous ART included a non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an INSTI in 32%, 6% and 61% of patients, respectively. At week 24, HIV RNA remained <50 copies/ml in all but two patients (94%). One patient chose to discontinue DTG monotherapy and another developed confirmed virological failure (HIV RNA 538 copies/ml) with new INSTI mutations (Q148H/G140S). Immune status and renal and metabolic function showed no statistically significant changes, apart from a significant decrease in gamma-glutamyl transferase. CONCLUSIONS: De-escalating to DTG monotherapy in selected patients might be a safe and feasible option. However, in one case evolution of INSTI resistance was observed. Further studies should assess particular risk factors for DTG monotherapy failure. In the meanwhile, caution is warranted.
Authors: Alonso Heredia; Said Hassounah; Sandra Medina-Moreno; Juan C Zapata; Nhut M Le; Yingshan Han; James S Foulke; Charles Davis; Joseph Bryant; Robert R Redfield; Mark A Wainberg Journal: J Antimicrob Chemother Date: 2017-09-01 Impact factor: 5.790
Authors: Hanh T Pham; Lydia Labrie; Ingeborg E A Wijting; Said Hassounah; Ka Yee Lok; Inna Portna; Mark E Goring; Yingshan Han; Cynthia Lungu; Marchina E van der Ende; Bluma G Brenner; Charles A Boucher; Bart J A Rijnders; Jeroen J A van Kampen; Thibault Mesplède; Mark A Wainberg Journal: J Infect Dis Date: 2018-07-24 Impact factor: 5.226
Authors: Koen K A Van Rompay; Said Hassounah; Brandon F Keele; Jeffrey D Lifson; Amir Ardeshir; Jennifer Watanabe; Hanh Thi Pham; Elena Chertova; Raymond Sowder; Jan Balzarini; Thibault Mesplède; Mark A Wainberg Journal: J Virol Date: 2019-01-04 Impact factor: 5.103
Authors: Ameya R Kirtane; Omar Abouzid; Daniel Minahan; Taylor Bensel; Alison L Hill; Christian Selinger; Anna Bershteyn; Morgan Craig; Shirley S Mo; Hormoz Mazdiyasni; Cody Cleveland; Jaimie Rogner; Young-Ah Lucy Lee; Lucas Booth; Farhad Javid; Sarah J Wu; Tyler Grant; Andrew M Bellinger; Boris Nikolic; Alison Hayward; Lowell Wood; Philip A Eckhoff; Martin A Nowak; Robert Langer; Giovanni Traverso Journal: Nat Commun Date: 2018-01-09 Impact factor: 14.919
Authors: Soo-Yon Rhee; Philip M Grant; Philip L Tzou; Geoffrey Barrow; P Richard Harrigan; John P A Ioannidis; Robert W Shafer Journal: J Antimicrob Chemother Date: 2019-11-01 Impact factor: 5.790