Three‐year efficacy of switching to dolutegravir plus lamivudine: A real‐world study

Abstract

BackgroundDolutegravir (DTG) plus lamivudine (3TC) has proven highly efficacious as a switching strategy in virologically suppressed people with HIV (PWH). As this strategy was introduced relatively recently, real‐world, long‐term durability studies are lacking.MethodsWe performed a retrospective review of treatment‐experienced patients who started DTG + 3TC in a cohort of PWH. HIV‐RNA <50 copies/mL was analysed at 144 weeks in an intention‐to‐treat (ITT) analysis (missing = failure) and a per‐protocol (PP) analysis (patients with missing data or changes for reasons other than virological failure were excluded).ResultsThe study population comprised 358 PWH (19% women). Median age and time with HIV infection were 51.7 and 13.4 years, respectively. The median number of previous antiretroviral combinations was three. Previous virological failure was reported in 27.1% of patients, and the M184V resistance mutation was detected in 17 patients. At 144 weeks, the percentage of individuals with HIV‐RNA <50 copies/mL was 77.4% (277/358) in the ITT analysis and 95.5% (277/290) in the PP analysis. A total of 68 participants were excluded from the PP analysis (data missing, 25, discontinuation due to toxicity, 19; other, 16; death, 8). Two people with virological failure selected resistance‐associated mutations (M184V and M184V + R263K). HIV‐RNA remained undetectable in 17 patients with a previous history of the M184V mutation.ConclusionOur results confirm the real‐world, long‐term efficacy, tolerability and high genetic barrier of DTG + 3TC in treatment‐experienced PWH. Although scarce, mutations causing resistance to nucleosides and integrase can emerge.

Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review

“…Eighteen observational studies described 5930 PLWH with VS for six or more months on a wide variety of previous ART regimens who changed their therapy primarily to DTG/3TC or DTG/rilpivirine ( Supplementary Table S5 ) [ 81 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ]. Sixteen studies were from Western Europe, one was from Turkey, and one was from South Korea.…”

“…VF, which was usually defined as a confirmed plasma HIV-1 RNA level ≥ 50 copies/mL or a single RNA level ≥ 1000 copies/mL, was reported in 203 (2.9%) individuals after a median of 12 months. Of the 41 PLWH undergoing GRT in eleven of the studies, three developed emergent INSTI DRMs including R263K; G118R and R263K; and T66A, G118R, and E138K [ 109 , 111 , 113 ].…”

Treatment Emergent Dolutegravir Resistance Mutations in Individuals Naïve to HIV-1 Integrase Inhibitors: A Rapid Scoping Review

“…Following the review of their titles and abstracts, 232 publications were submitted for full-text review. Following full-text review, 36 publications were found to have reports of INSTI-naïve PLWH who developed one or more INSTI-associated DRMs while receiving DTG [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ], and 21 publications contained in vitro susceptibility results performed using the PhenoSense assay [ 32 , 33 , 35 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , ...…”

A Comprehensive Literature Review of Treatment-Emergent Integrase Resistance with Dolutegravir-Based Regimens in Real-World Settings

“…The proportions of people living with HIV who experienced VF on DTG-based therapy and developed treatment-emergent integrase mutations by study and regimen are shown in Table 1. While the definition of VF varied, many included 1 or 2 consecutive measurements of "detectable" HIV-1 RNA [31,32], or 1 or 2 consecutive measurements of HIV-1 RNA > or ≥50 copies/mL [33][34][35][36][37][38][39][40][41], >200 copies/mL [40,42,43], >400 copies/mL [37,44], ≥500 copies/mL [41], and/or >1000 copies/mL [45,46] as part of study-defined VF criteria. Many did not explicitly define VF criteria [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62].…”

“…Another study of a cohort in Spain reported outcomes for 358 people living with HIV switching to DTG + 3TC before August 2019, which included 17 (4.7%) with a pre-existing M184V resistance mutation. Of the 13 (3.6%) who experienced VF at week 144, none had pre-existing M184V and 1 had treatmentemergent INSTI (R263K) and NRTI (M184V) RAMs; additionally, 1 had treatment-emergent M184V when treatment was changed due to VF at Month 24 [39].…”