Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis

Abstract

Background To investigate the impact of the M184V/I mutation on virologic response to dolutegravir (DTG) + lamivudine (3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with HIV-1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review. Methods Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks. Results Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%-3.81%; interventional: 0.00%) and without (real-world: 0.73%-2.37%). Meta-analysis–estimated proportions (95% CI) with VF were low at Weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [0.00-0.04], 0.03 [0.01-0.06], and 0.04 [0.01-0.07]; interventional: 0.00 [0.00-0.02], 0.00 [0.00-0.01], and 0.00 [0.00-0.03]) and without (real-world: 0.00 [0.00-0.02], 0.02 [0.01-0.04], and 0.02 [0.00-0.05]). One real-world study (n=712) reported treatment-emergent M184V at VF in 1/652 (0.15%) PWH without prior M184V/I. Conclusions Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options.

Dolutegravir/Lamivudine Efficacy and Safety Outcomes in People With HIV-1 With or Without Historical Resistance Results at Screening: 48-Week Pooled Analysis

“…These outcomes are consistent with observations from a systematic literature review and meta-analysis that consisted of 5 real-world evidence–based studies and 5 interventional trials, including TANGO and SALSA, of individuals who were ART experienced and had switched to DTG/3TC while having M184V/I mutations previously detected by historical RNA or archived proviral DNA [ 17 ]. Overall, the systematic literature review showed a low prevalence of M184V/I before the switch to DTG/3TC in the evidence-based studies (11% [264/2428]) and low proportions of virologic failure postswitch among those with historical M184V/I in both the evidence-based studies (week 24, 1.43% [3/210]; week 48, 3.45% [9/261]; week 96, 3.81% [8/210]) and the interventional trials (week 24, 0% [0/42]; week 48, 0% [0/97]; week 96, 0% [0/38]).…”

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

“…Of note, 1 individual with M184V detected in their baseline resistance test achieved virologic suppression by week 6 [71]. A meta-analysis of people living with HIV who switched to DTG + 3TC reported low estimated proportions with VF based on data from real-world cohorts at weeks 24, 48, and 96 regardless of the presence of pre-switch M184V/I mutations (with M184V/I: 0.01, 0.03, and 0.04, respectively; without M184V/I, 0.00, 0.02, and 0.02, respectively), which were consistent with estimated proportions with VF in participants with historical M184V/I from interventional studies (0.00, 0.00, and 0.00, respectively) [72]. Rates of VF were also infrequent 24 weeks after first-line initiation of DTG + 3TC (n = 106) or DTG + TDF/XTC (n = 108) without baseline resistance testing in the randomized phase 4 D2ARLING trial, where no RAMs were observed at VF for the 1 participant taking DTG + TDF/XTC who experienced VF [73].…”