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

Abstract

Background: Dolutegravir (DTG) is a cornerstone of global antiretroviral (ARV) therapy (ART) due to its high efficacy and favorable tolerability. However, limited data exist regarding the risk of emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART.

Methods: We performed a PubMed search using the term "Dolutegravir", last updated 18 December 2023, to estimate the prevalence of VF with emergent INSTI DRMs in people living with HIV (PLWH) without previous VF on an INSTI who received DTG-containing ART.

Results: Of 2131 retrieved records, 43 clinical trials, 39 cohorts, and 6 cross-sectional studies provided data across 6 clinical scenarios based on ART history, virological status, and co-administered ARVs: (1) ART-naïve PLWH receiving DTG plus two NRTIs; (2) ART-naïve PLWH receiving DTG plus lamivudine; (3) ART-experienced PLWH with VF on a previous regimen receiving DTG plus two NRTIs; (4) ART-experienced PLWH with virological suppression receiving DTG plus two NRTIs; (5) ART-experienced PLWH with virological suppression receiving DTG and a second ARV; and (6) ART-experienced PLWH with virological suppression receiving DTG monotherapy. The median proportion of PLWH in clinical trials with emergent INSTI DRMs was 1.5% for scenario 3 and 3.4% for scenario 6. In the remaining four trial scenarios, VF prevalence with emergent INSTI DRMs was ≤0.1%. Data from cohort studies minimally influenced prevalence estimates from clinical trials, whereas cross-sectional studies yielded prevalence data lacking denominator details.

Conclusions: In clinical trials, the prevalence of VF with emergent INSTI DRMs in PLWH receiving DTG-containing regimens has been low. Novel approaches are required to assess VF prevalence with emergent INSTI DRMs in PLWH receiving DTG in real-world settings.

Keywords: HIV; epidemiology; systematic review; treatment.

Figure 1

Flow chart summarizing the review process. Of 2131 publications identified in the PubMed search, 345 were read in their entirety following an initial review of titles and abstracts. Exclusions for clinical trials and cross-sectional studies were usually based on a single exclusion criterion. Exclusions for cohort studies were usually based on more than one exclusion criterion. Two publications contained descriptions of two cohorts. Abbreviations: PK—pharmacokinetic study; PLWH—people living with HIV; GRT—genotypic resistance testing; VF—virological failure; 1st-gen INSTI—previous VF on a 1st-generation integrase strand transfer inhibitor (raltegravir or elvitegravir). Heterogeneous/Missing data—indicates that the study described different subsets of individuals with different ART histories, levels of virus suppression, and DTG-containing regimens but that the virological and/or GRT outcomes were not provided for the different subsets.