Introduction

The combination of dolutegravir (DTG) and lamivudine (3TC) has shown high virologic suppression rates and low incidences of virologic failure, discontinuation, and drug resistance in phase 3 randomized controlled trials. However, examining real-world evidence can provide insights into treatment outcomes across larger and more diverse patient populations.

Aim 

• A systematic literature review (SLR) was performed to find recent studies on the use of dolutegravir (DTG) combined with lamivudine (3TC) in real-world clinical settings across various populations and time points.
• A meta-analysis evaluated treatment success, failure, and tolerability using data from publications reporting outcomes at Week 48 and/or 96.

Patient Profile

• Individuals naive to antiretroviral therapy (ART)
• Individuals with current/ historical resistance mutations against DTG & or 3TC 
• individuals with prior ART experience with viremia at switch.

Method

• Systematic Literature Review and Meta-analysis
• Studies were selected to include observational research that reported outcomes related to on-treatment virologic suppression (VS) and low rates of virologic failure (VF) or discontinuation at 48 or 96 weeks
• 249 SLR-identified publications represented 44,436 unique individuals using DTG + 3TC: across 43 publications reporting outcomes of interest in the meta-analysis (naive to ART, n = 2346; prior ART, n = 20,060; unspecified pooled, n = 22,030).
• The proportions of individuals exhibiting each outcome at the specified time points were estimated using both random effects and fixed effects models.

Results 

• In treatment-naive individuals, the combination of DTG and 3TC showed low rates of VF, with estimates of 0.001 at week 48 and 0.001 at week 96 based on pooled study data.
•  At weeks 48 & 96, high estimated proportions of individuals with on-treatment VS were observed, with rates of 0.964 and 0.902 for ART-naive participants, and 0.966 and 0.971 for those with prior ART, respectively. (figure 1&2)

Figure 1: Effectiveness and Tolerability of DTG +3TC in ART naïve patients 

Figure 2 :Effectiveness and Tolerability of DTG +3TC in prior ART- experienced patients

•  In a meta-analysis, the estimated proportions of individuals discontinuing treatment were 0.052 at week 48 (figure 1) and 0.130 at week 96 for ART-naive individuals, while for those with prior ART experience, the rates were 0.067 and 0.084 (figure 2), respectively.
• Among the studies reporting reasons for discontinuation, 2.5% of individuals discontinued due to adverse events or toxicities (excluding treatment-unrelated deaths), and 1.0% discontinued specifically due to drug-related adverse events.

RAMs at VF/Blip Among all SLR-Identified Publications

•  None of the individuals who were naïve to ART exhibited any resistance-associated mutations (RAMs) at the time of VF or blips. 
• Among individuals with prior ART experience, 0.02% had integrase strand transfer inhibitor (INSTI) RAMs reported at virologic failure or blip, including mutations such as S147G, R263K, and a combination of T66A + G118R + E138K occurring months after switching to DTG + 3TC.
• The M184V/I treatment-emergent mutation was found in seven individuals with prior ART experience and four with unspecified baseline ART status. However, no RAMs were detected during virologic blips in the studies that reported on resistance outcomes.

Conclusion 

DTG + 3TC is an effective and well-tolerated treatment for diverse populations, including individuals naïve to ART as well as those with prior ART experience, as observed in real-world clinical settings.

Reference 

Infect Dis Ther. 2025; 14:357–383