Table 2.

Summary of Resistance Selection in Participants From Real-World Evidence Studies at Virologic Failure According to Study-Defined Virologic Failure Criteria

Study (Cohort)	GRT Availability at Time of VF	INSTI and NRTI RAMs at VF	Key Findings
RWE studies
Hocqueloux 2021 (Dat’AIDS) [13]	4/9 total VFs (0 with known pre-switch M184V/I)	No M184V/I present in participants at VF	Archived M184V/I did not affect the probability of VF after median follow-up of 1.2 y (log-rank test, P = .81), even when stratified by time since last M184V/I detection (log-rank test, P = .94)
Santoro 2022 (LAMRES) [14, 15]	4/32 total VFs (0 with known pre-switch M184V)	No INSTI resistance was reported at VF; n = 1 report of NRTI RAM (M184V) at VFa	Presence vs absence of past M184V did not affect the probability of VF through 3 y on DTG + 3TC (Kaplan-Meier estimates of VF probability at year 3: 13.4% vs 7.0%, respectively) Presence of M184V with ≤3.5 y of virologic suppression before switch had highest risk of VF vs absence of M184V with >3.5 y of virologic suppression but did not reach significance (aHR, 1.9 [95% CI, .5–7.8]; P = .360)
Borghetti 2021 (ODOACRE) [16, 17]	11/12 VFs (2 with known pre-switch M184V/I)b	No participants experiencing VF developed RAMs after failure	Presence of M184V/I alone was not predictive of VF Presence vs absence of M184V/I predicted time to VF (aHR, 3.31 [95% CI, 1.02–10.74]; P = .046)
Galizzi 2020 (NR) [18]	8/17 total VFs (2 with known pre-switch M184V/I)	No development of INSTI resistance was reported	Presence vs absence of historical M184V/I did not affect probability of VF at 1 y (3.1% vs 2.7%; log-rank test, P = .396) Historical M184V/I detection was not associated with VF (aHR, 0.477 [95% CI, .120–1.901]; P = .294) Time between GRT and DTG + 3TC switch was not associated with VF (aHR, 1.023 [95% CI, .969–1.079] per 6 mo longer; P = .416)
Hidalgo-Tenorio 2019 (DOLAMA) [19]	2/5 total VFs (1 with known pre-switch M184V)c	No development of INSTI resistance was reported	Presence of M184V did not affect virologic response to DTG + 3TC
Interventional studies
DOLULAM [20]	0 VFs	No participants met VF criteria	No participants met VF criteria despite potential risk factors: 15/27 (56%) had highest pre-ART VL ≥100 000 copies/mL and 17/27 (63%) had nadir CD4+ cell count <200 cells/μL
TANGO [10]	0 VFs	No participants met VF criteria	All 4 participants with baseline M184V/I maintained virologic suppression at all on-treatment study visits
ART PRO [21]	0 VFs	No participants met VF criteria	6/12 participants who experienced transient viral rebound had historical 3TC resistance; all resuppressed with no change in treatment
SALSA [11]	1/1 VF (0 with known pre-switch M184V)d	NR	5/5 (100%) participants with M184V at baseline maintained VL <40 copies/mL; of these, 4/5 (80%) had VL <40 copies/mL and qualitative target not detected
SOLAR 3D [22]	0 VFs	No RAMs observed through week 48	Similar proportions of participants with vs without historical M184V/I, respectively, had VL <20 copies/mL and target not detected at weeks 24 (80% vs 78%) and 48 (84% vs 80%)

Abbreviations: 3TC, lamivudine; aHR, adjusted hazard ratio; ART, antiretroviral therapy; CI, confidence interval; DTG, dolutegravir; GRT, genotypic resistance test; INSTI, integrase strand transfer inhibitor; NR, not reported; NRTI, nucleoside reverse transcriptase inhibitor; RAM, resistance-associated mutation; VF, virologic failure; VL, viral load.

^aIndividual was virologically suppressed for 1 month before switch, had previous VF due to low adherence, and had VF on the regimen switched to after the VF under DTG + 3TC.

^bAssumption: presence of M184V/I was listed for 2 of 12 participants with VF; whether these indicate pre-switch or time of VF results was not explicit [17].

^cWhether the participant with known pre-switch M184V is 1 of the 2 participants with GRT available at time of VF was not explicit.

^dParticipant had VL ≥50 copies/mL and did not meet confirmed virologic withdrawal criteria.