by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer

July 18, 2023

Featured Literature:

Wang R, Wright J, Parminder S, et. al. Assessing the virologic impact of archived resistance in the dolutegravir/lamivudine 2-drug regimen HIV-1 switch study TANGO through Week 144. Viruses. 2023 Jun 11; 15(6): 1350. doi: 10.3390/v15061350. PMID: 37376649 

TANGO investigators retrospectively performed proviral DNA genotyping on baseline samples to determine whether pre-existing mutations impacted treatment response. Proviral testing was performed on 330 in the DTG/3TC group and 324 in the TAF-based 3+-drug regimen (TBR) group. Overall, 320 (DTG/3TC) and 318 (TBR) participants met criteria for inclusion in the proviral DNA resistance analysis population. Archived NRTI mutations were observed in 42/638 (6.6%): M184V/I was present in 7 and K65N/R in 2 participants. In all cases, they were detected as mutation mixtures with wild-type virus. Major INSTI mutations were observed in 11/638 (1.7%): again, all as mixtures with wild-type virus. Of the 7 people with archived M184V/I, 4 were in the DTG/3TC group and had a longer duration of prior ART use compared with the 3 [with M184V/I] in the TBR group. Through week 144, 319/320 (99.7%) on DTG/3TC and 314/318 (98.7%) on TBR were virologically suppressed. Participants with major NRTI, NNRTI, PI or INSTI mutations identified by proviral sequencing had similar virologic response: 81/81 (100%) on DTG/3TC and 87/88 (98.9%) on TBR, including 4 with archived M184V/I on DTG/3TC and 3 with archived M184V/I, as well as 2 with archived K65N/R, on TBR. No participants in the DTG/3TC group experienced virologic withdrawal through week 144, while 3 in the TBR group (all without archived major mutations) experienced virologic withdrawal with no resistance noted at failure.

Author’s Commentary:

Because people with prior virologic failure or documented major NRTI or INSTI resistance were excluded from TANGO, many providers are cautious to limit its use in treatment experienced populations with those historical characteristics. This analysis further adds that retrospective DNA genotyping did not reveal a high frequency of archived ARV resistance in participants and, among the few cases where archived mutations were observed, virologic suppression was maintained through 3 years. Although there may be scenarios where PBMC DNA testing might be considered (e.g., when ART histories are unknown or incomplete prior to switch), results of this study – despite its limitations of small numbers and retrospective nature – suggests such genotyping adds little predictive value for DTG/3TC.   

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