Assessing the Virologic Impact of Archived Resistance in the Dolutegravir/Lamivudine 2-Drug Regimen HIV-1 Switch Study TANGO through Week 144

• Published in: Viruses 2023-06, Vol.15 (6), p.1350
• Main Authors: Wang, Ruolan, Wright, Jonathan, Saggu, Parminder, Ait-Khaled, Mounir, Moodley, Riya, Parry, Chris M, Lutz, Thomas, Podzamczer, Daniel, Moore, Richard, Górgolas Hernández-Mora, Miguel, Kinder, Clifford, Wynne, Brian, van Wyk, Jean, Underwood, Mark
• Format: Article
• Language: English
• Subjects: 2-drug regimen; Acquired immune deficiency syndrome; AIDS; Anti-HIV Agents - therapeutic use; antiretroviral therapy; Archives & records; Brief Report; Care and treatment; Diagnosis; Drug dosages; Drug resistance; Drug withdrawal; FDA approval; Genotype & phenotype; Genotypes; Heterocyclic Compounds, 3-Ring - therapeutic use; HIV; HIV (Viruses); HIV Infections - drug therapy; HIV Seropositivity; HIV-1; HIV-1 - genetics; Human immunodeficiency virus; Humans; Integrase; Lamivudine; Lamivudine - therapeutic use; Mutation; Non-nucleoside reverse transcriptase inhibitors; Nucleoside reverse transcriptase inhibitors; Plasma; Proteinase inhibitors; resistance; Retrospective Studies; Reverse Transcriptase Inhibitors - therapeutic use; RNA-directed DNA polymerase; Sensitivity analysis; switch; Tenofovir; Thymidine; Treatment Outcome; Viral Load; virologic response
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15061350

The TANGO study (ClinicalTrials.gov, NCT03446573) demonstrated that switching to dolutegravir/lamivudine (DTG/3TC) was non-inferior to continuing tenofovir alafenamide-based regimens (TBR) through week 144. Retrospective baseline proviral DNA genotypes were performed for 734 participants (post-hoc analysis) to assess the impact of archived, pre-existing drug resistance on 144-week virologic outcomes by last on-treatment viral load (VL) and Snapshot. A total of 320 (86%) participants on DTG/3TC and 318 (85%) on TBR had both proviral genotype data and ≥1 on-treatment post-baseline VL results and were defined as the proviral DNA resistance analysis population. Archived International AIDS Society-USA major nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, protease inhibitor, and integrase strand transfer inhibitor resistance-associated mutations (RAMs) were observed in 42 (7%), 90 (14%), 42 (7%), and 11 (2%) participants, respectively, across both groups; 469 (74%) had no major RAMs at baseline. M184V/I (1%), K65N/R (99% of participants on DTG/3TC and 99% on TBR were virologically suppressed (last on-treatment VL