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.

Abstract

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 (<1%), and thymidine analogue mutations (2%) were infrequent. Through week 144, >99% of participants on DTG/3TC and 99% on TBR were virologically suppressed (last on-treatment VL <50 copies/mL) regardless of the presence of major RAMs. Results from the sensitivity analysis by Snapshot were consistent with the last available on-treatment VL. In TANGO, archived, pre-existing major RAMs did not impact virologic outcomes through week 144.

Keywords: 2-drug regimen; HIV-1; antiretroviral therapy; resistance; switch; virologic response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents* / therapeutic use
  • HIV Infections* / drug therapy
  • HIV Seropositivity*
  • HIV-1* / genetics
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Lamivudine / therapeutic use
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Treatment Outcome
  • Viral Load

Substances

  • Lamivudine
  • Reverse Transcriptase Inhibitors
  • dolutegravir
  • Heterocyclic Compounds, 3-Ring
  • Anti-HIV Agents

Associated data

  • ClinicalTrials.gov/NCT03446573

Grants and funding

This research was funded by ViiV Healthcare.