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The following is a summary of “Dolutegravir/Lamivudine for Maintenance of Virological Suppression in Persons with Historical Suspected or Confirmed Resistance to Lamivudine: Week 48 Results of a Single-Arm, Open-Label, Multicentre, Phase IIA Clinical Trial,” published in the March 2025 issue of Clinical Infectious Diseases by Miguel et al. 

Researchers conducted a retrospective study to assess the efficacy of dolutegravir/lamivudine as a maintenance treatment for individuals with HIV and prior lamivudine resistance.  

They included virologically suppressed individuals with HIV and historical lamivudine resistance (confirmed by genotypic testing or suspected from clinical history), no integrase resistance, and CD4+ >200 cells/mm³. Antiretroviral therapy was switched to dolutegravir/lamivudine if the M184V/I mutation was absent in baseline proviral DNA population sequencing. Baseline samples underwent retrospective proviral DNA next-generation sequencing (NGS). The primary endpoint was the proportion with HIV-1 RNA viral load (VL) ≥50 copies/mL at 48 weeks in the intention-to-treat-exposed (ITT-e) population using the Food and Drug Administration snapshot algorithm.  

The results showed that 121 participants were enrolled, including 114 with prior genotypic detection of M184V/I and a mean virological suppression duration of 9 years. Baseline proviral DNA next-generation sequencing (NGS) identified M184V/I in 24 participants (19.8%, >5% threshold). At 48 weeks, 4 participants (3.3%, 95% CI: 0.9%-8.2%, FDA-Snapshot ITT-e) had a VL ≥50 copies/mL, including 1 confirmed virologic withdrawal, 1 precautionary virologic withdrawal, and 2 who discontinued treatment with a last VL ≥50 copies/mL. None had M184V/I in baseline proviral DNA NGS, and no emergent integrase resistance was detected. A VL <50 copies/mL was observed in 109 participants (90.1%, 95% CI: 83.3%-94.8%), while data were unavailable for 8 participants (6.6%) at 48 weeks.  

Investigators concluded that dolutegravir/lamivudine successfully maintained virological suppression in PWH with CD4+ counts above 200 cells/mm³ and a history of lamivudine resistance, provided proviral DNA lacked lamivudine mutations and that no new resistance emerged. 

Source: academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaf100/8062523