Two-Drug HIV Therapy Effective Without Resistance Testing

TOPLINE:

Dolutegravir plus lamivudine demonstrates noninferiority to the standard-of-care three-drug regimen in treatment-naive patients with HIV without preliminary drug resistance testing.

METHODOLOGY:

• Researchers conducted a randomized, noninferiority, phase 4 trial to evaluate the efficacy and safety of dolutegravir plus lamivudine in untreated patients with HIV with no preliminary drug resistance testing.
• Overall, 223 participants (median age, 31 years; 77% men) were enrolled, of whom 106 received the two-drug regimen of dolutegravir plus lamivudine and 108 received the three-drug regimen of dolutegravir plus tenofovir disoproxil fumarate with either emtricitabine or lamivudine.
• Drug resistance testing was performed at the start of the treatment and was kept double-blinded until study completion, mimicking a scenario in which information on drug resistance testing is unavailable at treatment initiation.
• The primary endpoint was the percentage of participants with < 50 copies/mL of HIV-1 ribonucleic acid (RNA) at week 48.

TAKEAWAY:

• At the start of the treatment, 31% of participants had > 100,000 copies/mL of HIV-1 RNA and 21% had a CD4 cell count < 200 cells/μL.
• At week 48, dolutegravir plus lamivudine demonstrated noninferiority to the three-drug regimen, with the percentage of participants having < 50 copies/mL of HIV-1 RNA being comparable in both the groups (difference, 2.6%; P = .034).
• Most participants achieved HIV-1 RNA < 50 copies/mL by week 4 with the percentage of participants achieving it being comparable in both the groups at all visits.
• No participant in the dolutegravir plus lamivudine group experienced virologic failure or any new drug-resistant mutations with adverse events being similar in both the groups.

IN PRACTICE:

“These findings provide evidence that resistance testing might not be a requirement for initiating treatment with a dolutegravir plus lamivudine two-drug regimen in regions or treatment situations with low frequency or suspicion of transmitted drug resistance mutations to lamivudine or integrase inhibitors,” the authors wrote.

“The present study supports the initiation of dolutegravir plus lamivudine in the absence of information on baseline resistance testing,” the author of an invited commentary wrote.

SOURCE:

This study was led by Ezequiel Cordova, MD, Fundación IDEAA, Buenos Aires, Argentina. It was published online on January 15, 2025, in The Lancet HIV.

LIMITATIONS:

The open-label design of this study may have introduced bias in the results and assessments of adverse events. The absence of information on initial resistance testing limited the assessment of drug efficacy in the presence of specific mutations. The results cannot be generalized to regions or populations with a higher prevalence of transmitted mutations to lamivudine or dolutegravir.

DISCLOSURES:

Few authors reported serving on advisory boards for, serving as investigators for, and receiving honoraria from ViiV Healthcare and several other pharmaceutical and healthcare companies. Other authors reported having no competing interests. The study was supported by ViiV Healthcare.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.