How Data From IAS 2019 on Dual Therapy May Soon Affect ART Guidelines

At the 10th IAS Conference on HIV Science in Mexico City, Mexico, compelling data on the use of 2-drug regimens for HIV treatment were presented that may significantly affect upcoming ART guideline revisions.

GEMINI: DTG + 3TC in the First-line Setting
Extended follow-up from the randomized, double-blind phase III GEMINI-1 and -2 studies comparing dolutegravir (DTG) plus lamivudine (3TC) with DTG plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) confirmed noninferiority of the 2-drug regimen. At Week 96, 86.0% of patients receiving DTG plus 3TC achieved HIV-1 RNA < 50 copies/mL compared with 89.5% with DTG plus FTC/TDF. Of more importance, no case of emergent resistance was observed through Week 96 among patients meeting criteria for virologic withdrawal. Therefore, DTG plus 3TC appears to be a safe and highly efficacious regimen for first-line ART, which might have important implications for lowering cost and preventing toxicity. As in other recent phase III trials investigating INSTI-based regimens, the number of late presenters included in the GEMINI studies was small, with only 8% of participants having a baseline CD4+ cell count ≤ 200 cells/mm³. Consequently, more data are still needed to characterize 2-drug and 3-drug INSTI-based first-line therapies in this patient subgroup that can be more challenging to treat.

TANGO: DTG/3TC as a Switch Strategy
The TANGO study was another important 2-drug ART study presented at IAS 2019, as it is the first to investigate the use of DTG/3TC in virologically suppressed patients. This ongoing randomized, open-label phase III trial demonstrated the noninferior efficacy of a switch to DTG/3TC vs continuing 3-drug or 4-drug tenofovir alafenamide (TAF)–based ART. By FDA Snapshot analysis, 0.3% of participants in the DTG/3TC arm vs 0.5% in the TAF-based ART arm experienced virologic nonresponse (ie, HIV-1 RNA ≥ 50 copies/mL) at Week 48. There were no cases of virologic withdrawal in the DTG/3TC arm, and the 1 case occurring with TAF-based ART was not accompanied by emergent resistance.

Clinical Implications of Dual Therapy
Positive results of both the GEMINI and TANGO studies will reposition national and international ART guideline recommendations around dual therapy. This will also have an impact on the uptake of this new dual therapy in Germany now that DTG/3TC is commercially available as of July 2019. However, future research will need to evaluate whether simplified 2-drug regimens will provide the additional benefit of reduced short-term or long-term toxicities, given that ART treatment remains lifelong. The potential cost savings associated with the need for fewer drugs promises price reductions for all HIV regimens. The hope is that this will help to increase access to ART for those in need of HIV treatment.

Looking Ahead
Do you anticipate integration of dual therapy in your practice? Join the discussion by posting a comment. For more details on this and other key issues from IAS 2019, review more Conference Coverage including CCO’s summary slidesets and downloadable audio from a series of live Webinars.