Can 2-Drug Regimens be Used for Rapid-Start ART?

Rapid start is a linkage-to-care best practice where patients are seen and started on antiretroviral therapy (ART) as soon as possible after HIV diagnosis. Endorsed by both the US Department of Health and Human Services and International AIDS Society guidelines, it is now the standard of care. For this reason, I am very excited that clinical trials are incorporating this model and recognizing its importance.

STAT Study: Rapid Test and Treat With DTG/3TC in Adults With Newly Diagnosed HIV
The STAT study is a single-arm intervention where 131 newly diagnosed patients started on dolutegravir (DTG)/lamivudine (3TC) before receiving their baseline labs or HIV genotype. At Week 48, 97% (107/110) of patients were suppressed (HIV-1 RNA <50 copies/mL), excluding patients lost to follow-up on any ART regimen. The FDA snapshot at 48 weeks―which included patients lost to follow-up, switched from DTG/3TC, and failures―was lower at 76% (100/131). Two participants had virologic failure but did not develop any resistance to DTG or 3TC.

Ten patients had HIV-1 RNA >1 million copies/mL, and the regimen was effective. This is important because patients with HIV-1 RNA >500,000 copies/mL were excluded from the GEMINI-1 and GEMINI-2 clinical trials, which evaluated the efficacy of DTG/3TC in treatment-naive adults with HIV.

Applying the Results to My Own Practice
The STAT trial results are informative, but I have concerns as they relate to my own patient population. First, DTG/3TC is not a fully active regimen against hepatitis B virus (HBV), so patients with HBV coinfection (5%) had their ART modified to a fully active combination after labs were received. In my practice, the rate of HBV coinfection is 10%, twice the rate in this trial.

Furthermore, in the STAT trial, 1 patient with an M184V mutation switched to DTG/rilpivirine following review of baseline genotype. In my practice, 7% of my newly diagnosed patients have a baseline M184V mutation, much higher than seen in this trial.

To me, the initial visit for rapid start is such an important time to develop long-term trust between me and my newly diagnosed patient. It is essential to explain the safety and effectiveness of our current regimens and to communicate the vitally important U = U message. I am hesitant about starting a rapid ART regimen of 2 drugs that I will need to broaden to 3 drugs if the patient turns out to have HBV coinfection or an M184V mutation. I am concerned about how switching therapy would impact my developing relationship with my patient.

Furthermore, demonstration of projects such as my own and at UCSF have shown much higher rates of viral suppression at 48 weeks. I cannot explain the 16% loss to follow-up in the STAT trial.

Going to the Guidelines
Of most importance, rapid start is an intervention grounded in equity, ensuring that all patients are started immediately after diagnosis on first-line, guideline-endorsed ART. There have been longstanding disparities in time to the initiation of ART, and therefore I am committed to implementing rapid start, and I applaud clinical trials that incorporate this model.

That said, there also have been disparities in the use of first-line, guideline-approved regimens. So until evaluated and endorsed by our guidelines for rapid start, I recommend sticking with the recommended regimens.

Your Thoughts?
Do you anticipate using DTG/3TC for rapid initiation in your practice based on the STAT data? Answer the polling question and join the discussion by posting a comment.