Considerations for more widespread use of 2-drug regimens to treat patients with HIV.
Grace McComsey, MD, FIDSA: John, quickly, your minute summary of 2-drug regimens. Do you think what we have available has an advantage to use, specifically dolutegravir/3TC, over other, more classic 3-drug regimens?
John Koethe, MD: The 2-drug regimens are a bit of a shift in the field. In 1996 data came out that the use of multiple drugs at one time was superior to a single drug for the treatment of HIV, and we had this idea of highly active antiretroviral therapy [ART]. It took a while to figure out whether that was 3 or 4 drugs, but eventually the field settled on 3, and it’s only recently that we’re making a shift toward 2 drugs. My personal sense is that the use of 2-drug regimens is something that’s going to continue to gain acceptance in the field, but it’s still a bit early right now. It should be noted, I mentioned before that there are 4 lead drug combinations recommended in the US guidelines for initial ART in people without special considerations. But one of those is the 2-drug regimen of dolutegravir and 3TC. That is a bit limited because again it’s not suitable for rapid start because you do need a genotype before you start that drug regimen to make sure that there’s no resistance to the lamivudine. You also don’t have good efficacy for hepatitis B. There is a need to check for that before. But in individuals where you can wait to start, it does look like it’s a very effective first-line ART agent. There’s a bit of lacking data for those with very high viral loads above 500,000 copies per mL. Below that level it seems to be quite effective. The additional value to this drug can also be in individuals who are treatment experienced as well. There has been a move toward the use of 2-drug regimens in people who already achieved viral suppression but who have a specific reason why you want to shift off of that 3-drug regimen.
Some of the other combinations would be dolutegravir/rilpivirine, and now that we have cabotegravir/rilpivirine injectables coming out, we’re really going to see an understanding and an embrace of 2-drug regimens, particularly as they’re used for long-acting therapy. In terms of the shifts, one of the most interesting things to come out recently has been the results of the TANGO study where we took individuals who were on TAF [tenofovir alafenamide]-containing regimens and switched them to dolutegravir/3TC. They did see a bit of improvement in some of their lipid parameters, particularly their triglycerides, and additionally, some of the HOMA-IR [homeostatic model assessment for insulin resistance], which is a measure of insulin resistance. We saw some decrease there, indicating maybe they were getting a bit more insulin sensitive coming off TAF. But it’s too early. It does show that there’s clearly a place for these 2-drug regimens for some patients.
Grace McComsey, MD, FIDSA: Thank you for watching this ContagionLive® Peer Exchange. If you enjoyed the content, please subscribe to the e-newsletter so you can receive upcoming Peer Exchanges and other great content. Thank you for listening.
Transcript Edited for Clarity