{"id":10686,"date":"2023-05-25T17:28:00","date_gmt":"2023-05-25T21:28:00","guid":{"rendered":"https:\/\/blogs.nejm.org\/hiv-id-observations\/?p=10686"},"modified":"2023-05-26T05:40:56","modified_gmt":"2023-05-26T09:40:56","slug":"the-legacy-of-a-disappointing-hiv-clinical-trial-does-it-still-apply-to-hiv-today","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/the-legacy-of-a-disappointing-hiv-clinical-trial-does-it-still-apply-to-hiv-today\/2023\/05\/25\/","title":{"rendered":"The Legacy of a Disappointing HIV Clinical Trial — Does It Still Apply to HIV Today?"},"content":{"rendered":"

\"\"A long, long time ago, back in the early exciting days of raltegravir, the first HIV integrase inhibitor, we learned something important from a clinical trial with disappointing results. The trial bore the (barely) hidden name of the company that developed the drug — SWITCHMRK<\/a>, get it? — and had a profound impact on how we managed virologically suppressed patients for years.<\/p>\n

What did we learn? Namely, that it was risky to switch stable people from their “high resistance barrier” regimen of lopinavir\/ritonavir plus NRTIs to raltegravir plus NRTIs if they harbored viruses with NRTI resistance. Some of the participants who had a history of treatment failure who switched ended up experiencing virologic rebound with integrase inhibitor resistance, which made the switch to raltegravir not noninferior (sorry for the double negative) to continuing lopinavir\/ritonavir.<\/p>\n

The interpretation was that despite the potency and excellent tolerability of raltegravir — massively better than lopinavir\/ritonavir — it wasn’t enough to maintain viral suppression reliably unless the NRTIs were also fully active. Based on these results, for years we steered clear of use of this valuable drug class in any setting where we couldn’t use at least one other fully active drug.<\/p>\n

(My friend and colleague Joe Eron was the lead author on this study. I will note once again that Joe easily makes the top-5 in smarts in the HIV research world, no exaggeration, and that this was a very reasonable study design at the time, negative results notwithstanding. Unrelated, I wonder if Joe will attend this June 4 minor league baseball game in Charlotte<\/a>, called Joe-Nanza, which aims to assemble the largest number of Joes at any single sporting event in history. It’s just a 2-hour drive from Chapel Hill!)<\/p>\n

So now that we’ve reviewed SWITCHMRK, and a special event featuring Joes, let’s fast-forward to today, and contemplate a case. I’m sharing it with permission from Dr. Jezer Lezama, an ID doctor from Mexico who was looking for help<\/a> (case details slightly edited):<\/p>\n

PWH multi-drug resistance, w\/high level R to PIs, NRTIs, NNRTIs, only etravirine partially active in 2013 but w\/o previous exposure to integrase inhibitors. Rescue Tx: DRV600\/r BID + RAL + ETV with viral suppression since then. Simplify? To which regimen?<\/p><\/blockquote>\n

He provided the 2013 resistance genotype, and yes, this is a challenging virus:<\/p>\n

\"\"<\/p>\n

There’s a lot there to digest, so allow me to provide a quick interpretation, sparing you the trip to the Stanford HIV Drug Resistance Database<\/a>:<\/p>\n