September 4th, 2011

“Novel” Approaches to Initial HIV Therapy: Part II

Two studies were just published on alternative strategies for initial HIV therapy. I’ve already reviewed the first one here.

The second paper is a single-arm (n=112) study of darunavir/r (once daily) plus raltegravir, the latest riff on the “NRTI sparing” approach.

As I mentioned when I first covered this study, the high rate of virologic failure — 26% overall, and a whopping 43% (21 of 49) with viral loads > 100,000 — came as a complete shock. In fact, I would have bet good money that this regimen would work just fine. (Glad I’m not a betting man — except in poker.) Five of the 28 virologic failures developed integrase resistance, all of them from the high VL stratum.

Why is this so surprising? You have the antiviral potency of raltegravir plus the high genetic resistance barrier of boosted darunavir — so what went wrong?

The study authors offer some possible explanations for these disappointing results (suboptimal adherence, asymmetrical dosing, lowered darunavir concentrations from raltegravir, minority variants resistant to raltegravir), but the bottom line is that this regimen just didn’t work very well. A fully-powered comparative study (darunavir/r plus raltegravir or TDF/FTC) is ongoing in Europe; I’m sure their DSMB is keeping a close eye on the results.

So two non-standard approaches to initial HIV therapy, with TDF/FTC + etravirine looking promising, and darunavir/r + raltegravir much less so.

2 Responses to ““Novel” Approaches to Initial HIV Therapy: Part II”

  1. Richard says:

    Great post !
    Does this finding give you any pause with regard to prescribing darunavir-ritonavir + raltegravir (+ some third agent) as salvage ART in patients with high viral loads if 2-3 other potentially fully active drugs are available?


    • Paul Sax says:


      Not really — the combination of darunavir/r plus raltegravir (plus at least one other active drug) was an absolute miracle in our heavily treatment-experienced patients in the late 2000s. So lots of good experience with it.

      Still not quite sure why this regimen failed — maybe we should just accept we need 3 active drugs for optimal efficacy, and move on …


HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

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