A Lower Dose of Efavirenz Works Just Fine -- and Why This Matters

February 23rd, 2014

A Lower Dose of Efavirenz Works Just Fine — and Why This Matters

As we heard last year in Malaysia, and now published in The Lancet, 400 mg of efavirenz is just as effective as the standard 600 mg dose.

The proportion of participants with a viral load below 200 copies per mL at week 48 was 94·1% for efavirenz 400 mg and 92·2% for 600 mg (difference 1·85%, 95% CI −2·1 to 5·79). CD4 T-cell counts at week 48 were significantly higher for the 400 mg group than for the 600 mg group (mean difference 25 cells per μL, 95% CI 6—44; p=0·01).

The 400 mg dose was better tolerated, too. For the record, these data are far more convincing than prior dose-reducing strategies with other antiretrovirals (stavudine, zidovudine, ritonavir come to mind). The results of the study were no doubt outstanding.

So these results have huge implications internationally, where efavirenz-based regimens are the default first-line choice for essentially all treatment naive patients. A lower dose will make treatment cheaper, coformulations easier, the pills smaller, and the sun will shine brighter, too.

Here in the USA? As of today, these data are of limited value, and here’s why:

As first-line therapy, efavirenz is overwhelmingly given as part of coformulated TDF/FTC/EFV (Atripla), which as you know includes 600 mg. Decreasing to 400 mg means increasing the number of pills, both because this splits up the coformulation and because EFV comes in 200 mg capsules.
If we’re after similar efficacy and better tolerability, there are several other non-efavirenz first-line options that do the same thing, and are easy to take, too — notably TDF/FTC/rilpivirine, TDF/FTC/elvitegravir/cobicistat, and TDF/FTC or ABC/3TC + dolutegravir.
Until a generic version of efavirenz is approved, there’s not all that much benefit from a cost perspective — though I do hear that TDF/FTC/EFV pricing has been going up.
The 400 mg dose is not FDA approved for treatment.

So for now, I stick with my opinion about the waning of the efavirenz era — a drug which has been on an extraordinary run dating back its approval in 1998.

However, if the 400 mg dose does get FDA approved, and if there are future coformulations with EFV using this dose, and if these data are confirmed to lower toxicity while maintaining virologic efficacy, then efavirenz might make a comeback.

But it’s a long shot.

HIV and ID Observations

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February 23rd, 2014