July 10th, 2009

Time for a Switch? What Actually Happened

A couple of months ago, I presented these three clinically stable, virologically suppressed patients — and asked if they should switch treatment:

  1. 50 year old man on ABC/3TC, EFV since 2000.  No renal disease.  Hyperlipidemia, on atorvastatin 80 mg a day.  Father died of an MI age 48.
  2. 63 year old man, on EFV + LPV/r for years; past history of neuropathy on d4T and 3TC.  Needs to go on inhaled steroids (preferably fluticasone) to help manage increasingly refractory asthma.
  3. 35 year old woman, on ABC/FTC, FPV/r BID — doing ok but missing some PM doses.

We also published them in AIDS Clinical Care, inviting both reader and and formal “expert” opinion.

Not surprisingly, there was disagreement from both the readers and the experts — some electing to change, some to switch, with various suggested new regimens.  It makes interesting reading, as all perspectives are defensible.

So what actually happened?  I switched them all:  Patient 1 is now on TDF/FTC/EFV, and Patient 3 on ABC/3TC, DRV/r.  They are both doing great.

Patient 2, um, not so much:  After switching to TDF/FTC/EFV, he almost immediately noted marked worsening in neuropathic symptoms — reminding me that in the bad old days of d4T and ddI, some patients did seem to experience worsening on 3TC.  So he went back on EFV + LPV/r, and the neuropathy returned to baseline over a month or so.

But — since he still needed the inhaled steroids for asthma treatment, and the fluticasone/PI interaction can be troublesome, I tried the combination of etravirine and raltegravir as a novel “NRTI- and PI-sparing” approach.  Almost immediately after this switch, he developed fevers, rigors, and malaise, and actually needed to be hospitalized overnight.

His current regimen?  Back to EFV + LPV/r — again doing well from the HIV perspective.  The pulmonologist managing his asthma is trying to get by with low dose beclomethasone, with some success.

Humbled, I’m reminded that this antiretroviral business can be tricky — and that sometimes, it’s better to do nothing than something.

3 Responses to “Time for a Switch? What Actually Happened”

  1. CM says:

    Interesting treatment dilemmas. Would you mind a couple of follow-up questions?

    For pt 3, what was the rationale for choosing DRV/r over daily boosted atazanavir, for example? Why not reserve DRV/r for when you need it in combination with an integrase and/or etravarine to replace a failing regimen? Are you using once daily DRV/r? If so, is that reliable in a PI experienced pt? If not, how does this switch help adherence? Finally, any concern about DRV/r resistance following a less than 100% adherent FPV/r regimen?

    For pt 2: “Almost immediately after this switch, he developed fevers, rigors, and malaise, and actually needed to be hospitalized overnight.”

    Can you expand on this a little? Was this thought to be a drug toxicity, OI, or somenthing else?

  2. Paul Sax says:

    Re #3: I am impressed about the efficacy and tolerability of QD DRV/r and very reassured that virologic failure (at least as shown in ARTEMIS) does not lead to significant PI resistance. Plus, FPV and DRV are quite similar chemically, so since she was tolerateing FPV, I went with DRV. I always use QD (as opposed to BID) DRV/r in patients without PI resistance — which I assumed was the case here since she was virologically suppressed, never had rebound, etc. Pharmacokinetics of QD DRV/r are outstanding (arguably better than QD FPV/r), and there will be data forthcoming on use of once-daily DRV/r in treatment experienced patients.

    Re#2: Definitely drug reaction. Not sure whether it was to ETR or RAL. Cleared up within 24 hours of stopping drugs.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

Biography | Disclosures | Summaries

Learn more about HIV and ID Observations.