Can nevirapine be safely substituted for other agents in those with high CD4 cell counts and virologic suppression?

Michael Dube, for

This question was addressed by the observational Dutch cohort study ATHENA, presented by Ferdinand Wit. The concern of course is when nevirapine is started in ART-naive patients with high CD4 cell counts (>250 females, >400 males) there is excessive hepatotoxicity which can be severe. But does this carry over to individuals who are already virologically suppressed, and are switched to nevirapine?

One published study from the EuroSida cohort (Antiviral Therapy 12:335, 2007) showed that switching to nevirapine with high CD4 cell counts was significantly safer in ART-experienced patients than in ART-naives. This was particularly true during the first 3 months of therapy.

The presentation from ATHENA reached similar conclusions. Those with low CD4 cell counts when ART was initiated, but who had high CD4 counts at the time of switching, tolerated the switch to nevirapine as well as ART-naive subjects with low CD4 counts whose initial therapy included nevirapine.

These observational data provide some additional comfort to those patients with virologic suppression and now have high CD4 counts who are considering a switch to nevirapine. It is possible though, that some of the hypersensitivity reactions seen in the ART-naive patients are due to newly started medications other than nevirapine, so that these reactions may be relatively over-reported and attributed to nevirapine.

Said otherwise, ART-experienced patients who switch may actually have higher rates of nevirapine reactions – but since they may only be starting one new drug, this is not confounded by their other medications and only “true” nevirapine reactions get counted.

A switch to nevirapine should still be always considered potentially risky and be monitored closely, until a randomised controlled trial more definitively establishes the safety of this sort of switch approach.


It should be added that these patients had undetectable viral load at the time of the switch.

No information was provided about the choice of dosing, and whether patients switched to the full nevirapine dose or whether they use the 200mg once-daily dose for the first two weeks. There is still no clear evidence to inform this decision.


Wit F et al. Incidence of hypersensitivity reactions associated with nevirapine-containing HAART in patients with prior treatment experience may differ from that in treatment-naive patients: the ATHENA cohort study.

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