#viramune

The pharmacokinetics of nevirapine support taking both tablets at the same time, although the company never bothered to get that dose approved since they were developing the long acting 400 mg formulation. (Is that an option?) 

An old trial compared 200 mg twice daily vs. 400 mg once daily (before the availability of the long-acting version). The once daily dose was just as effective but had more early toxicity. However, this was a study of initial therapy. Since most nevirapine toxicity occurs in the first few weeks, it’s not surprising that you might see differences during that time period. In people who are already tolerating nevirapine, you wouldn’t expect to see toxicity with a switch to 400 mg daily, and this switch was commonly made in the U.S. back when we used to use nevirapine. 

No, not exactly. While it’s true that nevirapine has more liver toxicity than efavirenz, the toxicity occurs in the first months of therapy. If you’ve been on it for for almost 3 years, you’re out of danger. 

As for resistance, it’s also true that failure of nevirapine can lead to broader cross-resistance within the NNRTI class than failure of efavirenz, but resistance only happens if you fail.  You’ve been taking it for 3 years without failure, so resistance doesn’t sound like an issue.

The combination of Combivir and Viramune is not a standard regimen in the U.S., but you didn’t say where you were writing from—a critical piece of information that almost everyone leaves out. Nausea and fatigue are common side effects of the AZT in Combivir. 

In the U.S., four of the five recommended regimens include integrase inhibitors and the fifth is a protease inhibitor-based regimen. Neither Combivir nor Viramune is recommended anymore. 

The effectiveness is probably similar, but nevirapine can have more severe early toxicity, including serious liver and skin toxicity. In a head-to-head comparison trial (2NN), nevirapine was “not non-inferior” to efavirenz, which is a confusing statistical way of saying that it failed to meet the criteria for non-inferiority (comparability), probably due to early nevirapine toxicity.

Nevirapine toxicity is an even more important issue today than it was in the past. Since nevirapine toxicity is a hypersensitivity reaction, it is more likely to occur if your immune system is relatively healthy. We’re now treating people at higher CD4 counts than we used to, and the higher your CD4 count is, the greater the risk of toxicity. Nevirapine toxicity tends to occur during the first 4-6 weeks of therapy. After that, it becomes a safe and well tolerated drug.