Because saquinavir levels are already low, it should probably not be given in combination with nevirapine, unless it is being combined with a drug that significantly increases saquinavir levels, such as ritonavir. Protease inhibitors do not alter nevirapine levels. A small trial using this combination demonstrated a 4 to 5 fold increase in saquinavir levels. However, marked increases in liver function tests were seen, and therefore a larger trial was not approved. This combination should be used with caution.
Delavirdine also increases levels of other protease inhibitors, especially indinavir and nelfinavir.
Ritonavir is a strong inhibitor of the cytochrome p450 system, leading to marked increases in the levels and half-lives of other protease inhibitors. Although the doses of the two agents varied initially, most participants are now taking 400 mg of each drug twice daily. The results remain impressive at 48 weeks, with viral loads remaining undetectable in most patients. Few have added nucleoside analogs, even though that option was open to them after 24 weeks. Those patients who had never taken antiretroviral therapy had better responses.