Nelfinavir, a new protease inhibitor: early clinical results.

Nelfinavir is a potent inhibitor of the HIV-1 protease, which shows good inhibitory activity against HIV-1 in vitro. Initial clinical trials have shown that it has excellent activity in vivo in HIV-infected patients. The combination of 750 mg nelfinavir three times daily with zidovudine and lamivudine has been shown to cause a median reduction in HIV plasma RNA of approximately 2 log10 copies/ml, and to reduce plasma levels of RNA below the limit of detection (< 400 copies/ml) in 50-75% of patients after 12 months of treatment. This combination was associated with a mean increase of almost 200 CD4+ lymphocytes per mm3 at 12 months of therapy. The drug is well-tolerated, with mild diarrhea, which occurs in 12-20% of patients, being the most common side-effect. The pattern of initial protease mutations associated with nelfinavir resistance appears to be different from that seen with resistance to the other protease inhibitors, with the predominant initial mutation occurring at codon 30 of the HIV protease gene. Thus, initial trials indicate that nelfinavir is equivalent to other potent protease inhibitors and can be considered as a component in first-line combination therapy for HIV-infected patients.