Toxicity and drug exposure in a quadruple drug regimen in HIV-1 infected patients participating in the ADAM study

Objective: To study the relationship between toxicity and the exposure to n elfinavir and saquinavir as part of a quadruple drug regimen. Design: The ADAM study is a randomized study to; investigate the feasibilit y of induction-maintenance therapy in HIV-1 infection. Methods: HIV-l-infected patients with no prior use of antiretroviral treatm ent started induction therapy consisting of stavudine + lamivudine + nelfin avir + saquinavir for a period of 26 weeks. Data regarding toxicity of the quadruple regimen and exposure to the protease inhibitors were collected. Results: Seven of the 65 patients enrolled had to switch therapy for reason s of toxicity within the first 26 weeks. Diarrhoea was frequently reported (49 of 65, one discontinuation), but could be relieved by using antidiarrho eal agents. Laboratory monitoring revealed elevated liver enzymes (leading to four discontinuations) and mild to moderate elevations of triglycerides and cholesterol (nine and 23 of 65, respectively). The exposure to saquinav ir and nelfinavir was lower than expected. Abdominal pain was associated wi th a higher exposure to nelfinavir or: saquinavir. The association of nause a and abdominal distension with drug exposure appeared to vary over time. Conclusions: The quadruple drug regimen was quite well tolerated. Diarrhoea was frequently reported but could be relieved by the use of antidiarrhoeal agents. In comparison with other protease inhibitor combinations, lipid ab normalities in plasma were infrequent and mild. With the exception of diarr hoea, all gastrointestinal complaints observed were found to be associated with the level of exposure to nelfinavir or saquinavir. The exposure to the protease inhibitors was relatively low, although the virologic efficacy of the regimen used was satisfactory (C) 2000 Lippincott Williams & Wilkins.