No comparative trials have been done between three drug regimens employing two nucleosides plus a protease inhibitor versus two nucleosides plus a non-nucleoside reverse transcriptase inhibitor. Similarly, no comparative trials have been done between either of these regimens and four drug combinations of two nucleosides plus a protease inhibitor plus a non-nucloside reverse transcriptase inhibitor. Given that there may only be temporary usefulness for all current antiretrovirals, that both clinical and laboratory evidence of cross-resistance between protease inhibitors is appearing and novel toxicities are being observed with the use of certain regimens containing protease inhibitors, it is critical to see if this class of drug is most useful in initial or in rescue combination therapy. Six different regimens are to be employed in randomly selected subjects followed by cross over or salvage regimens among the treatments based on viral load endpoints or regimen intolerance. This will be a trial with 800 subjects. Study Objectives: 1) to compare 6 initial and follow up treatment strategies using dual nucleosides and either efavirenz, nelfinavir or both, for durable suppression of plasma HIV RNA. 2) to compare three and four drug strategies including dual nucleosides, efavirenz and/or nelfinavir for suppression of plasma HIV RNA. 3) to evaluate changes in CD4 cell counts over time. 4) to evaluate drug adherence. 5) to evaluate quality of life changes over time. 6) to evaluate the basis of regimen failure and suitable response to subsequent regimens through analysis of HIV gene mutations, SI phenotype and compliance.
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