SALVAGE ANTIRETROVIRAL THERAPIES

Tulane University Of Louisiana, New Orleans LA

Investigators

Linked publications & trials

Abstract

A pressing question in the treatment of HIV-infected individuals is whether clinical cross-resistance exists among currently available protease inhibitors. Treatment with nelfinavir selects for nelfinavir-resistant HIV variants that do not exhibit in vitro cross-resistance to other protease inhibitors including saquinavir, ritonavir, indinavir, and amprenavir. The lack of in vitro cross-resistance to other protease inhibitors and the restricted pattern of resistance substitutions has led to the widespread use of nelfinavir for initial therapy due to a perceived lack of resistance to other protease inhibitors. However, there are no definitive clinical data to support or refute this. Specifically, the magnitude and duration of virological response to treatment regimens containing other protease inhibitors in individuals in whom nelfinavir has failed to maintain virus suppression has not been determined. The study design is a Phase II, randomized, open-label, 4-arm trial comparing dual and single protease inhibitor salvage antiretroviral therapies for HIV infected subjects who have virologic evidence of nelfinavir treatment and who are naive to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Patients are also naive to both components of at least one of the following NRTI combinations: 1) ZDV and 3TC; 2) d4T and 3TC; 3) d4T and ddI; or 4) ZDV and ddI. Eligible subjects will be randomized in an open-label fashion to the treatment arms. The randomization is as follows: ARM A: Ritonavir 400 mg BID + Saquinavir 800 mg BID + Efavirenz 600 mg QD + 2 new NRTIs; ARM B: Indinavir 1000 Q8 hours + Efavirenz 600 mg QD + 2 new NRTIs; ARM C: Amprenavir 1200 mg BID + Efavirenz 600 mg QD + 2 new NRTIs; ARM D: Indinavir 1200 mg BID + Amprenavir 1200 mg BID + Efavirenz 600 mg QD + 2 new NRTIs. Plasma HIV RNA will be quantified in real time and the study monitored closely for early virologic endpoints