This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a randomized, double-blind comparison of three protease inhibitor (PI)-sparing regimens for the initial treatment of HIV infection with the goal being to suppress and maintain HIV-1 levels <200 copies/ml. The safety and tolerability of the 3 initial PI-sparing regimens will also be determined. The rationale for conducting this study is that current treatment guidelines recommend combination regimens of 2 nucleoside analogues with either a PI or a nonnucleoside reverse transcriptase inhibitor (NNRTI) as the preferred therapy for the initial treatment of HIV infection. However, the efficacy of current regimens is limited by their complexity, pharmacokinetic characteristics, short- and long-term side effects, and drug-resistance profiles at the time of virologic failure. Consequently, the identification of new initial regimens that are simpler, better tolerated, preserve treatment options in the event of virologic failure, and improve on antiretroviral potency is needed. In addition, recent concern over the long-term toxicities of PIs and the extensive cross-resistance among the available PIs have led to the testing of 'PI-sparing' regimens. The methodology consists of the following: Step 1: Patients are randomly selected to receive 1 of 3 blinded treatment regimens: abacavir (ABC)/lamivudine (3TC)/zidovudine (ZDV)/efavirenz (EFV), ABC/3TC/ZDV, or 3TC/ZDV/EFV. Patients with confirmed virologic failure on Step 1 and confirmed plasma HIV RNA levels of 10,000 copies/ml or greater must register to Step 2. Patients with confirmed virologic failure on Step 1 and plasma HIV RNA < 10,000 copies/ml may remain on Step 1 or register to Step 2. Step 2: Step 2 is open label. Regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with either EFV or BMS-232632. Based on genotypic resistance results, the NRTI combination may be a fixed-dose combination of 3TC/ZDV or 2 of the following: ZDV, didanosine (ddI), 3TC, stavudine (d4T), and ABC; however, the ZDV/d4T combination is not permitted. Clinical assessments and laboratory evaluations are done at entry, at Weeks 2, 4, 6, 8, 12, 16, 20, 24, and then every 8 weeks thereafter for the duration of the study. Evaluations are also required when a protocol-allowed drug substitution is made. In addition, 2 substudies are being conducted: a neurology substudy for efavirenz and a pharmacology substudy for BMS-232632.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000096-45
Application #
7378252
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2006-04-01
Project End
2007-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
45
Fiscal Year
2006
Total Cost
$10,030
Indirect Cost
Name
New York University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
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