The purpose of this study is to learn how well atazanavir works in combination with ritonavir or saquinavir with tenofovir and a nucleoside to reduce the viral load of treatment experienced subjects with HIV. There is a comparison arm with lopinavir/ritonavir and tenofovir and a nucleoside.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: atazanavir	Phase III

Ages Eligible for Study:  16 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Virologic failure to two or more HAART regimens that, in total, have included at least one drug from all approved classes (PI, NNRTI, NRTI):

a. Currently on a failing HAART regimen with two qualifying plasma viral load measurements (hospital/clinic value withing 4 weeks of screening with viral load equivalent to =/>1,000c/mL on the Roche Amplicor[TM] and central lab measurements of =/>1,000C.mL (Roche Amplicor[TM]) within 4 weeks of randomization

b. CD4 cell count =/>50 cells/mm3 obtained within 4 weeks prior to randomization

• =/> 16 years of age (or minimum age as determined by local regulations or as legal requirements dictate);
• History of prior virologic response to at least one HAART regimen, defined as a 1.0 log10 decline or a decline in viral load to< 400 C/mL by Roche Amplicor or <500 c/mL by Chiron bDNA
• Both females of child bearing potential and males must utilize effective barrier contraception to reduce transmission of sexually transmitted disease, including HIV. Other contraception in addition to barrier methods is permitted (but see last paragraph Section 5.2.1); interaction between atazanavir and oral contraceptives have not been studied.
• Subjects must be able to provide written informed consent;
• Subjects should be available for follow-up for a period of at least 48 weeks
• Baseline laboratory values measured within 2 weeks prior to initiating study drugs as follows:

a. serum creatine <1.5 times the upper limit of normal

b.total serum lipase < 1.4 times the upper limit of normal

c. liver enzymes (AST, ALT) < 3 times the upper limit of normal

d. total serum bilirubin < 1.5 times the upper limit of normal

Exclusion Criteria:

• Prior use (=/>3 days) of atazanavir, TVF or LPV/RTV; if hx of SQV then must be phenotypically sensitive
• the current failing antiretroviral regimen must have been administered for at least eight weeks at he initiation of screening and must not include both a PI and NNRTI
• Presence of a newly diagnosed HIV-related opportunistic infection or any medical requiring acute therapy at the time of enrollment
• Proven or suspected acute hepatitis in the 30 days prior to study entry. Subjects with chronic hepatitis are eligible provided that their liver function enzymes (ALT/AST) are <3xULN
• Previous therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatoxic, hepatoxic or cytotoxic potential within 3 months of study start or the expected need for such therapy at the time of enrollment ot therapy with methadone or ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect CYP3A4.
• Active alcohol or substance use sufficient, in the Investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis
• Intractable diarrhea (=/> 6 loose stools/day for at least 7 days consecutive days) within 30 days prior to study entry
• Pregnancy or breast-feeding
• History of hemophilia
• Presence of cardiomyopathy
• Any one of the following:

a. QTc interval > 450 msec on the screening EKG

b. Heart rate < 40 bpm

c. Pause length > 3 seconds seen on EKG

d. Clinical symptoms potentially related to heart block

e. Third degree heart block

• History of acute or chronic pancreatitis
• If choosing ddI or d4T as the NRTI: History or signs and symptoms of bilateral peripheral neuropathy =/> Grade 2 at the time of screening
• Inability to tolerate oral medications
• Any other clinical conditions or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for study or unable to comply with the dosing requirements.

California
      Torrance,  California,  90502,  United States
      San Francisco,  California,  94121,  United States
Colorado
      Boulder,  Colorado,  80304,  United States
Florida
      Altamonte Springs,  Florida,  United States
      Orlando,  Florida,  32801,  United States
      Miami Beach,  Florida,  33160,  United States
      Ft. Lauderdale,  Florida,  33308,  United States
      Ft. Lauderdale,  Florida,  33306,  United States
Georgia
      Decatur,  Georgia,  United States
Hawaii
      Honolulu,  Hawaii,  96816,  United States
Indiana
      Boise,  Indiana,  United States
Kansas
      Wichita,  Kansas,  67214,  United States
Kentucky
      Louisville,  Kentucky,  40202,  United States
Louisiana
      New Orleans,  Louisiana,  United States
Massachusetts
      Brookline,  Massachusetts,  United States
      Fall River,  Massachusetts,  02720,  United States
New Jersey
      East Orange,  New Jersey,  United States
      Newark,  New Jersey,  07103,  United States
New York
      Rochester,  New York,  14620,  United States
      Buffalo,  New York,  14215,  United States
      New York,  New York,  10019,  United States
      Manhasset,  New York,  11030,  United States
North Carolina
      Huntersville,  North Carolina,  28078,  United States
      Winston Salem,  North Carolina,  27157,  United States
      Winston Salem,  North Carolina,  29203,  United States
Ohio
      Akron,  Ohio,  United States
Texas
      Dallas,  Texas,  75246,  United States
      Dallas,  Texas,  United States
      Houston,  Texas,  77006,  United States

Study ID Numbers:  AI424-045
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  May 6, 2002
ClinicalTrials.gov Identifier:  NCT00035932
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08