Atazanavir (BMS-232632) in Combination With Ritonavir or Saquinavir, and Lopinavir/Ritonavir, Each With Tenofovir and a Nucleoside in Subjects With HIV
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Atazanavir + ritonavir + tenofovir + nucleoside; Atazanavir + saquinavir + tenofovir + nucleoside; Lopinavir/ritonavir + tenofovir + nucleoside
Intervention description: Active Comparator, Capsules, tablets, Oral; Active Comparator, Capsules, tablets, Oral; Active Comparator, Capsules, tablets, Oral
Intervention MeSH terms: Ritonavir; Lopinavir; Atazanavir Sulfate; Saquinavir; Tenofovir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 571.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to learn how well atazanavir (ATV) works in combination with
      ritonavir (RTV) or saquinavir (SQV) with tenofovir (TDF) and a nucleoside to reduce the viral
      load of treatment experienced subjects with human immunodeficiency virus (HIV). There is a
      comparison arm with lopinavir (LPV)/RTV and TDF and a nucleoside.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Virologic failure to 2 or more highly active antiretroviral therapy (HAART) regimens
             that, in total, have included at least one drug from all approved classes protease
             inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse
             transcriptase inhibitors (PI, NNRTI, NRTI):

               1. Currently on a failing HAART regimen with 2 qualifying plasma viral load
                  measurements (hospital/clinic value within 4 weeks of screening with viral load
                  equivalent to =>1,000 c/mL on the Roche Amplicor[TM] and central lab measurements
                  of =>1,000 c/mL (Roche Amplicor[TM]) within 4 weeks of randomization

               2. Cluster of Differentiation 4 (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 Quantiplex branched DNA (bDNA) assay

          -  Both females of child bearing potential and males must utilize effective barrier
             contraception to reduce transmission of sexually transmitted disease, including human
             immunodeficiency virus (HIV). Other contraception in addition to barrier methods is
             permitted; interaction between atazanavir and oral contraceptives has 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:

               1. serum creatine <1.5 times the upper limit of normal (ULN)

               2. total serum lipase <1.4 times the ULN

               3. liver enzymes alanine aminotransferase (AST), aspartate aminotransferase (ALT) <3
                  times the ULN

               4. total serum bilirubin <1.5 times the ULN

        Exclusion Criteria:

          -  Prior use (=>3 days) of atazanavir, TVF or LPV/RTV; if history 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 <3 x ULN

          -  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 of therapy with methadone or
             ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect
             Cytochrome P450 3A4 (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:

               1. Heart rate-corrected QT (QTc) interval >450 msec on the screening
                  electrocardiogram (EKG)

               2. Heart rate <40 beats per minute (bpm)

               3. Pause length >3 seconds seen on EKG

               4. Clinical symptoms potentially related to heart block

               5. Third degree heart block

          -  History of acute or chronic pancreatitis

          -  If choosing 2'-3' dideoxyinosine (ddI) or 2',3'-didehydro-3'-deoxythymidine (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.