SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavir/r IN Race/Gender HIV+ Patients Randomized to TDM or SoC
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: tipranavir; ritonavir; Optimized Background Regimen (OBR)
Intervention description: Patients received between two and four active anti-retroviral medications based on resistance testing results, as background treatment, and remained on these for the duration of the trial.
Intervention MeSH terms: Ritonavir; Raltegravir Potassium; Maraviroc; Tipranavir; Enfuvirtide; Reverse Transcriptase Inhibitors
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary purpose of this study is to:

        1. Demonstrate the safety and efficacy of tipranavir/ritonavir (TPV/r) among a racially
           diverse HIV+ population (males and females) who are three-class (nucleoside reverse
           transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI),
           and protease inhibitor (PI)) experienced with documented resistance to more than one PI.

        2. Determine pharmacokinetic data in this racially and gender diverse population.

        3. Determine the potential utility of using therapeutic drug monitoring (TDM) in improving
           efficacy outcomes.
    

Eligibility criteria:

        Inclusion Criteria:

        Main inclusion criteria for the study are:

          1. HIV-1 infected adults, men and women at least 18 years of age.

          2. 3-class (nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse
             transcriptase inhibitor (NNRTI), and protease inhibitor (PI)) treatment-experienced
             (min of 3-months duration for each class) with resistance to more than one PI (on
             screening resistance testing). NNRTI-naïve patients who have genotypically documented
             NNRTI-resistance mutations on past or screening resistance testing would be eligible.

          3. CD4+ T lymphocyte count >=50 cells/mm3.

          4. HIV-1 viral load >=1,000 copies/mL at screening.

          5. The antiretroviral (ARV) study treatment regimen must consist of TPV/r in combo with
             an optimized background regimen (OBR) of 2-4 agents: N(t)RTIs (NRTI or NtRTI),
             enfuvirtide (ENF), and/or, where available, a trial approved expanded access program
             (EAP) investigational agent.

          6. Acceptable screening laboratory values that indicate adequate baseline organ function.

          7. Acceptable medical history with a chest X-ray without evidence of active disease and
             an electrocardiogram (ECG) without clinically important abnormalities within one year
             of the study.

          8. A reliable method of barrier contraception will be used by all female patients who are
             of childbearing potential.

        Exclusion Criteria:

        Main exclusion criteria for the study are:

          1. Known hypersensitivity to the tipranavir (TPV) or ritonavir (RTV).

          2. ARV medication naïve.

          3. Genotypic resistance to TPV (defined as a TPV mutation score >7).

          4. Patients on recent drug holiday, defined as off antiretroviral (ARV) medications for
             at least 7 consecutive days within the month prior to screening.

          5. Prior tipranavir use.

          6. Inability to adhere to the requirements of the protocol.

          7. Patients with prior history of hemorrhagic stroke or intracranial aneurysm.

          8. Patients with a history of ischemic stroke, neurosurgery or skull trauma within 4
             weeks prior to screening.

          9. History of Progressive Multifocal Leukoencephalopathy, Visceral Kaposi's Sarcoma,
             and/or any malignancy.

         10. Any acquired immunodeficiency syndrome (AIDS) defining illness that is unresolved,
             symptomatic or not stable on treatment for at least 12 weeks at screening visit.