The main purposes of this study are: demonstrate the safety and efficacy of TPV/r among HCV or hepatitis B virus (HBV) co-infected HIV+population, three-class (NRTI, NNRTI, and PI) experienced, with documented resistance to more than one PI. Determine pharmacokinetic data in this co-infected population and potential utility of using therapeutic drug monitoring (TDM) in improving efficacy outcomes.
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Enrollment
11
Treatment Response at Week 48
Treatment response is a confirmed virologic response, defined as a viral load less than 50 copies/mL at two consecutive measurements at least 5 days apart, without death, permanent discontinuation, or introduction of a new antiretroviral
Time frame: 48 weeks
The Primary Safety Endpoint Was the Occurrence of Dose-limiting Hepatotoxicity During the Study.
Dose-limiting hepatotoxicity was defined as Grade 4 ALT or AST elevation confirmed in 48h or any evocative symptoms or signs of hepatitis, if it not clearly attributable to another cause. Patients who experienced dose-limiting hepatotoxicity stopped TPV/r and were considered treatment failures for the analysis.
Time frame: From the start of the study through 48 weeks.
Virologic Response Defined as Viral Load <50 Copies/mL at Each Visit
Virologic response defined as viral load less than 50 copies/mL
Time frame: After 4 weeks of treatment until the end of the trial
Occurrence of Viral Load Less Than 400 Copies/mL at Weeks 24 and 48
Patients with a viral load of less than 400 copies/mL at Weeks 24 and 48 as measured from a plasma sample.
Time frame: 24 and 48 weeks
Occurrence of Viral Load Less Than 400 Copies/mL at Each Visit
Patients with a viral load of less than 400 copies/mL at each visit as measured from a plasma sample.
Time frame: After 4 weeks of treatment until the end of the trial
Occurrence of ≥1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48
Occurrence of greater than or equal to 1 log10 drop in viral load from baseline at all visits, including visits at Weeks 24 and 48
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1182.99.32 Boehringer Ingelheim Investigational Site
Beverly Hills, California, United States
1182.99.31 Boehringer Ingelheim Investigational Site
Fort Lauderdale, Florida, United States
1182.99.12 Boehringer Ingelheim Investigational Site
Providence, Rhode Island, United States
1182.99.1 Boehringer Ingelheim Investigational Site
Austin, Texas, United States
1182.99.4 Boehringer Ingelheim Investigational Site
Houston, Texas, United States
1182.99.54001
Capital Federal, Argentina
1182.99.55002 Hospital DIA
Sacomã - São Paulo, Brazil
1182.99.55004 Unidade de Referência em doenças Infecciosas Preveníveis
Santo André, Brazil
1182.99.55001 Universidade Federal de Sao Paulo
São Paulo, Brazil
1182.99.55003 Centro de Referência e Treinamento - DST/AIDS
Vila Mariana - Sao Paulo, Brazil
...and 20 more locations
Time frame: Baseline, 24 and 48 weeks
Change in Viral Load From Baseline at Each Visit
Change in viral load (measured from a plasma sample) from baseline at each visitPatients with a viral load of less than 400 copies/mL at each visit as .
Time frame: After 4 weeks of treatment until the end of the trial
Time to Treatment Failure
For patients who never achieve a confirmed virologic response, time to treatment failure is defined as 0. For patients who achieve a confirmed virologic response, time to treatment failure is the earliest time of either: death, permanent discontinuation of the study drug or loss to follow-up, introduction of a new anti-retroviral drug to the regimen if it is not solely related to either toxicity or intolerance clearly attributable to a background drug, but not the study drug, or first occurrence of a VL \>50 copies/mL at two consecutive measurements after having achieved a VL \<50 copies/mL.
Time frame: After Day 1 of treatment until the end of the trial
Time to New AIDS or AIDS Related Progression Event or Death
Time to new AIDS or AIDS related progression event or death as defined by AIDS defining and/or AIDS-related illnesses.
Time frame: After Day 1 of treatment until the end of the trial
Change in CD4+ and CD8+ Cell Counts From Baseline to Week 48
Change from baseline to Week 48 for CD4+ and CD8+ cell counts. Samples were obtained for CD4+ and CD8+ as measurements of viral suppression during antiretroviral therapy.
Time frame: after 2 weeks of treatment till Week 48
Change in Ratio of CD38+/CD8+ From Baseline to Week 48
Change from baseline to Week 48 for the ratio of CD38+ to CD8+ cell counts. Samples were obtained for CD38+ and CD8+ as measurements of viral suppression during antiretroviral therapy.
Time frame: after 2 weeks of treatment till Week 48
Change in Ratio of CD3+ CD8+ CD38+ HLA DR From Baseline to Week 48.
Change from baseline to Week 48 for the ratio of CD3+ CD8+ CD38+ HLA DR . Samples were obtained for CD3+ CD8+ CD38+ HLA DR as measurements of viral suppression during antiretroviral therapy.
Time frame: after 2 weeks of treatment till Week 48
Tipranavir (TPV) and Ritonavir (RTV) Trough Concentrations at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
Tipranavir (TPV) and Ritonavir (RTV) trough concentrations from plasma samples at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
Time frame: after 2 weeks of treatment till Week 48
Patients Adherence With Study Medication Based on Pill Count
number of pills actually taken divided by the planned number of pills the patient should take
Time frame: After 4 weeks of treatment until the end of the trial
Occurrence of Tipranavir (TPV) Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured
A high inhibitory quotient (IQ), the ratio of trough plasma drug concentration to the protein-adjusted viral IC50, is a useful indicator of the potential efficacy margin of antiretroviral drugs. The IQ for TPV is calculated by the formula IQ = TPV Ctrough / (3.75 x Z x fold change of the patients virus), where Z = wild type control IC50 IIIB.
Time frame: After 2 weeks of treatment until the end of trial
Occurrence of Tipranavir (TPV) Trough Concentration >120 μM
Patients with TPV trough above 120 μM are at high risk of developing a Grade 3 or 4 ALT or AST elevations. The risk of Grade 3 or greater transaminase elevations appeared to be uniform at TPV trough concentration below 120 μM. Hence, for this study the TPV trough should be maintained below 120 μM.
Time frame: After 2 weeks of treatment until the end of trial
Post-dose Tipranavir (TPV) and Ritonavir (RTV) Concentrations at Week 4
Post-dose Tipranavir (TPV) and Ritonavir (RTV) plasma concentrations at Week 4
Time frame: Week 4
Frequency of Patients (%) With Possible Clinically Significant Abnormalities of Laboratory Measurements
Frequency of patients (%) with possible clinically significant abnormalities of laboratory measurements (haematology, differentials (automatic and absolute), coagulation, electrolytes, enzymes, substrates, urinalysis, serology and T-cells)
Time frame: Baseline through 48 weeks