Induction/Simplification With Atazanavir + Ritonavir + Abacavir/Lamivudine Fixed-Dose Combination In HIV-1 Infection
Status and phase
Conditions
Treatments
Details and patient eligibility
About
This study was designed to test the efficacy, safety, tolerability and durability of the antiviral response between atazanavir (ATV) + ritonavir (/r) + abacavir/lamivudine(ABC/3TC) Fixed dose combination (FDC) each administered once daily (QD) for 36 weeks followed by randomization to either a simplification regimen of ATV or continuation of ATV +/r for an additional 48 weeks, each in combination with ABC/3TC in antiretroviral (ART)-naive, HIV-1 infected, HLA-B*5701 negative subjects.
All subjects who complete the 84-week study will be eligible to enter the treatment extension phase and continue for an additional 60 weeks. The purpose of this extension is to obtain longer term treatment data in subjects who have completed the 84-week study.
Full description
Safety and Efficacy of an Initial Regimen of Atazanavir (ATV) + Ritonavir (/r) + the Abacavir/Lamivudine Fixed-Dose Combination Tablet (ABC/3TC FDC) for 36 weeks followed by Simplification to Atazanavir with ABC/3TC FDC or Maintenance of the Initial Regimen for an Additional 48 weeks in Antiretroviral-Naive HIV-1 Infected HLA-B*5701 Negative Subjects followed by an Optional 60-Week Treatment Extension Phase
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
- Subject is ≥ 18 years of age and has documented evidence of HIV-1 infection. (A female is eligible to enter and participate in this study if she is of: non child-bearing potential, child bearing potential with a negative pregnancy test and agrees to approved contraception methods, or agreement for complete abstinence.)
- Subject is antiretroviral-naïve (defined as having ≤14 days of prior therapy with any NRTI and no prior therapy with either a PI or NNRTI).
- Subject has plasma HIV-1 RNA ≥ 1,000 copies/mL by Roche COBAS AMPLICOR™ (Version 1.5) method at screening (if no other documentation of HIV infection is available, a positive result here may serve as documentation of HIV infection for this study).
- Subject is willing and able to understand and provide written informed consent prior to participation in this study.
Exclusion criteria
- Subject is HLA-B*5701 positive.
- Subject testing positive for Hepatitis B or both Hepatitis B and Hepatitis C at screening (+ HbsAg)
- Genotyping results performed at the screening indicate that the subject has any of the following mutations at the reverse transcriptase (RT) enzyme: K65R, L74V, or Y115F, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, or ≥ 3 of the following protease mutations associated with atazanavir resistance: D30, V32, M36, M46, I47, G48, I50, I54, A71, G73, V77, V82, I84, N88, and L90.
- Women who are pregnant or breastfeeding.
- Subject has an active or acute CDC Clinical Category C event at screening. Treatment for the acute event must have been completed at least 30 days prior to screening.
- Subject is, in the opinion of the investigator, unable to complete the 84-week dosing period and protocol evaluations and assessments.
- Subject has ongoing clinically relevant pancreatitis or clinically relevant hepatitis at screening.
- Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment.
- Subject suffers from a serious medical condition, such as diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction (including known, clinically significant cardiac conduction system disease, severe first degree atrioventricular block [PR interval > 0.26 seconds], second or third-degree atrioventricular block), which in the opinion of the investigator would compromise the safety of the subject.
- Subject has pre-existing mental, physical, or substance abuse disorder, which in the opinion of the investigator would interfere with the subject's ability to comply with the dosing schedule and protocol evaluations and assessments.
- Subject has a history of inflammatory bowel disease or malignancy, intestinal ischemia, malabsorption, or other gastrointestinal dysfunction, which may interfere with drug absorption or render the subject unable to take oral medication.
- Subject requires treatment with foscarnet, hydroxyurea or other agents with documented activity against HIV-1 in vitro within 28 days of study administration.
- Subject requires treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, vaccines, or interferons) within 28 days prior to screening, or subject had received an HIV-1 immunotherapeutic vaccine within 90 days prior to screening. Subjects using inhaled corticosteroids are eligible for enrollment.
- Creatinine clearance <50 mL/min via the Cockroft-Gault method [Cockroft, 1976].
- 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.
- Hypersensitivity to any component of the study drugs.
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN).
- Total bilirubin > 1.5 times the upper limit of normal (ULN).
- Subject has any acute laboratory abnormality at screening, which, in the opinion of the investigator, would preclude the subject's participation in the study of an investigational compound. Any grade 4 laboratory abnormality would exclude a subject from study participation.
- Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to screening, or has an anticipated need for these agents within the study period.
- Enrolled in one or more investigational drug protocols, which may have impacted HIV-1 RNA suppression.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
- Subjects requiring concomitant administration of proton pump inhibitors.
- Subjects who require treatment with the prohibited medications within 28 days of commencement of investigational product, or an anticipated need during the study.
Eligibility Criteria for Treatment Extension Phase:
-Subjects will be eligible to continue in the treatment extension phase (Weeks 84 to 144) if they have successfully completed the 84-week study.
Trial design
Primary purpose
Allocation
Interventional model
Masking
515 participants in 2 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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