Recent research as suggested that use of the HIV medication abacavir (Ziagen, or
co-formulated with lamivudine as Epzicom) may increase risk for heart disease, though
findings from multiple studies have been inconsistent. This pilot study will examine
vascular function, a marker of heart disease risk, among patients taking abacavir as part of
their HIV medications and are then randomized to: 1) switch to tenofovir, another HIV
medication, or 2) continue to take abacavir.
Inclusion Criteria:
- Adult (≥18 years) males or non-pregnant females, non-lactating females.
- HIV-infected participants currently receiving fixed-dose abacavir/lamivudine based
regimen for ≥3 months preceding the screening visit.
- HIV-infection documented by a positive HIV-1 antibody (confirmatory western-blot) or
an HIV RNA level ≥1000 copies/mL
- Two consecutive plasma HIV RNA concentrations below the limit of detection for
clinical-based assays used for HCMC and ANW HIV clinics. The 1st HIV RNA
concentration must be at least 3 months prior to study entry.
- Subjects receiving lipid lowering agents will be allowed; however, dosing for these
medications must be stable for ≥3 months prior to study entry
- Adequate renal function defined as a calculated creatinine clearance (CLCr) ≥50
mL/min according to the Cockcroft-Gault formula:
- MALE: (140 - age in years) x (wt in kg) = CLCr (mL/min) 72 x (serum creatinine
in mg/dL)
- FEMALE: (140 - age in years) x (wt in kg) x 0. 85 = CLCr (mL/min) 72 x (serum
creatinine in mg/dL)
- Negative serum pregnancy test (females of childbearing potential only)
- Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN).
- Males and females (of childbearing potential) must agree to avoid pregnancy by sexual
abstinence, or utilization of a highly effective method of birth control throughout
the study period and for 30 days following discontinuation of study drug (refer to
Appendix A for definitions of 'childbearing potential' and 'highly effective method
of birth control')
Exclusion Criteria:
- Subjects with known resistance to abacavir, lamivudine, tenofovir DF, or
emtricitabine at anytime in the past (including but not limited to K65R, L74V/I,
M184V/I, or thymidine analog mutations).
- A new AIDS-defining condition diagnosed (with the exception of CD4 criteria) within
30 days of baseline
- Previous therapy with agents with systemic myelosuppressive, pancreatoxic,
hepatotoxic or cytotoxic potential within 3 months of study entry or the expectation
for such therapy at the time of enrollment
- Proven or suspected acute hepatitis in the 30 days prior to study entry
- Receiving ongoing therapy with any of the following (administration of any of the
following medications must be discontinued at least 30 days prior to the baseline
visit and for the duration of the study period):
- Nephrotoxic agents (aminoglycoside antibiotics, amphotericin B, cidofovir,
cisplatin, foscarnet, IV pentamidine, other agents with significant nephrotoxic
potential)
- Adefovir dipivoxil
- Probenecid
- Systemic chemotherapeutic agents (i. e., cancer treatment medications)
- Systemic corticosteroids
- Interleukin-2 (IL-2)
- Evidence of gastrointestinal malabsorption syndrome or chronic nausea or vomiting
which may confer an inability to receive an orally administered medication.
- Current alcohol or substance abuse judged by the investigator to potentially
interfere with subject adherence
- Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma.
Participants with biopsy-confirmed cutaneous KS are eligible, but must not have
received any systemic therapy for KS within 30 days of baseline and are not
anticipated to require systemic therapy during the study.
- Active, serious infections (other than HIV-1 infection) requiring parenteral
antimicrobial therapy within 15 days prior to screening.
- Prior history of significant renal or bone disease.
- Any other clinical condition or prior therapy that, in the opinion of the
investigator, would make the subject unsuitable for the study or unable to comply
with the dosing requirements.
- Known hypersensitivity to the study drugs, the metabolites or formulation excipients
