Viral Dynamics and Pharmacokinetics of Abacavir and Tenofovir

• Status: Completed
• Trial end date: 2010-04-27
• Target enrollment: 0
• Participant gender: All

Summary

Once-daily nucleotide/nucleoside reverse transcriptase inhibitor (NtRTI/NRTI) combinations form the backbone of many regimens. Although efficacy data exists between tenofovir and the pyrimidine analogues (i.e. lamivudine and emtricitabine), recent clinical data suggests a potential interaction between tenofovir and purine analogs (i.e. abacavir and didanosine).

Specific Aim 1: To evaluate the impact of an acyclic nucleoside phosphonate, tenofovir (TDF), on the intracellular metabolism of a purine nucleoside analog, abacavir (ABC), as a determinant of the antiviral potency of this nucleotide/nucleoside reverse transcriptase inhibitor (NtRTI/NRTI) combination.

• Hypothesis #1: ABC and TDF dosed together will have reduced antiviral activity, as measured by early plasma HIV RNA decay kinetics, than the drugs given alone.

• Hypothesis #2: ABC dosed with TDF will have reduced intracellular concentrations, as measured by the ratio of carbovir triphosphate (active metabolite of ABC) to deoxyguanosine triphosphate (endogenous nucleotide), compared to ABC given alone.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: California Collaborative Treatment Group; University of California, San Diego
• Collaborators: GlaxoSmithKline; Santa Clara Valley Health & Hospital System; Santa Clara Valley Medical Center; University of California, Irvine; University of California, Los Angeles; University of Southern California; Universitywide AIDS Research Program
• Treatments: Abacavir; Dideoxynucleosides; Tenofovir

Criteria

Inclusion Criteria:

1. HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.

2. Antiretroviral naïve defined as no prior therapy.

3. CD4+ cell count > than 200 cells/ mm3 determined by site clinical laboratory within 90 days of screening.

4. HIV-1 RNA level > 5000 copies/mL obtained by site clinical laboratory within 90 days of screening.

5. Laboratory values obtained by screening laboratories within 30 days of entry:

• Absolute neutrophil count (ANC) ≥ 750/mm3.

• Hemoglobin ≥ 8.0 g/dL.

• Platelet count ≥ 50,000/mm3.

• Calculated creatinine clearance (CrCl) > 50 mL/min as estimated by the

• AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 5 x ULN.

• Total bilirubin ≤ 2.5 x ULN.

6. Negative serum or urine pregnancy test within 30 days of study entry.

7. Karnofsky performance score ≥ 70.

8. Men and women age ≥ 18 years.

9. Ability and willingness of subject to give written informed consent.

Exclusion Criteria:

1. Any NRTI or NNRTI-associated resistance mutations as defined by the updated International AIDS Society-USA (IAS-USA) mutation list.

2. Pregnancy and breast-feeding.

3. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.

4. Urgent need to initiate antiretroviral therapy, as determined by the patient's primary provider.

5. Serious illness (requiring systemic treatment and/or hospitalization) until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 14 days prior to study entry.

6. Use of any immunomodulator, HIV vaccine, or investigational therapy within 30 days of study entry.

7. Use of human growth hormone within 30 days prior to study entry.

8. Initiation of testosterone or anabolic steroids within 30 days prior to study entry. (Exception: Chronic replacement dosages in patient's with diagnosed hypogonadism is allowed)