Phase 2
Completed N=21
Viral Dynamics and Pharmacokinetics of Abacavir and Tenofovir
Source: ClinicalTrials.gov NCT00214890 ↗Enrolled (actual)
21
Serious AEs
0.0%
Results posted
Mar 2021
Primary outcomePrimary: Change in Short-term Virologic Response — -.11; -.15; -.16; -.16 log(10) copies/mL per day
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Short-term Virologic Response |
-.11; -.15; -.16; -.16 | — |
| PRIMARY Compare the Plasma Data of the Two Monotherapy Regimens to the Dual NRTI Regimen |
3.82; 12.54; 4.09; 13.62 | — |
| PRIMARY Compare the Intracellular Pharmacokinetic (PK) Data of the Two Monotherapy Regimens to the Dual NRTI Regimen |
49.3; 72.2; 108.1; 80.9 | — |
| SECONDARY Evaluate Change in Cellular Regulatory Enzymes Involved With Nucleoside Analogue Transport Across Cell Membranes as Assessed by RT-PCR of Specific mRNA Transcripts |
4026; 2464; 3238; 3314 | — |
| SECONDARY Determine Total Number of NRTI-associated Mutations After 7 Days of ABC or TDF Monotherapy or After 7 Days of Dual NRTI Therapy With ABC + TDF |
0; 0 | — |
| SECONDARY Compare the Relative Viral Potency of TDF Monotherapy Versus ABC Monotherapy |
-0.11; -0.15 | — |
Eligibility Criteria
Inclusion Criteria
- 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.
- Antiretroviral naïve defined as no prior therapy.
- CD4+ cell count > than 200 cells/ mm3 determined by site clinical laboratory within 90 days of screening.
- HIV-1 RNA level > 5000 copies/mL obtained by site clinical laboratory within 90 days of screening.
- 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.
- Negative serum or urine pregnancy test within 30 days of study entry.
- Karnofsky performance score ≥ 70.
- Men and women age ≥ 18 years.
- Ability and willingness of subject to give written informed consent.
Exclusion Criteria
- Any NRTI or NNRTI-associated resistance mutations as defined by the updated International AIDS Society-USA (IAS-USA) mutation list.
- Pregnancy and breast-feeding.
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
- Urgent need to initiate antiretroviral therapy, as determined by the patient's primary provider.
- 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.
- Use of any immunomodulator, HIV vaccine, or investigational therapy within 30 days of study entry.
- Use of human growth hormone within 30 days prior to study entry.
- 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)
Data sourced from ClinicalTrials.gov (NCT00214890). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.