Evolution of L74V or K65R Mutations in VIremic Subjects on Tenofovir Disoproxil Fumarate (TDF) or Abacavir (ABC) (EVITA)

Inclusion Criteria:

1. Confirmed first-time incomplete virologic suppression during treatment with at least 12 weeks of an ARV regimen consisting of TDF or ABC + FTC or 3TC + NNRTI or PI (TDF as Truvada or individually with FTC, and ABC as Epzicom or individually with 3TC). Confirmed first-time incomplete virologic suppression is defined as an initial plasma HIV-1 RNA response < 400 copies/mL, and subsequent virologic rebound > 400 copies/mL measured at two consecutive times.
2. Screening HIV-1 RNA < 20,000 copies/mL obtained within 30 days prior to study entry.
3. Screening CD4 cell count ≥ 200 cells/mL.
4. Screening HIV-1 genotype with M184V or at least one treatment-related primary mutation.

5. Routine labs as demonstrated by last available lab panel to be:

   • Hemoglobin > 8.0 g/dL;
   • Platelet count > 50,000/mm3;
   • AST (SGOT) < 210 U/L;
   • ALT (SGPT) < 240 U/L;
   • Alkaline phosphatase < 625 U/L;
   • Total bilirubin < 3.25 mg/dL; and
   • Calculated creatinine clearance ≥ 50 as estimated by the Cockcroft-Gault equation.
6. If participating in sexual activity that could lead to pregnancy, female study subjects must use two forms of contraception, one of which must be a barrier method.
7. Men and women aged ≥ 18 years.
8. Ability and willingness of subjects to give written informed consent.

Exclusion Criteria:

1. Subjects with screening HIV-1 genotype that is wild-type or contains the resistance mutations K65R/x or L74V/x.
2. Prior or current treatment with ARV regimen consisting of only NRTIs, ZDV or d4T, more than 2 NRTIs, ritonavir-boosted or dual PI regimen.
3. Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. Chronic treatment with prednisone at a daily dose of 10 mg or less is permitted. For non-serious illnesses, treatment of less than 21 days with larger doses of corticosteroids is permitted.
4. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
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 site investigator, for at least 7 days prior to study entry. NOTE: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) have no restrictions.
6. Unable to discontinue contraindicated current medications.