Evaluation of 3TC or FTC Mono-therapy Compared to Continuing HAART as a Bridging Strategy
Condition: HIV Disease
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: HAART regimen; 3TC or FTC monotherapy
Intervention description: The study participant continued their non-suppressive HAART regimen as prescribed by their primary provider.; The study participant was assigned to either 3TC or FTC monotherapy (the choice of 3TC or FTC was left to the provider.
Intervention MeSH terms: Lamivudine; Emtricitabine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 8 Years
Maximum age: 24 Years
Healthy volunteers: No
Keywords: HIV; Bridging; Strategy

Summary:

      The purpose of this study was to compare the use of lamivudine (3TC) or emtricitabine (FTC)
      alone vs. continuing a failing highly active antiretroviral therapy (HAART) regimen in HIV
      infected children, adolescents and young adults. The study was to see if there were changes
      in the HIV virus and if there were differences in immune function, viral load and medication
      side effects between the two groups over 28 weeks. Participants were assigned to either take
      3TC or FTC alone or continue on his/her current failing HAART regimen. During the first 28
      weeks of this study, if the participant was randomized to the continue HAART arm, he/she was
      not switched to a different or new, potentially suppressive HAART regimen, but continued on
      the current failing HAART regimen. However, if continuing HAART, the participant might be
      switched to a new regimen if their provider felt that it was clinically needed or the
      participant met certain study endpoints (e.g., drop in CD4, increase in viral load).

      At the end of 28 weeks, the participant had the choice of remaining on the assigned study
      group medication(s) or starting a new HAART regimen prescribed by his/her doctor. Then, they
      would be followed for another 24 weeks to compare the difference in immune function, viral
      load and medication side effects between the different groups.
    

Eligibility criteria:

        Step 1 Inclusion Criteria:

          -  Age greater than or equal to 8 to less than 25 years of age, at study entry

          -  Documentation of HIV-1 infection defined as positive results from two samples
             collected at different time points

          -  Treatment experienced patients must have demonstrated failure on the current HAART
             regimen for 2 months or longer. These patients must have been on ARVs for at least a
             total of 6 months prior to entry. Thus, if the failing regimen was the first ARV
             regimen, then the patient must have been on that initial regimen for a minimum of 6
             months total.

          -  CD4+ T cell count greater than or equal to 100 cells/mm3 (confirmed on at least two
             occasions within 6 months of study entry, including the screening value)

          -  Documentation of the M184V mutation on genotypic testing at any time prior to study
             entry

          -  In the best judgment of the clinical site team, concerns about the subject's ability
             to adhere made it unsuitable to initiate a new optimal HAART regimen for at least 6
             months.

          -  Subject had not become adherent despite site's adherence interventions

          -  Female subjects of reproductive potential engaging in sexual activity that could lead
             to pregnancy had to agree to avoid pregnancy during the entire 52 week trial and to
             consistently and appropriately use at least two of the following contraception
             methods: condoms, diaphragm or cervical cap with spermicide, IUD, hormonal-based
             contraception. A list of acceptable methods can be found at the FDA Birth Control
             Guide (http://www.fda.gov/womens).

          -  Parent/legal guardian or subject able and willing to provide signed informed consent
             when applicable

        Step 1 Exclusion Criteria:

          -  Positive hepatitis B surface antigen or known active hepatitis B infection.

          -  Pregnant or breastfeeding.

          -  Active malignancy within the past 2 years.

          -  Current immunosuppressive therapy, including the equivalent of greater than 1
             mg/kg/per day or greater than 20 mg total daily dose of prednisone in the 2 weeks
             preceding screening. Subjects for whom long-term systemic corticosteroid therapy
             (greater than 2 weeks) was anticipated were excluded. [Note: non-steroidal
             anti-inflammatory agents and inhaled, nasal, and topical corticosteroids were not
             excluded as immunosuppressive therapy.]

          -  Prior immunization with an HIV-specific vaccine

          -  Greater than or equal to 1 CDC class C event within the past 12 months.

          -  Renal disease (as defined by estimated creatinine clearance less than 50 mL/min/1.73m2
             confirmed on two occasions within 3 months of screening).

          -  Active opportunistic infections, including active tuberculosis (TB).

          -  Current treatment for active systemic TB. If recent, infection must have completed
             treatment course. INH treatment for latent TB is allowed.

          -  Viral load greater than 250,000 copies/mL at screening.

          -  Known greater than or equal than Grade 3 of any of the following laboratory toxicities
             within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, AST,
             ALT, lipase, serum creatinine. Note: Subjects could be re-screened and enrolled if
             repeat value was less than Grade 3 without signs or symptoms of related organ
             dysfunction.

          -  Known greater than or equal to Grade 4 laboratory toxicities within 30 days prior to
             study entry, except with approval of the study team.

          -  For subjects who were not taking 3TC or FTC at the time of screening: Documented prior
             intolerance or adverse effect reasonably attributed to 3TC or FTC that resulted in
             permanent discontinuation.

          -  Problems with non-adherence attributed to modifiable structural barriers, such as lack
             of resources (e.g., insurance, transportation).

        Step 2 - Inclusion Criteria

          -  Met requirements for completion of Step 1

          -  Subject/guardian agree to continue participation in Step 2

          -  ViroSeq assay results had been received by site and reviewed by investigator