Evaluation of 3TC or FTC Mono-therapy Compared to Continuing HAART as a Bridging Strategy

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