The Switch Study: The Role of Lamivudine/Emtricitabine (3TC/FTC) in Antiretroviral Regimens

In this randomized, open-label, controlled trial, HIV-infected patients who are failing 3TC/FTC-containing highly active antiretroviral therapy, (HAART), will be offered individual treatment selection based on best clinical judgment and genotypic HIV-RNA resistance analysis. Patients who meet entry criteria will first be randomized to either continue or discontinue 3TC/FTC while they remain on their current therapy. HIV-1 viral load will be measured 4 times over a period of 14 days to determine the virologic response to this change. At day 14, each patient's regimen will be optimized to a new combination based on a genotype test taken at study entry. Patients will then start on the new salvage regimen, including or not including 3TC/FTC based on their initial randomization. Additional HIV-1 viral load measurements will be obtained to determine the virologic response to the new salvage regimen over 24 weeks.

Inclusion criteria

• HIV-1 seropositive patients >= 18 years of age
• Willingness and ability to understand and sign a written informed consent and comply with the protocol procedure
• Prior treatment with nucleoside reverse transcriptase inhibitors (NRTI's), non-nucleoside reverse transcriptase inhibitors (NNRTI's) and protease inhibitor (PI)-containing regimens
• On a stable PI and 3TC or FTC -containing regimen for >= 2 months
• Plasma HIV-1 RNA >5000 copies/ml
• CD4 >100
• Documented M184V or I on genotype within 3 months of study entry
• At least 3 PI-associated resistance mutations on genotype within 3 months of study entry, (including known resistance mutations at codons 10, 30, 46, 50, 54, 71, 82, 84, and 90)

Exclusion criteria

• In the opinion of the investigator a patient that is either unwilling or unable to be adherent to antiretroviral drugs
• Requirement for concomitant treatment with medicines that interfere with the therapy prescribed in the study
• Patients who have never taken 3TC or FTC, or with no prior documentation of the M184V mutation
• Active hepatitis B infection
• Vaccination within 2 weeks of entering the study
• An acute opportunistic illness within 4 weeks of entering the study; chronic infections will not be excluded
• Use of immunomodulatory medications such as IL-2
• Planned use of enfuvirtide, (T20) in salvage regimen, (in T20 naïve subjects)