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

HIV Infections Clinical Trial

Official title:

The Role of 3TC/FTC in Partially Suppressive Antiretroviral Regimens: The Switch Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00152061
• Other study ID #: 74009
• Secondary ID: IRB protocol 740
• Status: Completed
• Phase: N/A
• First received: September 8, 2005
• Last updated: June 18, 2013
• Start date: January 2005
• Est. completion date: August 2005

Study information

• Verified date: June 2013
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

In this study the researchers will be enrolling patients who are failing their current antiretroviral regimen who also have resistance to 3TC or FTC. Patients will have their current antiretroviral regimen changed based on resistance testing and also be randomly assigned to either include, or not include 3TC/FTC in this new regimen. The purpose of the research is to investigate whether the change in therapy results in a decrease in the amount of virus particles and an increase in the CD4 cell count. In addition the researchers are investigating the relationship between the existence of resistance and the rate of decrease in viral load, and also to determine if continuing 3TC/FTC (despite being resistant to the medications) has any effect on the rate of decrease of viral load, or effect on CD4 counts.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• 3TC and FTC

Locations

Country	Name	City	State
United States	Santa Clara Medical Center, PACE Clinic	San Jose	California

Sponsors (3)

Lead Sponsor	Collaborator
Stanford University	Santa Clara Valley Health & Hospital System, University of California, Davis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the role of lamivudine, (3TC), and emtricitabine, (FTC), in salvage regimens in patients with prior 3TC/FTC use, documented resistance to 3TC/FTC, and ongoing viremia as assessed by:
Primary	Impact on the initial rate of change in HIV-1 viral load after removing 3TC/FTC from the failing regimen, and
Primary	Overall change from baseline in HIV-1 viral load at 24 weeks (HIV-VL AUC 24 wks).
Secondary	To evaluate the impact of continued versus discontinued 3TC/FTC on the prevalence, frequency and dynamics of the M184V/I amino acid substitution over 24 weeks.
Secondary	To determine the proportion of patients failing and/or not responding to therapy after 24 weeks as defined by failure to achieve HIV-1 viral load less than 400 copies/ml and/or less than 50 copies/ml
Secondary	To assess the changes from baseline in absolute CD4 (and CD8) cell counts at 24 weeks.