Effect of an Enfuvirtide-based Anti-HIV Drug Regimen on Latent HIV Reservoirs in Treatment Naive Adults
- Conditions
- HIV Infections
- Interventions
- Registration Number
- NCT00051831
- Brief Summary
HIV replication in resting CD4 cells is so minimal that anti-HIV drugs often fail to destroy the virus in these cells. Enfuvirtide, also known as T-20, is a type of anti-HIV drug called a fusion inhibitor. The purpose of this study is to test the ability of a T-20-enhanced treatment regimen to decrease the number of resting CD4 cells that become infected with HIV.
- Detailed Description
While current HIV treatment with combination antiretroviral therapy (ART) has reduced morbidity and mortality, it does not eradicate or cure HIV infection. A possible explanation for this failure is the persistence of virus in long-lived reservoirs. Resting memory CD4 cells have been proposed as providing a cellular reservoir. Most patients who initiate ART during chronic HIV-1 infection do not experience a detectable reduction in HIV in the latent reservoir; this may be due to low levels of ongoing viral replication that maintains the resting CD4 cell reservoir. Increasing the potency of therapy by inhibiting new viral targets may result in a decrease in the number of latently infected cells and clearance of the latent reservoir. Addition of the fusion inhibitor T-20 to ART including reverse transcriptase inhibitors and protease inhibitors (PIs) may help achieve this goal. This study will evaluate whether treatment naive, chronically infected HIV patients treated with T-20 plus emtricitabine (FTC), ritonavir (RTV), saquinavir (SQV), and tenofovir disoproxil fumarate (TDF) have a measurable decline in the latently infected CD4 cell reservoir. Patients and their physicians may choose different PIs than RTV and SQV, but they will not be provided by the study.
Patients in this study will receive injections of T-20 twice daily in addition to oral FTC and TDF once daily and oral RTV and SQV twice daily. At Week 24, patients will have their latent cell reservoir sampled. Patients whose HIV viral loads are less than 50 copies/ml at or after Week 24 but prior to Week 48 will continue the treatment regimen through the end of the study; their latent cell reservoirs will be tested at Weeks 48, 72, and 96. Patients whose viral loads are between 50 copies/ml and 200 copies/ml will continue the treatment regimen and latent cell sampling, but their regimens may be intensified as determined by the study team. Patients whose viral loads are 200 copies/ml or greater after Week 24 may continue their study regimens, but will no longer contribute latent cell samples.
This study will last 96 weeks. During the first 4 months of the study, patients will have 7 study visits; after that, study visits will be every 8 weeks until the end of the study. Medical history, clinical assessments, and blood collection will occur at every study visit. Pill and ENF vial counts will be assessed, and patients will be asked to complete a medication adherence questionnaire at selected study visits.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 Emtricitabine - 1 Saquinavir - 1 Enfuvirtide - 1 Ritonavir - 1 Tenofovir disoproxil fumarate -
- Primary Outcome Measures
Name Time Method Frequency of latently infected CD4+ T cells from peripheral blood with replication-competent HIV-1 (in infectious units per million cells) Throughout study
- Secondary Outcome Measures
Name Time Method - Level of HIV-1 DNA in PBMC Throughout study -CD8/CD38 antibody binding capacity (ABC) Throughout study - Level of HIV-1 RNA in cerebrospinal fluid Throughout study Targeted events and toxicities will also be considered and these include injection site reactions (any grade), bacterial pneumonia, cellulitis Throughout study - Level of HIV-1 RNA in genital fluid Throughout study - Responses to subject preferences and injection administration concerns questionnaires Throughout study - Level of HIV-1 RNA in plasma as measured by the Roche Ultrasensitive assay Throughout study - Frequency of 2-LTR in PBMC Throughout study - Level of HIV-1 RNA in plasma as measured by an ultra-ultrasensitive assay Throughout study - Measures of cell surface density of chemokine (CCR5, CXCR5) receptors Throughout study Any Grade 3 or 4 adverse experience, including Grade 3 or 4 laboratory value, sign or symptom, and all deaths. Throughout study -Sequence of HIV env and HIV pol genes Throughout study
Trial Locations
- Locations (7)
University of Colorado Hospital CRS
🇺🇸Aurora, Colorado, United States
Massachusetts General Hospital ACTG CRS
🇺🇸Boston, Massachusetts, United States
Washington U CRS
🇺🇸Saint Louis, Missouri, United States
NY Univ. HIV/AIDS CRS
🇺🇸New York, New York, United States
Unc Aids Crs
🇺🇸Chapel Hill, North Carolina, United States
Puerto Rico-AIDS CRS
🇵🇷San Juan, Puerto Rico
The Ohio State Univ. AIDS CRS
🇺🇸Columbus, Ohio, United States