HIV Persistence and Viral Reservoirs
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|ClinicalTrials.gov Identifier: NCT01025427|
Recruitment Status : Completed
First Posted : December 3, 2009
Results First Posted : July 1, 2020
Last Update Posted : July 1, 2020
Although highly active antiretroviral therapy (HAART) decreases HIV-associated mortality, it does not to completely restore health. Patients doing well on otherwise effective HAART remain at risk for cancer, cardiovascular/liver disease, osteopenia, and other "non-AIDS-defining" events. While complete eradication may never be feasible, a "functional cure" in which patients are able to maintain undetectable viral loads indefinitely without therapy may be possible. The best evidence for this are the so-called "elite" controllers, whom we define as individuals who are HIV-seropositive, with plasma HIV RNA levels below the level of conventional detection without treatment. Controllers may be conceptualized as a naturally occurring model of a functional cure (or "HIV remission"), and are ideal patients in which to study HIV persistence and the possibility of eradication.
We propose to conduct a pilot study to better characterize the reservoirs that lead to viral persistence in a group of well-characterized controllers. We propose two specific aims: 1) to characterize the dynamics of viral production in blood and gut-associated lymphoid tissue (GALT) in controllers; and 2) to prospectively treat 10 controllers with raltegravir, tenofovir/emtricitabine for 24 weeks and study the effects of HAART on viral dynamics and host inflammatory responses.
Our primary hypotheses are: 1) viral replication is ongoing in untreated controllers, 2) HAART will reduce viral replication in blood and GALT and decrease immune activation, and 3) higher levels of immune activation are associated with greater measures of microbial translocation and distribution of virus to more differentiated T cell subsets.
|Condition or disease||Intervention/treatment||Phase|
|HIV HIV Infections||Drug: Raltegravir, tenofovir/emtricitabine||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Treating HIV-infected Elite Controllers as a Model of HIV Remission|
|Study Start Date :||December 2009|
|Actual Primary Completion Date :||November 2012|
|Actual Study Completion Date :||October 2013|
Experimental: Elite controller
Sixteen controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.
Drug: Raltegravir, tenofovir/emtricitabine
16 controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.
- Mean Change in Estimated Ultrasensitive Plasma HIV RNA Levels Between Baseline and Week 24 [ Time Frame: 24 weeks ]The isothermal transcription mediated amplification (TMA) assay (Aptima, Gen-Probe/Hologic) was used to measure ultrasensitive plasma HIV RNA levels at weeks 0, 4, 12, and 24. This is a nucleic acid-amplification test that has been FDA-approved for the early detection of HIV infection in blood donors. It is a highly specific and sensitive assay, with a singlicate 50% detection limit of 3.6-14 copies/mL. The assay was performed in triplicate on 0.5 mL plasma (1.5 mL total plasma), improving the overall 50% detection limit to < 5 copies/mL.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01025427
|United States, California|
|San Francisco General Hospital|
|San Francisco, California, United States, 94110|
|Principal Investigator:||Hiroyu Hatano, MD||University of California, San Francisco|