HIV Persistence and Viral Reservoirs - Full Text View

Sponsor:	University of California, San Francisco
Collaborators:	California HIV/AIDS Research Program Gilead Sciences Merck
Information provided by (Responsible Party):	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT01025427

Purpose

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	Intervention	Phase
HIV HIV Infections	Drug: Raltegravir, tenofovir/emtricitabine	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Treating HIV-infected Elite Controllers as a Model of HIV Remission

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Emtricitabine Tenofovir Tenofovir Disoproxil Fumarate Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:

Change in proportion of controllers with detectable plasma HIV RNA (using an ultrasensitive <1 copy/mL assay) from baseline to Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	December 2009
Estimated Study Completion Date:	June 2013
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Elite controller Ten elite controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.	Drug: Raltegravir, tenofovir/emtricitabine Ten elite controllers and 10 untreated non-controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.
Active Comparator: Non-controller Ten untreated non-controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.	Drug: Raltegravir, tenofovir/emtricitabine Ten elite controllers and 10 untreated non-controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age ≥18 years, and
HIV infection, and
Antiretroviral-naïve, and
CD4+ T cell count >350 cells/mm3, and
Meeting one of the following criteria:

1. "Elite controllers": antiretroviral untreated with an undetectable (< 50 copies/mL) viral load for at least 12 months (isolated blips up to 1,000 copies/mL allowed, but must be preceded and followed by undetectable viral load), or 2. "Non-controllers": antiretroviral untreated with a detectable (> 10,000 copies/mL) viral load, with the intent to start antiretroviral drugs.

Exclusion criteria:

Persons with known rheumatologic conditions (e.g., systemic lupus erythematosus), because of their predilection for biologic false-positive testing on HIV antibody tests.
Screening absolute neutrophil count <1,000 cells/mm3, platelet count <70,000 cells/mm3, hemoglobin < 8 mg/dL, estimated creatinine clearance <40 mL/minute, aspartate aminotransferase >100 units/L, alanine aminotransferase >100 units/L.
Screening genotype resistance testing showing resistance to tenofovir or emtricitabine.
Known kidney disease.
Known bone disease, including pathologic fractures.
Patients with chronic Hepatitis B infection, because of the risk of liver abnormalities after starting and stopping tenofovir/emtricitabine.
Concurrent treatment with lamivudine, adefovir, entecavir, or telbivudine.
Serious illness requiring hospitalization or parental antibiotics within the preceding 3 months.
Any vaccination 2 weeks prior to baseline (Day 0) visit and throughout the study period. NOTE: Because the study will most likely be actively recruiting during the influenza season, all subjects will be encouraged to receive their annual influenza vaccine at the screening visit (4 weeks prior to baseline [Day 0] visit) if they have not already been vaccinated for the 2009-10 season and if it is medically indicated.
Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drug in the preceding 16 weeks (e.g. corticosteroid therapy equal to or exceeding a dose of 15 mg/day of prednisone for more than 10 days, IL-2, interferon-alpha, methotrexate, cancer chemotherapy). NOTE: Use of inhaled or nasal steroid use is not exclusionary.
Concurrent treatment with phenobarbital, phenytoin, or rifampin.
Pregnant or breastfeeding women. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01025427

Locations

United States, California
San Francisco General Hospital
San Francisco, California, United States, 94110

Sponsors and Collaborators

University of California, San Francisco

California HIV/AIDS Research Program

Gilead Sciences

Merck

Investigators

Principal Investigator:

Hiroyu Hatano, MD

University of California, San Francisco

More Information

No publications provided

Responsible Party:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT01025427 History of Changes
Other Study ID Numbers:	H52889-35080
Study First Received:	December 1, 2009
Last Updated:	April 2, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, San Francisco:

HIV
HIV persistence
HIV reservoirs

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir

Tenofovir disoproxil
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 23, 2012