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HIV Persistence and Viral Reservoirs

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ClinicalTrials.gov Identifier: NCT01025427
Recruitment Status : Unknown
Verified April 2012 by University of California, San Francisco.
Recruitment status was:  Active, not recruiting
First Posted : December 3, 2009
Last Update Posted : April 3, 2012
Information provided by (Responsible Party):

December 1, 2009
December 3, 2009
April 3, 2012
December 2009
June 2011   (Final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01025427 on ClinicalTrials.gov Archive Site
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HIV Persistence and Viral Reservoirs
Treating HIV-infected Elite Controllers as a Model of HIV Remission

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.

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Phase 4
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • HIV
  • HIV Infections
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: Elite controller
    Ten elite controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.
    Intervention: Drug: Raltegravir, tenofovir/emtricitabine
  • Active Comparator: Non-controller
    Ten untreated non-controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.
    Intervention: Drug: Raltegravir, tenofovir/emtricitabine
Hatano H, Yukl SA, Ferre AL, Graf EH, Somsouk M, Sinclair E, Abdel-Mohsen M, Liegler T, Harvill K, Hoh R, Palmer S, Bacchetti P, Hunt PW, Martin JN, McCune JM, Tracy RP, Busch MP, O'Doherty U, Shacklett BL, Wong JK, Deeks SG. Prospective antiretroviral treatment of asymptomatic, HIV-1 infected controllers. PLoS Pathog. 2013;9(10):e1003691. doi: 10.1371/journal.ppat.1003691. Epub 2013 Oct 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Unknown status
June 2013
June 2011   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age ≥18 years, and
  2. HIV infection, and
  3. Antiretroviral-naïve, and
  4. CD4+ T cell count >350 cells/mm3, and
  5. 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:

  1. Persons with known rheumatologic conditions (e.g., systemic lupus erythematosus), because of their predilection for biologic false-positive testing on HIV antibody tests.
  2. 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.
  3. Screening genotype resistance testing showing resistance to tenofovir or emtricitabine.
  4. Known kidney disease.
  5. Known bone disease, including pathologic fractures.
  6. Patients with chronic Hepatitis B infection, because of the risk of liver abnormalities after starting and stopping tenofovir/emtricitabine.
  7. Concurrent treatment with lamivudine, adefovir, entecavir, or telbivudine.
  8. Serious illness requiring hospitalization or parental antibiotics within the preceding 3 months.
  9. 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.
  10. 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.
  11. Concurrent treatment with phenobarbital, phenytoin, or rifampin.
  12. 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.
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
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University of California, San Francisco
University of California, San Francisco
  • California HIV/AIDS Research Program
  • Gilead Sciences
  • Merck Sharp & Dohme Corp.
Principal Investigator: Hiroyu Hatano, MD University of California, San Francisco
University of California, San Francisco
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP