Back to results

HIV Persistence and Viral Reservoirs

Primary Purpose

HIV, HIV Infections

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Raltegravir, tenofovir/emtricitabine

About this trial

This is an interventional treatment trial for HIV focused on measuring HIV, HIV persistence, HIV reservoirs

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age ≥18 years, and
HIV infection, and
Antiretroviral-naïve, and
CD4+ T cell count >350 cells/mm3, and
"Controllers": antiretroviral untreated with 50-1000 copies/mL viral load for at least 12 months

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.

Sites / Locations

San Francisco General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Elite controller

Arm Description

Sixteen controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.

Outcomes

Primary Outcome Measures

Mean Change in Estimated Ultrasensitive Plasma HIV RNA Levels Between Baseline and Week 24

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01025427

First Posted

December 1, 2009

Last Updated

June 29, 2020

Sponsor

University of California, San Francisco

Collaborators

California HIV/AIDS Research Program, Gilead Sciences, Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01025427

Brief Title

HIV Persistence and Viral Reservoirs

Official Title

Treating HIV-infected Elite Controllers as a Model of HIV Remission

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

December 2009 (undefined)

Primary Completion Date

November 2012 (Actual)

Study Completion Date

October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, San Francisco

Collaborators

California HIV/AIDS Research Program, Gilead Sciences, Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV, HIV Infections

Keywords

HIV, HIV persistence, HIV reservoirs

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Elite controller

Arm Type

Experimental

Arm Description

Sixteen controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.

Intervention Type

Drug

Intervention Name(s)

Raltegravir, tenofovir/emtricitabine

Intervention Description

16 controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.

Primary Outcome Measure Information:

Title

Mean Change in Estimated Ultrasensitive Plasma HIV RNA Levels Between Baseline and Week 24

Description

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥18 years, and HIV infection, and Antiretroviral-naïve, and CD4+ T cell count >350 cells/mm3, and "Controllers": antiretroviral untreated with 50-1000 copies/mL viral load for at least 12 months 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hiroyu Hatano, MD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

San Francisco General Hospital

City

San Francisco

State/Province

California

ZIP/Postal Code

94110

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24130489

Citation

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.

Results Reference

derived

Learn more about this trial

HIV Persistence and Viral Reservoirs

We'll reach out to this number within 24 hrs