HIV Persistence and Viral Reservoirs

NCT ID: NCT01025427

Last Updated: 2020-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2013-10-31

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.

Conditions

HIV; HIV Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Elite controller

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

Group Type: EXPERIMENTAL

Raltegravir, tenofovir/emtricitabine

Intervention Type: DRUG

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

Interventions

Raltegravir, tenofovir/emtricitabine

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

Intervention Type: DRUG

Eligibility Criteria

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. "Controllers": antiretroviral untreated with 50-1000 copies/mL viral load for at least 12 months

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

California HIV/AIDS Research Program

OTHER

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hiroyu Hatano, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

San Francisco General Hospital

San Francisco, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24130489 (View on PubMed)

Other Identifiers

H52889-35080

Identifier Type: -

Identifier Source: org_study_id