HIVPhase 4NCT01025427
HIV Persistence and Viral Reservoirs
A Phase 4 study testing Raltegravir, tenofovir/emtricitabine in people with HIV and HIV Infections, run by University of California, San Francisco at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV, HIV Infections
- What is being tested?
- Raltegravir, tenofovir/emtricitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Oct 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
San Francisco General Hospital
San Francisco, California, 94110
About this study
Official title: 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.
- Conditions
- HIV, HIV Infections
- Being tested
- Raltegravir, tenofovir/emtricitabine
- Keywords
- HIV, HIV persistence, HIV reservoirs
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Raltegravir, tenofovir/emtricitabineDrug
16 controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Elite controller | Experimental | Sixteen controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks. Receives: Drug: Raltegravir, tenofovir/emtricitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2009 (estimated)
- Study startDec 2009
- Primary completionNov 2012
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- California HIV/AIDS Research Program, Gilead Sciences, Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Hiroyu Hatano, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01025427
- Sponsor's protocol ID
- H52889-35080
- Status last verified
- Jun 2020
- First submitted
- 1 Dec 2009
- Last updated
- 1 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 24130489
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treating HIV-infected Elite Controllers as a Model of HIV Remission
- ClinicalTrials.gov ID
- NCT01025427
- Acronym / sponsor ID
- H52889-35080
- Conditions
- HIV, HIV Infections
- Keywords
- HIV, HIV persistence, HIV reservoirs
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- California HIV/AIDS Research Program, Gilead Sciences, Merck Sharp & Dohme LLC
- Study start
- Dec 2009
- Primary completion
- Nov 2012 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 3 Dec 2009 (estimated)
- Results
- Posted 1 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Elite controller | Experimental | Drug: Raltegravir, tenofovir/emtricitabineSixteen controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Raltegravir, tenofovir/emtricitabine16 controllers will be treated with open-label raltegravir/tenofovir/emtricitabine for 24 weeks. | Drug | Elite controller |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24130489Hatano 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.
Related trials for HIV
RecruitingPhase 2
Evaluating the Safety and Immunogenicity of MTBVAC
HIV I Infection, Tuberculosis
Active, not recruiting
Evaluating the Effectiveness of a Mobile HIV Prevention App to Increase HIV and Sexually Transmitted Infections (STI) Testing and PrEP Initiation Among Rural Men Who Have Sex With Men
HIV Infections, STI
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Not yet recruiting
PNF RCT to Decrease Alcohol Use and Increase HIV Prevention
HIV (Human Immunodeficiency Virus), Alcohol Misuse
RecruitingObservational study
Studies of the Pathogenesis of HIV Infection in Human Peripheral Blood Cells and/or Body Fluids in People Living With and Without HIV
HIV, Immunodeficiencies
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hiroyu Hatano, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Raltegravir, tenofovir/emtricitabine in people with HIV and HIV Infections, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change in Estimated Ultrasensitive Plasma HIV RNA Levels Between Baseline and Week 24 (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01025427, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2020; AzTrials last refreshed its copy on 2 Nov 2026.