Addition of Raltegravir to Established Antiretroviral Suppressive Therapy
Recruitment status was Not yet recruiting
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Purpose
This study will examine whether intensification with raltegravir of a suppressive antiretroviral regimen in HIV infected patients with poor immune restoration has a beneficial effect on cryptic viral replication and the immune system. Specifically, the investigators will examine the effect that raltegravir intensification of ART has on episomal cDNA frequencies, immune activation, CD4+ cell counts and apoptosis, and markers of microbial translocation.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV |
Drug: Raltegravir |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Prospective, Open-Label, Double-Arm, Crossover, Single-Center Pilot Study to Evaluate the Addition of Raltegravir to Established Suppressive Antiretroviral Therapy While Monitoring Changes in Markers of Immune Activation Among HIV-1 Infected Individuals Without Adequate Immune Restoration |
- Episomal HIV cDNA formation [ Time Frame: 40 weeks ] [ Designated as safety issue: No ]These are linear viral cDNAs that are subsequently circularized by the DNA repair apparatus of the host cell to form episomes. They are markers of ongoing viral replication.
- Markers of immune activation [ Time Frame: 40 weeks ] [ Designated as safety issue: No ]Flow cytometry will be performed in whole blood for analysis of markers CD3, CD4, CD8, HLA-DR and CD38 by standard methodology using a LSR-II flow cytometer. Percentage and absolute counts of CD3+CD4+T cells, and frequencies of CD3+CD8+ subset, CD8+CD38+; CD8+ HLA-DR+ and CD8+HLADR+ CD38+ cells will be determined.
| Estimated Enrollment: | 40 |
| Study Start Date: | January 2011 |
| Estimated Study Completion Date: | June 2012 |
| Estimated Primary Completion Date: | December 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Group A
The total duration of the study will be 40 weeks. This will include Part 1 (16 weeks) followed by Part 2 (8 weeks) followed by the crossover to Part 2 (16 weeks). During Part 1 participants in Group A will receive open-label raltegravir in addition to their established antiretroviral regimen while Group B participants will continue taking their established antiretroviral regimen for 16 weeks. After completion of Part 1, both groups will enter Part 2 that will consist of a washout period of 8 weeks during which both groups will only take their established antiretroviral regimen without raltegravir. This will be followed by Part 3 during which the two study groups will undergo a crossover with respect to the treatment assignment during Part 1 so that Group A will continue to receive their established antiretroviral regimen while Group B will receive open-label raltegravir in addition to their established antiretroviral regimen for 16 weeks.
|
Drug: Raltegravir
Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.
|
|
Active Comparator: Group B
The total duration of the study will be 40 weeks. This will include Part 1 (16 weeks) followed by Part 2 (8 weeks) followed by the crossover to Part 2 (16 weeks). During Part 1 participants in Group A will receive open-label raltegravir in addition to their established antiretroviral regimen while Group B participants will continue taking their established antiretroviral regimen for 16 weeks. After completion of Part 1, both groups will enter Part 2 that will consist of a washout period of 8 weeks during which both groups will only take their established antiretroviral regimen without raltegravir. This will be followed by Part 3 during which the two study groups will undergo a crossover with respect to the treatment assignment during Part 1 so that Group A will continue to receive their established antiretroviral regimen while Group B will receive open-label raltegravir in addition to their established antiretroviral regimen for 16 weeks.
|
Drug: Raltegravir
Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.
|
Detailed Description:
This is a single-center, open-label, double-arm, crossover study which will include approximately 40 HIV-infected subjects on an established suppressive HAART for at least 2 years with evidence of undetectable HIV-1 RNA levels (either <50 copies/ml by RT-PCR or <75 copies/ml by bDNA assay) and CD4+ count of <350 cells/mm3 or an increase in CD4+count <100 cells/mm3 in the last 2 years. Participants (~20 Group 1 and ~20 in Group 2) will be randomly assigned to 1 of the 2 treatment arms described below in Table 1:
Table 1. Study groups and treatment assignments
Group A Raltegravir 400 mg PO q12h in addition to established ART (Part 1) followed by a washout period only on ART (Part 2) followed by ART (Part 3)
Group B Established ART (Part 1) followed by a washout period only on ART (Part 2) followed by raltegravir 400 mg PO q12h in addition to ART (Part 3)
The participants' pre-study HAART will be monitored so as to ensure that the distribution of NNRTI to PI-based regimens is roughly 1:1 and no higher than 2 (NNRTI):1 (PI).
The total duration of the study will be 40 weeks. This will include Part 1 (16 weeks) followed by Part 2 (8 weeks) followed by the crossover to Part 2 (16 weeks) (Figure 1). During Part 1 participants in Group A will receive open-label raltegravir in addition to their established antiretroviral regimen while Group B participants will continue taking their established antiretroviral regimen for 16 weeks. After completion of Part 1, both groups will enter Part 2 that will consist of a washout period of 8 weeks during which both groups will only take their established antiretroviral regimen without raltegravir. This will be followed by Part 3 during which the two study groups will undergo a crossover with respect to the treatment assignment during Part 1 so that Group A will continue to receive their established antiretroviral regimen while Group B will receive open-label raltegravir in addition to their established antiretroviral regimen for 16 weeks.
After obtaining informed consent, patients will be enrolled into the study, a study number will be assigned, a complete history will be obtained, and a physical exam will be performed. Blood will be drawn for the following laboratory exams at Day 1 and at Weeks 1, 2, 4, 10, 16, 24, 25 26, and 40 for Group A and at Day 1 and at Weeks 1, 2, 16, 24, 25, 26, 28, 34, and 40 for Group B:
- T-cell subsets
- Plasma viral load
- Episomal viral cDNA PCR
- HLA-DR levels
- CD38 levels
Blood will also be drawn for the following laboratory exams at Day 1 and at Weeks 4, 12, 16, 24, 28, 36, and 40 for both Group A and Group B to determine
- Plasma levels of LPS, 16s ribosomal DNA, and sCD14
- T cell receptor excision circles
- CD4+ and CD8+ T-cell apoptosis
At all visits, a directed physical exam will be performed on an as-needed-basis.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
To qualify for this study, participants will need to have:
- At least 18 years of age
- Documented HIV-1 infection
- CD4+ count <350 cells/mm3 at the time of enrollment or CD4+ count increase of <100 cells/mm3 within the past 2 years
- Plasma viral load <400 copies/ml at all testing time points within the preceding 2 years AND <50 copies/ml by RT-PCR or <75 copies/ml by bDNA at the 2 testing time points immediately preceding enrollment into the study
Exclusion Criteria:
To qualify for this study, patients must not meet any of the following exclusion criteria:
- Pregnancy or breast-feeding
- Prior use of raltegravir at any time in the past
- Use of any investigational, immunomodulatory, immunosuppressive agents within 90 days prior or during this study
- Alcohol or substance abuse that in the opinion of the investigator might interfere with patient compliance or safety
- Any condition or pre-study laboratory abnormality that in the opinion of the investigator might interfere with patient compliance or safety
Contacts and Locations| Contact: Tom Tanner, RN | 305-243-5621 | |
| Contact: Rafael E Campo, MD | 305-243-3006 |
| United States, Florida | |
| Infectious Diseases Research Unit, University of Miami Miller School of Medicine | Not yet recruiting |
| Miami, Florida, United States, 33136 | |
| Contact: Tom Tanner, RN 305-243-5621 ttanner@med.miami.edu | |
| Principal Investigator: Rafael E Campo, MD | |
| Infectious Diseases Research Unit, University of Miami Miller School of Medicine | Not yet recruiting |
| Miami, Florida, United States, 33136 | |
| Contact: Tom Tanner, RN 305-243-5621 ttanner@med.miami.edu | |
| Principal Investigator: | Rafael E Campo, MD | University of Miami |
More Information
No publications provided
| Responsible Party: | Rafael E. Campo, MD, University of Miami Miller School of Medicine |
| ClinicalTrials.gov Identifier: | NCT01245101 History of Changes |
| Other Study ID Numbers: | UM 20100499 |
| Study First Received: | November 19, 2010 |
| Last Updated: | November 19, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by University of Miami:
|
HIV raltegravir intensification replication activation |
ClinicalTrials.gov processed this record on May 19, 2013