Addition of Raltegravir to Established Antiretroviral Suppressive Therapy

NCT ID: NCT01245101

Last Updated: 2016-12-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2013-05-31

Brief Summary

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.

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.

Conditions

HIV

Keywords

HIV raltegravir intensification replication activation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Raltegravir and then Observation

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.

Group Type: EXPERIMENTAL

Raltegravir

Intervention Type: DRUG

Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.

Observation and then Raltegravir

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.

Group Type: ACTIVE_COMPARATOR

Raltegravir

Intervention Type: DRUG

Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.

Interventions

Raltegravir

Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.

Intervention Type: DRUG

Raltegravir

Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

To qualify for this study, participants will need to have:

1. At least 18 years of age

2. Documented HIV-1 infection

3. CD4+ count <350 cells/mm3 at the time of enrollment or CD4+ count increase of <100 cells/mm3 within the past 2 years

4. 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

1. Pregnancy or breast-feeding

2. Prior use of raltegravir at any time in the past

3. Use of any investigational, immunomodulatory, immunosuppressive agents within 90 days prior or during this study

4. Alcohol or substance abuse that in the opinion of the investigator might interfere with patient compliance or safety

5. Any condition or pre-study laboratory abnormality that in the opinion of the investigator might interfere with patient compliance or safety

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Rafael Campo

Professor of Clinical

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rafael E Campo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

Infectious Diseases Research Unit, University of Miami Miller School of Medicine

Miami, Florida, United States

Countries

United States

Other Identifiers

20100499

Identifier Type: -

Identifier Source: org_study_id