HIV Infections
Conditions
Keywords
HIV, Treatment intensification, Low level viremia, Suboptimal CD4+ T cell response, treatment experienced
Brief summary
The purpose of this study is to determine whether treatment with Raltegravir further decreases HIV viral replication in HAART-suppressed, HIV-infected patients, potentially improving immune response to antiretroviral therapy.
Interventions
DRUGRaltegravir
For subjects assigned to the raltegravir group, subjects will receive raltegravir 400 mg to be taken by mouth twice daily, in addition to continuing to take their current anti-HIV medicines.
DRUGPlacebo
For subjects assigned to the placebo group, subjects will receive a matching placebo pill 400 mg to be taken by mouth twice daily for 24 weeks, in addition to continuing to take their current anti-HIV medicines.
Sponsors
Merck Sharp & Dohme LLC
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stable antiretroviral therapy for at least 12 months * Screening CD4+ T cell count \< 350 cells/mm3 * All available CD4+ T cell counts in the last year and at screening \< 350 cells/mm3 * Screening plasma HIV RNA levels below level of detection (\< 50 copies RNA/mL using Roche Amplicor or \< 75 copies/mL using Bayer bDNA or \< 40 copies/mL using Abbott RT-PCR), and all available determinations in past 12 months also below level of detection (isolated single values \> 75 but \< 1000 copies/mL will be allowed if they were preceded and followed by undetectable viral load determinations). * \>90% adherence to therapy within the preceding 30 days, as determined by self-report * Both male and female adult (at least 18 years old) subjects are eligible. 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.
Exclusion criteria
* Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason * Serious illness requiring hospitalization or parental antibiotics within preceding 3 months * \*\*Any vaccination 2 weeks prior to baseline (day 0) visit and throughout the study period * Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drug in past 16 weeks * Concurrent treatment with phenobarbital, phenytoin, or rifampin. * Screening absolute neutrophil count \<1,000 cells/mm3, platelet count \<70,000 cells/mm3, hemoglobin \< 8 mg/dL, estimated creatinine clearance \<40 mL/minute * Pregnant or breastfeeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants in Each Group (Study Drug vs. Placebo) With Undetectable Plasma HIV-1 RNA, as Measured by an Ultra-sensitive Assay With a Limit of Detection of 1 Copy/mL at Week 12. | Week 12 |
Secondary
| Measure | Time frame |
|---|---|
| Change in Percentage of Activated CD8+ T Cells (CD8+ T Cells That Co-express CD38 and HLA-DR) From Baseline to Week 24 | Baseline and Week 24 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Raltegravir For subjects assigned to the raltegravir group, subjects will receive raltegravir 400 mg to be taken by mouth twice daily for 24 weeks, in addition to continuing to take their current anti-HIV medicines. | 15 |
| Placebo For subjects assigned to the placebo group, subjects will receive a matching placebo pill 400 mg to be taken by mouth twice daily for 24 weeks, in addition to continuing to take their current anti-HIV medicines. | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Placebo | Raltegravir | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 30 Participants |
| Age, Continuous | 51.2 years STANDARD_DEVIATION 8 | 50.7 years STANDARD_DEVIATION 10.3 | 51.0 years STANDARD_DEVIATION 9.1 |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 15 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Number of Participants in Each Group (Study Drug vs. Placebo) With Undetectable Plasma HIV-1 RNA, as Measured by an Ultra-sensitive Assay With a Limit of Detection of 1 Copy/mL at Week 12.
Time frame: Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir | Number of Participants in Each Group (Study Drug vs. Placebo) With Undetectable Plasma HIV-1 RNA, as Measured by an Ultra-sensitive Assay With a Limit of Detection of 1 Copy/mL at Week 12. | 11 participants |
| Placebo | Number of Participants in Each Group (Study Drug vs. Placebo) With Undetectable Plasma HIV-1 RNA, as Measured by an Ultra-sensitive Assay With a Limit of Detection of 1 Copy/mL at Week 12. | 8 participants |
Secondary
Change in Percentage of Activated CD8+ T Cells (CD8+ T Cells That Co-express CD38 and HLA-DR) From Baseline to Week 24
Time frame: Baseline and Week 24
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Raltegravir | Change in Percentage of Activated CD8+ T Cells (CD8+ T Cells That Co-express CD38 and HLA-DR) From Baseline to Week 24 | -1.1 Percentage of Activated CD8+ T cells |
| Placebo | Change in Percentage of Activated CD8+ T Cells (CD8+ T Cells That Co-express CD38 and HLA-DR) From Baseline to Week 24 | -0.9 Percentage of Activated CD8+ T cells |