Acute HIV Infection
Conditions
Brief summary
This trial will investigate the efficacy and safety of intensified antiretroviral treatment that includes raltegravir and maraviroc during the early stages of HIV infection. With the proven efficacy of these antiviral drugs in pre- and post-clinical trials, we would like to investigate the ability of the combination of raltegravir and maraviroc plus a standard HAART backbone to further decrease the viral load in acutely infected treated HIV infected individuals.
Detailed description
The trial is a prospective, randomized, double-blinded, placebo-controlled study with follow-up to 5 years. Thirty-two individuals presenting with newly diagnosed acute or early HIV-1 infection as described in the inclusion criteria will be enrolled, with sixteen randomized to each arm. Individuals will be randomized to one of two arms: the Intensive arm with standard HAART (Emtricitabine 200mg /tenofovir 300mg QD + Lopinavir 400mg /ritonavir 100mg BID) + Raltegravir + Maraviroc or the placebo arm with standard HAART+ Placebo for 48 weeks. Another group of individuals diagnosed with acute or early HIV-1 who elect to forego early treatment will be followed as non-randomized, untreated controls. At week 48, all patients will be informed of study results. If results are positive in the intensive treatment group, the placebo group will be offered to roll-over to the intense treatment arm and followed as an open-label cohort out to five years. Participants may stop treatment at any time and withdraw from the study. If they choose to do so, they will be followed according to the standards employed for all HIV-1 patients at the Maple Leaf clinic. At the five year point, the decision to terminate treatment will be made based on the existing state of the HIV-1 literature at the time.
Interventions
DRUGraltegravir
Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART
DRUGmaraviroc
Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART
DRUGemtricitabine 200mg /tenofovir 300mg
emtricitabine 200mg /tenofovir 300mg QD
DRUGlopinavir 400 mg/ritonavir 100mg
lopinavir 400 mg/ritonavir 100mg BID
Sponsors
Unity Health Toronto
Maple Leaf Research
University of Toronto
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 65 Years
Healthy volunteers
No
Inclusion criteria
The major single criterion for inclusion into the study will be the presence of confirmed acute/early HIV-1 infection, as defined by one of the three following criteria: 1. Positive HIV-1 antibody test result (Western blot), with a documented negative test result in the previous six months or 2. Positive or weakly positive HIV-1 antibody screening ELISA test result, with indeterminate and evolving confirmatory test result with demonstrated HIV-1 antigenemia (p24 antigen test result) or viremia (HIV-1 bDNA ≥ 500 copies/ml) or 3. Negative HIV-1 antibody test result in the setting of an illness compatible with acute seroconversion with demonstrated HIV-1 antigenemia (p24 antigen test result) or plasma viremia (HIV-1 bDNA ≥ 500 copies/ml) Other inclusion criteria are: * Ages 18 or older * Ability to provide informed consent * HIV-1 viral load ≥ 5,000 copies/ml
Exclusion criteria
1. Participants who would have difficulty participating in a trial due to non-adherence or substance abuse 2. Participants with any of the following abnormal laboratory test results in screening: * Hemoglobin \< 85 g/L * Neutrophil count \< 750 cells/uL * Platelet count \< 50,000 cells/L * AST or ALT \> 5X the upper limit of normal * Creatinine \> 250 umol/L 3. Participant with a malignancy 4. Participant with other significant underlying disease (non-HIV-1) that might impinge upon disease progression or death 5. Participant who is pregnant or who is trying to conceive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Proviral HIV-1 DNA in Total CD4+ T-cells From Baseline to Week 48 in Participants Randomized to the Intensified Arm Versus the Control Arm Who Received Placebo in Addition to Standard HAART. | Baseline to Week 48 | The level of HIV Provirus in CD4 T cells obtained from peripheral blood at 48 weeks compared to baseline. A quantitative HIV PCR assay was done. The mean/median values from the standard HAART group is compared to the intensive HAART treatment regimen. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intensive HAART Patients in this arm will receive the following HAART regimen:
Raltegravir 400 mg BID + Maraviroc 150mg BID + emtricitabine 200mg /tenofovir 300mg QD + lopinavir 400 mg/ritonavir 100mg BID | 16 |
| Placebo Arm Placebo (in place of raltegravir and maraviroc) will be added to standard HAART (Emtricitabine 200mg /tenofovir 300mg QD + Lopinavir 400 mg/ritonavir 100mg BID) | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | moved out of province | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Arm | Intensive HAART | 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 | 16 Participants | 16 Participants | 32 Participants |
| Age, Continuous | 30 years | 34 years | 32 years |
| Region of Enrollment Canada | 16 participants | 16 participants | 32 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 16 |
| serious Total, serious adverse events | 1 / 16 | 0 / 16 |
Outcome results
Primary
Change in Proviral HIV-1 DNA in Total CD4+ T-cells From Baseline to Week 48 in Participants Randomized to the Intensified Arm Versus the Control Arm Who Received Placebo in Addition to Standard HAART.
The level of HIV Provirus in CD4 T cells obtained from peripheral blood at 48 weeks compared to baseline. A quantitative HIV PCR assay was done. The mean/median values from the standard HAART group is compared to the intensive HAART treatment regimen.
Time frame: Baseline to Week 48
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intensive HAART | Change in Proviral HIV-1 DNA in Total CD4+ T-cells From Baseline to Week 48 in Participants Randomized to the Intensified Arm Versus the Control Arm Who Received Placebo in Addition to Standard HAART. | 279 HIV DNA copies/ million CD4 cells |
| Placebo Arm | Change in Proviral HIV-1 DNA in Total CD4+ T-cells From Baseline to Week 48 in Participants Randomized to the Intensified Arm Versus the Control Arm Who Received Placebo in Addition to Standard HAART. | 244 HIV DNA copies/ million CD4 cells |
p-value: 0.05695% CI: [-0.006, 0.4]Regression, Linear