Effects of Intensive cART During Acute/Early HIV Infection

• Sponsor: University of Toronto (Other)
• Overall Status: Completed
• CT.gov ID: NCT01154673
• Collaborator: Unity Health Toronto (Other), Maple Leaf Medical Clinic (Other)
• Enrollment: 32
• Locations: 2
• Arms: 2
• Duration (Months): 34
• Patients Per Site: 16
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute HIV Infection	Drug: raltegravir; Drug: maraviroc; Drug: emtricitabine 200mg /tenofovir 300mg; Drug: lopinavir 400 mg/ritonavir 100mg	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-blinded, Controlled Trial of Intensive HAART Including Raltegravir, and Maraviroc, on HIV-1 Pro-viral DNA and Reservoir Decay in HIV-1-infected Individuals During the Acute/Early Infection
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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 for 96 weeks	Drug: raltegravir; Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART; Other Names: Isentress MK-0518 ; Drug: maraviroc; Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART; Other Names: Celsentri Selzentry ; Drug: emtricitabine 200mg /tenofovir 300mg; emtricitabine 200mg /tenofovir 300mg QD; Other Names: Truvada ; Drug: lopinavir 400 mg/ritonavir 100mg; lopinavir 400 mg/ritonavir 100mg BID; Other Names: Kaletra Aluvia
Placebo Comparator: 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) for 48 weeks and then offered open label Raltegravir and Maraviroc after 48 weeks	Drug: emtricitabine 200mg /tenofovir 300mg; emtricitabine 200mg /tenofovir 300mg QD; Other Names: Truvada ; Drug: lopinavir 400 mg/ritonavir 100mg; lopinavir 400 mg/ritonavir 100mg BID; Other Names: Kaletra Aluvia

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

1. Participant with a malignancy

2. Participant with other significant underlying disease (non-HIV-1) that might impinge upon disease progression or death

3. Participant who is pregnant or who is trying to conceive

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Toronto	Toronto	Ontario	Canada	M5B 1W8
2	Maple Leaf Medical Clinic	Toronto	Ontario	Canada	M5G 1K2

Sponsors and Collaborators

• University of Toronto
• Unity Health Toronto
• Maple Leaf Medical Clinic

Investigators

• Principal Investigator: Mario Ostrowski, MD, University of Toronto
• Principal Investigator: Colin Kovacs, MD, Maple Leaf Medical Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mario Ostrowski, Principal Investigator, University of Toronto
• ClinicalTrials.gov Identifier: NCT01154673
• Other Study ID Numbers: 041009; NCT01101516
• First Posted: Jul 1, 2010
• Last Update Posted: Apr 5, 2016
• Last Verified: Mar 1, 2016

• Additional relevant MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Ritonavir; Lopinavir; Tenofovir; Emtricitabine; Raltegravir Potassium; Maraviroc

Study Results

Participant Flow

Arm/Group Title	Intensive HAART	Placebo Arm
Arm/Group Description	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 and endpoint is measured at 48 weeks	Placebo (in place of raltegravir and maraviroc) will be added to standard HAART (Emtricitabine 200mg /tenofovir 300mg QD + Lopinavir 400 mg/ritonavir 100mg BID) and endpoint is measured at 48 weeks
Period Title: Overall Study
STARTED	16	16
COMPLETED	14	16
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Intensive HAART	Placebo Arm	Total
Arm/Group Description	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	Placebo (in place of raltegravir and maraviroc) will be added to standard HAART (Emtricitabine 200mg /tenofovir 300mg QD + Lopinavir 400 mg/ritonavir 100mg BID)	Total of all reporting groups
Overall Participants	16	16	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 100%	16 100%	32 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	34	30	32
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	16 100%	16 100%	32 100%
Region of Enrollment (participants) [Number]
Canada	16 100%	16 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intensive HAART	Placebo Arm
Arm/Group Description	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	Placebo (in place of raltegravir and maraviroc) will be added to standard HAART (Emtricitabine 200mg /tenofovir 300mg QD + Lopinavir 400 mg/ritonavir 100mg BID)
Measure Participants	14	16
Median (Full Range) [HIV DNA copies/ million CD4 cells]	279	244

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive HAART, Placebo Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.056
	Comments	"The estimated difference in mean change from baseline to 48 weeks was calculated as the log DNA copies/106 CD4+ T cells in "Intensive HAART" minus the log DNA copies/106 CD4+ T cells in "Placebo Arm"
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -.006 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated difference in mean change from baseline to 48 weeks was calculated as the log DNA copies/106 CD4+ T cells in "Intensive HAART" minus the log DNA copies/106 CD4+ T cells in "Placebo Arm"

Adverse Events

Time Frame	2 years
Arm/Group Title	Intensive HAART		Placebo Arm
Arm/Group Description	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		Placebo (in place of raltegravir and maraviroc) will be added to standard HAART (Emtricitabine 200mg /tenofovir 300mg QD + Lopinavir 400 mg/ritonavir 100mg BID)
All Cause Mortality
	Intensive HAART		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Intensive HAART		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		0/16 (0%)
Blood and lymphatic system disorders
Neutropenia	1/16 (6.3%)	1	0/16 (0%)	0
Other (Not Including Serious) Adverse Events
	Intensive HAART		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.