Effects of Intensive cART During Acute/Early HIV Infection

• ClinicalTrials.gov Identifier: NCT01154673
• Recruitment Status: Completed
• First Posted: July 1, 2010
• Results First Posted: April 5, 2016
• Last Update Posted: April 5, 2016
• Sponsor: University of Toronto
• Collaborators: St. Michael's Hospital, Toronto; Maple Leaf Medical Clinic
• Information provided by (Responsible Party): Mario Ostrowski, University of Toronto

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 (Clinical Trial)
• 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: November 2011
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: September 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 Name: 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 Name: 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. [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Ontario

University of Toronto

Toronto, Ontario, Canada, M5B 1W8

Maple Leaf Medical Clinic

Toronto, Ontario, Canada, M5G 1K2

Sponsors and Collaborators

University of Toronto

St. Michael's Hospital, Toronto

Maple Leaf Medical Clinic

Investigators

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

More Information

• Responsible Party: Mario Ostrowski, Principal Investigator, University of Toronto
• ClinicalTrials.gov Identifier: NCT01154673
• Obsolete Identifiers: NCT01101516
• Other Study ID Numbers: 041009
• First Posted: July 1, 2010
• Results First Posted: April 5, 2016
• Last Update Posted: April 5, 2016
• Last Verified: March 2016

Additional relevant MeSH terms:

Infection; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; Ritonavir; Lopinavir; Tenofovir; Emtricitabine; Raltegravir Potassium; Maraviroc; HIV Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Reverse Transcriptase Inhibitors