Immune Responses in Patients Treated With Raltegravir

NCT00785967 | Withdrawn Phase 3

• 2 other identifiers: MK0518-048-00, Version 2.2HC-TPD Control # 120132
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis: Treatment with raltegravir does not alter V(D)J recombination or immune responses to neoantigens. A process known as V(D)J recombination is essential for developing lymphocytes and the specific functioning of the immune system. Raltegravir is the first approved drug of the new integrase inhibitor class of anti-HIV drugs. Integrase inhibitors have been shown in some studies to interfere with DNA cleavage and the activities of RAG-1/2. These studies suggest a potential to affect aspects of both B-cell and T-cell development, therefore, it is important to evaluate the potential effects that integrase inhibitors may have in clinical use. If immunoglobulin and T-cell receptor genes are altered by HIV integrase, then patient lymphocytes will fail to display normal responses to vaccinations.

Conditions

HIV Infections

Keywords

V(D)J recombination; RAG-1/2 recombinase function

Outcome Measures

Primary Outcomes (1)

• Percent of patients with phiX174 IgG greater than or equal to 30% of total anti-phiX174 titers

  Two weeks after fourth phiX174 immunization

Secondary Outcomes (1)

• Total phiX174 antibody titers

  2 and 4 weeks after each immunization

Study Arms (2)

1

EXPERIMENTAL

raltegravir 400mg bid + Truvada 1 tab qd

Biological: Various vaccines

2

ACTIVE COMPARATOR

efavirenz 600mg qhs + Truvada 1 tab qd (or Atripla 1 tab qhs)

Biological: Various vaccines

Interventions

Various vaccines BIOLOGICAL

VAQTA: 1.0ml IM at weeks 24 \& 48; Pneumovax 23: 0.5ml IM at screening; Td ADSORBED: 0.5ml IM at screening; phiX174 bacteriophage: 0.02ml/kg body weight IV at weeks 28, 32, 36, 40.

Also known as: VAQTA;, Pneumovax 23;, Td ADSORBED;, phiX174 bacteriophage

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infected males, as determined by ELISA and Western blot;
• \>18 years of age;
• Current ARV therapy with efavirenz + Truvada® for \>52 weeks;
• HIV-1 RNA (bDNA) \<50 copies/ml for at least 52 weeks;
• No history of hepatitis A vaccine, and HAV antibody negative.

You may not qualify if:

• any immunomodulatory therapy within 24 weeks of screening or during the trial;
• any type of vaccine within 24 weeks of screening or during the trial;
• current opportunistic infection, malignancy, acute infection, or febrile illness;
• history of hypersensitivity to a vaccine, components of a vaccine, or components of a vaccine container.

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Immune Deficiency Treatment Centre, Montreal General Hospital, McGill University Health Centre

Montreal, Quebec, H3G 1A4, Canada

Location

Related Publications (1)

• Melek M, Jones JM, O'Dea MH, Pais G, Burke TR Jr, Pommier Y, Neamati N, Gellert M. Effect of HIV integrase inhibitors on the RAG1/2 recombinase. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):134-7. doi: 10.1073/pnas.012610699. Epub 2001 Dec 26.

  PMID: 11756686 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

Hepatitis A Vaccines; 23-valent pneumococcal capsular polysaccharide vaccine; E protein, bacteriophage X174

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Christos M Tsoukas, MD, FRCPC

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Division of Allergy & CLinical Immunology, MUHC

Study Record Dates

• First Submitted: November 4, 2008
• First Posted: November 5, 2008
• Study Start: January 1, 2009
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: April 14, 2015

Record last verified: 2015-04

Locations

CA (1)