Maraviroc Intensification and Peripheral Blood Monocyte HIV DNA Levels

HIV Infections Clinical Trial

Official title:

Pilot Study of the Effect of Maraviroc Intensification on Peripheral Blood Monocyte HIV DNA Levels When Given to HIV-Infected Subjects Stable on Highly Active Antiretroviral Therapy With Undetectable Plasma HIV RNA

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00987948
• Other study ID #: H005
• Status: Active, not recruiting
• Phase: Phase 2
• First received: September 29, 2009
• Last updated: June 14, 2012
• Start date: January 2010
• Est. completion date: March 2013

Study information

• Verified date: June 2012
• Source: University of Hawaii
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

High levels of HIV infection within blood monocyte/macrophages (a type of white cells in the bloodstream) increases risk of dementia in HIV-infected individuals. Maraviroc (Selzentry) is a HIV medication that works by blocking the entry of HIV in cells including monocytes/macrophages that use a receptor called CCR5. The study hypothesis is that the addition of Maraviroc to a HIV antiretroviral regimen in HIV-infected individuals with high levels of HIV-infected monocyte/macrophages will lead to a decrease in the levels of infected monocyte/macrophages and to decrease in brain inflammation as studied by magnetic resonance spectroscopy (MRS, a form of MRI study).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: March 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV-1 infection as documented by ELISA and confirmed by either Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA by RT-PCR or bDNA at any time prior to study entry.

• Receipt of ARV medication uninterrupted for > 1 year leading up to the screening period with demonstrated HIV RNA < 50 copies/ml for a period of 1 year."

• Willingness for both males and females of childbearing potential to utilize 2 effective contraception methods (2 separate forms, one of which must be an effective barrier method), be non-heterosexually active or have a an exclusive vasectomized partner from screening throughout the duration of the study treatment and for 30 days following the last dose of study drugs.

• Age >18 years.

• Ability and willingness to provide written informed consent

• The following laboratory parameters documented within 30 days prior to study entry:

• Hemoglobin >8.0

• Absolute neutrophil count >500

• Platelet count >40,000

• AST (SGOT) and ALT (SGPT) <5 x ULN

• Creatinine <1.5 x ULN

• Lipase <2.0 x ULN

• Estimated creatinine clearance > 60 mL/min.

• HIV DNA within peripheral blood mononuclear cells > 100 copies/mL

• Not currently receiving Maraviroc as part of ARV regimen

Exclusion Criteria:

• Past or present HIV opportunistic infection of the brain, learning disability, head injury with prolonged loss of consciousness or cognitive sequelae, or other non-HIV risk factor that may impact cognitive performance.

• Any factor that precludes MRI scan including presence of metal or exposure to metal work (e.g., metal grinder/worker) and claustrophobia

• History of seizure disorder

• History of myocardial infarction, angina, congestive heart failure, peripheral vascular disease, angioplasty or cardiac surgery

• Current malignancy or history of past malignancies excluding basal cell CA

• Any immunomodulator, HIV vaccine, or investigational therapy within 30 days of study entry.

• Any vaccination within 30 days of study entry.

• Requirement for acute therapy for other AIDS-defining illness or other serious medical illnesses (in the opinion of the site investigator) within 14 days prior to study entry.

• Other chronic illnesses including diabetes, autoimmune diseases, and endocrinopathies, except subjects on stable physiologic replacement therapy for low testosterone or thyroid levels

• Known hypersensitivity to Maraviroc

• Any condition which, in the opinion of the investigator, would compromise the subject's ability to participate in the study

• Current active substance or alcohol dependence

• Pregnancy or breast-feeding, intent to become pregnant during the course of the study.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• maraviroc (Selzentry)
dosage varies with other medications being taken; will follow package insert guidelines

Locations

Country	Name	City	State
United States	Hawaii Center for AIDS	Honolulu	Hawaii

Sponsors (2)

Lead Sponsor	Collaborator
University of Hawaii	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in peripheral blood monocyte HIV DNA (HIV DNA within CD14+ PBMCs)		week 24 of study	No
Secondary	Safety and tolerability of intensification with maraviroc		24 weeks	Yes
Secondary	Change in HIV DNA overall in PBMCs and in CD14- cells		24 weeks	No
Secondary	Change in plasma HIV RNA and CD4 count		24 weeks	No
Secondary	Change in neuropsychological testing parameters		24 weeks	No