Immune Activation and Drug Absorption in HIV-Infected Patients

NCT01845298 | Completed

• 1 other identifier: TMC114HIV4076
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators' objective is to describe the variability of rifampicin absorption, markers of inflammation and gut damage, intestinal absorptive capacity, and intestinal permeability among HIV-infected volunteers. Rifampicin is the least well absorbed of the first-line anti-tuberculosis drugs. Rifampicin malabsorption is frequently observed in HIV-infected patients with active tuberculosis, but cannot be predicted by patient factors such as CD4+ T cell count, viral load, or the presence of diarrhea. The mechanisms for rifampicin malabsorption in HIV-infected patients are unknown. An understanding of mechanisms for rifampicin malabsorption could eventually lead to new therapeutic targets, with the ultimate goal of improving HIV/tuberculosis treatment outcomes.

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (1)

• Rifampicin Absorption (Ka)

  The investigators will perform a pharmacokinetic study to assess rifampicin absorption among study subjects. Pharmacokinetic modeling will be used to assess the absorption rate constant (Ka) for each subject.

  Baseline

Study Arms (1)

HIV-infected subjects

EXPERIMENTAL

HIV-infected subjects who have not yet initiated highly active antiretroviral therapy (HAART). All enrolled subjects will receive a single dose of rifampicin 600 mg.

Drug: Rifampicin 600 mg

Interventions

Rifampicin 600 mg DRUG

The investigators will administer a single dose of rifampicin 600 mg to study subjects in order to conduct a pharmacokinetic study of rifampicin absorption.

Also known as: rifamycin

HIV-infected subjects

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-infected males and females, between the ages of 21 and 45 years.
• Naïve to antiretroviral therapy
• T cell count greater than 350 cells/mm3
• Body Mass Index (BMI) greater or equal to 19 and less than or equal to 33.
• Weight greater than 60 kilograms.
• Ability and willingness to provide informed consent.
• Ability to swallow oral medications

You may not qualify if:

• Breastfeeding.
• Allergy or sensitivity to rifampicin.
• Prior history of documented active tuberculosis infection.
• Receipt of any investigational therapy, chemotherapy, or immune modulatory agents within 42 days prior to study entry.
• The following laboratory values obtained within 42 days prior to study entry:
• Hemoglobin \< 12.0 g/dL; Females: Hemoglobin \< 11.0 g/dL Platelet count \< 100,000/mm3 AST, ALT, and bilirubin \> 5x ULN An estimated creatinine clearance \< 80 mL/min based on the Cockroft-Gault equation
• Positive blood test for latent tuberculosis infection (T-SPOT)
• Female participants of reproductive potential must have a negative serum or urine pregnancy test performed with 28 days prior to study entry.
• "Female participants of reproductive potential" is defined as women who have reached menarche or who have not been post-menopausal for at least 24 consecutive months (i.e. who have had menses within the preceding 24 months) or who have not undergone surgical sterilization (e.g. hysterectomy, or bilateral oophorectomy or salpingectomy).
• Female participants of reproductive potential that are using oral contraceptive pills (OCPs) must be willing to use barrier precautions for contraception for at least 7 days following each study visit.
• Use of any of the following prescription medications within 30 days prior to study entry, which may have drug-drug interactions with rifampicin, including (but not limited to):
• Anti-coagulants (warfarin)
• Cardiac drugs (digoxin, quinidine, verapamil, nifedipine, metoprolol, atenolol, carvedilol)
• Hypoglycemics (rosiglitazone, pioglitazone, glipizide, repaglinide)
• Proton pump inhibitors (omeprazole, esomeprazole,

Sponsors & Collaborators

• Drexel University: lead

Study Sites (1)

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

Related Publications (4)

• Gurumurthy P, Ramachandran G, Hemanth Kumar AK, Rajasekaran S, Padmapriyadarsini C, Swaminathan S, Bhagavathy S, Venkatesan P, Sekar L, Mahilmaran A, Ravichandran N, Paramesh P. Decreased bioavailability of rifampin and other antituberculosis drugs in patients with advanced human immunodeficiency virus disease. Antimicrob Agents Chemother. 2004 Nov;48(11):4473-5. doi: 10.1128/AAC.48.11.4473-4475.2004.

  PMID: 15504887 BACKGROUND

• Chigutsa E, Visser ME, Swart EC, Denti P, Pushpakom S, Egan D, Holford NH, Smith PJ, Maartens G, Owen A, McIlleron H. The SLCO1B1 rs4149032 polymorphism is highly prevalent in South Africans and is associated with reduced rifampin concentrations: dosing implications. Antimicrob Agents Chemother. 2011 Sep;55(9):4122-7. doi: 10.1128/AAC.01833-10. Epub 2011 Jun 27.

  PMID: 21709081 BACKGROUND

• Sharpstone D, Neild P, Crane R, Taylor C, Hodgson C, Sherwood R, Gazzard B, Bjarnason I. Small intestinal transit, absorption, and permeability in patients with AIDS with and without diarrhoea. Gut. 1999 Jul;45(1):70-6. doi: 10.1136/gut.45.1.70.

  PMID: 10369707 BACKGROUND

• Vinnard C, Manley I, Scott B, Bernui M, Adams J, Varghese S, Zentner I, Kutzler MA. A Pilot Study of Immune Activation and Rifampin Absorption in HIV-Infected Patients without Tuberculosis Infection: A Short Report. Tuberc Res Treat. 2017;2017:2140974. doi: 10.1155/2017/2140974. Epub 2017 Dec 21.

  PMID: 29430306 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Rifampin; rifamycin SV

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)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Christopher Vinnard, MD

  Faculty

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2013
• First Posted: May 3, 2013
• Study Start: June 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 14, 2016
• Last Updated: March 3, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)