Immune Activation and Drug Absorption in HIV-Infected Patients

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.

Timeline

Start

2014-06

Primary completion

2016-03

Completion

2016-03-14

Publications

• Background 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.
• 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.
• 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.
• 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.

Drugs

Indications