Abstract
We previously characterized a human betaretrovirus and linked infection with the development of primary biliary cholangitis (PBC). There are in vitro and in vivo data demonstrating that antiretroviral therapy used to treat human immunodeficiency virus (HIV) can be repurposed to treat betaretroviruses. As such, PBC patients have been treated with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), alone and in combination with a boosted protease inhibitor or an integrase strand transfer inhibitor in case studies and clinical trials. However, a randomized controlled trial using combination antiretroviral therapy with lopinavir was terminated early because 70% of PBC patients discontinued therapy because of gastrointestinal side effects. In the open-label extension, patients tolerating combination therapy underwent a significant reduction in serum liver parameters, whereas those on NRTIs alone rebounded to baseline. Herein, we compare clinical experience in the experimental use of antiretroviral agents in patients with PBC with the broader experience of using these agents in people living with HIV infection. While the incidence of gastrointestinal side effects in the PBC population appears somewhat increased compared to those with HIV infection, the clinical improvement observed in patients with PBC suggests that further studies using the newer and better tolerated antiretroviral agents are warranted.
Highlights
Primary biliary cholangitis (PBC) is a complex autoimmune liver disease that predominantly occurs in women [1,2]
The human betaretrovirus was first characterized in patients with breast cancer over 50 years ago, when evidence of B-type particles resembling mammary tumor virus (MMTV) was detected in the milk of 60% of patients with breast cancer [15,16]
The hepatic biochemistry improved considerably with the institution of a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) and the protease inhibitor (PI) lopinavir boosted with ritonavir (LPV/r)
Summary
Primary biliary cholangitis (PBC) is a complex autoimmune liver disease that predominantly occurs in women [1,2]. Autoimmunity is commonly thought to cause disease, studies using immunosuppression and biological therapy have been inconclusive, and individual treatments have not been adopted because of toxicity or a lack of efficacy [4,5]. There is no curative therapy, and there is a definitive need for better strategies to manage the symptoms of fatigue and itch that commonly occur in patients with PBC. Post-transplant disease recurrence is more suggestive of an infectious disease process in the allograft because an autoimmune attack is less likely shortly after transplantation when immunosuppression is highest [7]. It is of interest that combination antiretroviral therapy (cART) has shown some utility in reversing cholangitis in patients with PBC who experience disease recurrence following liver transplantation (Figure 1) [8]
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