Clinical Syndromes and Consequences of Antiretroviral-Related Hepatotoxicity

Department of Internal Medicine, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA.
Hepatology (Impact Factor: 11.06). 09/2010; 52(3):1143-55. DOI: 10.1002/hep.23716
Source: PubMed


Highly active antiretroviral therapy (HAART)-related hepatotoxicity complicates the management of patients infected with human immunodeficiency virus (HIV), increases medical costs, alters the prescription patterns, and affects the guideline recommendations. Among the clinical consequences derived from HAART-related liver toxicity, hypersensitivity reactions and lactic acidosis are recognized as acute events with potential to evolve into fatal cases, whereas there seems to be other syndromes not as well characterized but of equal concern as possible long-term liver complications. Belonging to the latter category of syndrome, HAART-related nonalcoholic steatohepatitis, liver fibrosis, portal hypertension, and nodular regenerative hyperplasia are discussed in this review. Updated information on liver toxicity of current antiretroviral drugs, including the most recently licensed, is provided. Management and prevention of liver toxicity among HIV-infected patients treated with HAART are reviewed as well.

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    • "However, the need for lifelong therapy and difficulties in adherence to medication regimes are likely to lead to the emergence of drug-resistant HIV-1 strains. Long-term side effects, such as cardiovascular disease, hepatotoxicity and dementia, have been reported in association with HIV-1 infection.4,5,6 The most serious deficiency of ART is that it cannot eradicate latent virus.7 Once the treatment is interrupted, a replicable HIV-1 reemerges. "
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    ABSTRACT: MazF, an endoribonuclease encoded by Escherichia coli, specifically cleaves the ACA (adenine-cytosine-adenine) sequence of single-stranded RNAs. Conditional expression of MazF under the control of the HIV-1 LTR promoter rendered CD4(+) T cells resistant to HIV-1 replication without affecting cell growth. To investigate the safety, persistence and efficacy of MazF-modified CD4(+) T cells in a nonhuman primate model in vivo, rhesus macaques were infected with a pathogenic simian/human immunodeficiency virus (SHIV) and transplanted with autologous MazF-modified CD4(+) T cells. MazF-modified CD4(+) T cells were clearly detected throughout the experimental period of more than 6 months. The CD4(+) T cell count values increased in all four rhesus macaques. Moreover, the transplantation of the MazF-modified CD4(+) T cells was not immunogenic, and did not elicit cellular or humoral immune responses. These data suggest that the autologous transplantation of MazF-modified CD4(+) T cells in the presence of SHIV is effective, safe and not immunogenic, indicating that this is an attractive strategy for HIV-1 gene therapy.
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    • "Among the indirect mechanisms, the most important is based on an impaired T-cell response to HCV [4], which can be only partially reverted by antiretroviral treatment [2]; in fact, end-stage liver disease actually represents the leading cause of mortality among HIV-positive patients, regardless of the use of ART [5]. Moreover, HIV itself and certain antiretrovirals may contribute to liver disease by inducing the metabolic syndrome [6]. In addition, HIV infection of the gastrointestinal tract amplifies microbial translocation which can stimulate hepatocytes, Kupffer cells (KCs), and hepatic stellate cells (HSC) to produce pro-inflammatory cytokines and chemokines. "
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    • "In this sense, the study of Guaraldi et al. (2008) suggested that NAFLD is common in HIV patients who have traditional risk factors but this study also highlights that treatment with NRTIs is also an important independent risk factor, increasing up to 11% the risk of developing hepatic impairment for each year of use [60]. Some protease inhibitors are also hepatotoxic, in particular full-dose ritonavir and tipranavir [61]. However, the generalized use of only boosting concentrations of ritonavir prevents the liver toxicity. "
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