Adverse effects of antiretroviral drugs on HIV-1-infected and -uninfected human monocyte-derived macrophages

Journal of Acquired Immune Deficiency Syndromes : JAIDS
Rula AzzamSuzanne M Crowe

Abstract

Antiretroviral drugs approved for treatment of HIV-1 infection include nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs). Use of these drugs in combinations (highly active antiretroviral therapy) has delayed disease progression. However, long-term therapy is associated with potentially serious adverse effects. NRTIs are thought to contribute to these adverse effects via depletion of mtDNA. Inasmuch as macrophages (major targets for HIV-1) are highly metabolically active with large numbers of mitochondria, we investigated the effects of NRTIs (didanosine, stavudine, lamivudine, and zidovudine) on the viability and function of HIV-1-infected and -uninfected human monocyte-derived macrophages (MDMs). We demonstrate that the combinations didanosine/stavudine and lamivudine/zidovudine decrease mtDNA content in MDMs, with HIV-1-infected MDMs displaying a greater reduction than uninfected cells. This decrease correlated with decreased complement-mediated phagocytosis (C'MP) by MDMs, a process dependent on mitochondrial function. Inasmuch as PIs have previously been reported to interact with cellular proteases and given that cellular proteases are involved in the phagocytic process, we investigated the e...Continue Reading

References

Jan 1, 1975·The Journal of Experimental Medicine·D B Drath, M L Karnovsky
May 1, 1992·The Annals of Pharmacotherapy·M J SheltonG D Morse
Dec 1, 1992·AIDS Research and Human Retroviruses·P J BugelskiR Kirsh
Feb 1, 1992·Clinical Immunology and Immunopathology·F CapsoniC Zanussi
Jan 1, 1990·Pharmacology & Therapeutics·G E Wright, N C Brown
Apr 19, 1990·The New England Journal of Medicine·M C DalakasJ L Griffin
Jan 1, 1968·Advances in Immunology·Z A Cohn
Dec 1, 1994·Antimicrobial Agents and Chemotherapy·J L MartinJ E Reardon
Sep 1, 1994·The Journal of Cell Biology·M SomasundaranR H Singer
Jul 15, 1993·Biochemical and Biophysical Research Communications·J S Modica-Napolitano
Dec 1, 1995·Australian and New Zealand Journal of Medicine·S M Crowe
Mar 1, 1996·Cell Biochemistry and Function·P NewsholmeR Curi
Jul 15, 1997·Annals of Internal Medicine·J B KoppJ Falloon
Aug 21, 1997·Biochimica Et Biophysica Acta·A AntonelliM Magnani
Oct 27, 1997·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·J S BernsJ Turner
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·P AndréV Lotteau
May 4, 1999·The American Journal of Medicine·M A Perazella
Nov 24, 1999·The Journal of Biological Chemistry·R RossignolT Letellier
Feb 19, 2000·Antimicrobial Agents and Chemotherapy·X R Pan-ZhouV M Darley-Usmar
Feb 19, 2000·Antimicrobial Agents and Chemotherapy·G GattiN Principi
Aug 12, 2000·Platelets·S M SchoenwaelderS P Jackson
Sep 8, 2000·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·R F GagnonC M Tsoukas
Jul 13, 2001·Antiviral Research·R G JainJ M Lenhard

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Citations

Jul 2, 2016·Neurotoxicity Research·Ankit ShahAnil Kumar
Dec 31, 2015·PloS One·Andrea L Martinez-SkinnerHoward E Gendelman
Feb 7, 2008·Journal of Leukocyte Biology·Eva PericoliniAnna Vecchiarelli
Nov 4, 2010·Antiviral Chemistry & Chemotherapy·Serguei V VinogradovMadapathage T Senanayake
Apr 3, 2013·Journal of Proteome Research·Andrea L Martinez-SkinnerHoward E Gendelman
Oct 22, 2009·Antiviral Chemistry & Chemotherapy·Christina Gavegnano, Raymond F Schinazi

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