HAART-induced lactic acidosis

Background
  • Nucleoside Reverse Transcriptase Inhibitors are associated with hyperlactemia and lactic acidosis
    • NRTI also cause pancreatitis, myopathy, peripheral neuropathy, anemia, neutropenia, hepatic toxicity[1]
    • Specifically didanosine (ddI) and stavudine (d4T)
    • These medicines are no longer first-line agents in the US and Europe, but are in low-middle income countries
  • Adverse effects of NRTI is by way of mitochondrial toxicity.
    • NRTI inhibit human DNA polymerase gamma, a key enzyme for mitochondrial replication.
    • Impaired electron transport chain, leading to leakage of electrons and increased production of reactive oxygen species.[2]
    • Variable onset of mitochondrial toxicity, and not at any set point in NRTI use. [2]

Risk Factors
  • Use of stavudine and didanosine containing regimens
  • CD4 count <200 [3]
    • Additional studies cite a CD4 count less than 500 as a risk factor.[4]
  • Female 2.5x male[3]
  • Plasma Triglycerides >2.2mmol/L
  • Age, as the risk of hyperlactemia increases 50% with every 10 years of aging
  • Lipodystrophy and lipoatrophy
    • Associated with dyslipidemia and insulin resistance[5]

Clinical Features
  • Fatigue, malaise
  • Nausea and or vomiting
  • Unexplained mental status changes
  • Neurologic Deficits, seizures
  • Dysrhythmias
  • Heart failure
  • Weight gain/weight loss
  • Tachypnea, dyspnea
  • Renal abnormalities
  • Since the symptoms are non-specific, most patients present with advanced symptoms and the more serious lactic acidosis. [3]

Differential Diagnosis
  • Sepsis
  • Ischemia

HIV associated conditions

Evaluation
  • Creatinine clearance, as renal failure is a significant risk factor for the development of lactic acidosis from hyperlactemia. .[7]
  • CBC
  • Liver Function Test, as hepatic dysfunction precludes oxidation of lactate, thus resulting in elevated lactate levels in the blood
  • Electrolytes
  • Urinalysis
  • Lactic Acid level
  • ABG
  • Lipase
  • CPK

Management

Emergent
  • Sodium bicarb (judicious doses[8])
  • Cessation of offending drug
  • Normal saline
  • Anecdotal evidence to support Riboflavin (50mg/day), and/or thiamine (100mg BID) [8]
  • Stop all anti-retrovirals until lactate normalization[2]

Non Emergent
  • Consider antioixidant supplementation to reduce oxidative stress and hyperlactemia[9]

Disposition
  • Admit

See Also

References
  1. Lee WM, Dienstag JL. Lee W.M., Dienstag J.L. Lee, William M., and Jules L. Dienstag.Toxic and Drug-Induced Hepatitis. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J Eds. Dennis Kasper, et al.eds. Harrison's Principles of Internal Medicine, 19e New York, NY: McGraw-Hill; 2014. http://accessmedicine.mhmedical.com/content.aspx?bookid=1130&sectionid=79748661. Accessed August 22, 2017.
  2. Margolis AM, Heverling H, Pham PA, Stolbach A. A review of the toxicity of HIV medications. J Med Toxicol. 2014 Mar;10(1):26-39. doi: 10.1007/s13181-013-0325-8. Review. PubMed PMID: 23963694; PubMed Central PMCID: PMC3951641.
  3. Dragovic G, Jevtovic D. The role of nucleoside reverse transcriptase inhibitors usage in the incidence of hyperlactatemia and lactic acidosis in HIV/AIDS patients. Biomed Pharmacother. 2012 Jun;66(4):308-11. doi: 10.1016/j.biopha.2011.09.016. Epub 2012 May 15. PubMed PMID: 22658063.
  4. Bonnet F, Balestre E, Bernardin E, Pellegrin JL, Neau D, Dabis F; Groupe d'Epidémiologie Clinique du SIDA en Aquitaine. Risk factors for hyperlactataemia in HIV-infected patients, Aquitaine Cohort, 1999--2003. Antivir Chem Chemother. 2005;16(1):63-7. PubMed PMID: 15739622.
  5. Lewis W, Currie PF. HIV/AIDS AND THE CARDIOVASCULAR SYSTEM. In: Fuster V, Harrington RA, Narula J, Eapen ZJ. eds. Hurst's The Heart, 14e New York, NY: McGraw-Hill; . http://accessmedicine.mhmedical.com/content.aspx?bookid=2046&sectionid=155644091. Accessed August 22, 2017.
  6. Gutteridge, David L MD, MPH, Egan, Daniel J. MD. The HIV-Infected Adult Patient in The Emergency Department: The Changing Landscape of the Disease. Emergency Medicine Practice: An Evidence-Based Approach to Emergency Medicine. Vol 18, Num 2. Feb 2016.
  7. Bonnet F, Balestre E, Bernardin E, Pellegrin JL, Neau D, Dabis F; Groupe d'Epidémiologie Clinique du SIDA en Aquitaine. Risk factors for hyperlactataemia in HIV-infected patients, Aquitaine Cohort, 1999--2003. Antivir Chem Chemother. 2005;16(1):63-7. PubMed PMID: 15739622.
  8. Woo OF. Woo O.F. Woo, Olga F.Chapter 23. Antiviral and Antiretroviral Agents. In: Olson KR. Olson K.R. Ed. Kent R. Olson.eds. Poisoning & Drug Overdose, 6e New York, NY: McGraw-Hill; 2012. http://accessmedicine.mhmedical.com/content.aspx?bookid=391&sectionid=42069837. Accessed August 22, 2017.
  9. Lopez O, Bonnefont-Rousselot D, Edeas M, Emerit J, Bricaire F. Could antioxidant supplementation reduce antiretroviral therapy-induced chronic stable hyperlactatemia? Biomed Pharmacother. 2003 May-Jun;57(3-4):113-6. PubMed PMID:12818471.
This article is issued from Wikem. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.