View source for 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<ref> 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.</ref>
**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.<ref name="Margolis">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.</ref>
**Variable onset of mitochondrial toxicity, and not at any set point in NRTI use. <ref name="Margolis" />

==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. <ref name="Dragovic">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.</ref>


==Risk Factors==
*Use of stavudine and didanosine containing regimens
*CD4 count <200 <ref name="Dragovic" />
**Additional studies cite a CD4 count less than 500 as a risk factor.<ref>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.</ref>
*Female 2.5x male<ref name="Dragovic" />
*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<ref> 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.</ref>

==Differential Diagnosis==
*Sepsis
*Ischemia

==Evaluation==
*Creatinine clearance, as renal failure is a significant risk factor for the development of lactic acidosis from hyperlactemia. .<ref>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.</ref>
*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<ref name="Woo"> 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.</ref>)
*Cessation of offending drug
*Normal saline
*Anecdotal evidence to support Riboflavin (50mg/day), and/or thiamine (100mg BID) <ref name="Woo" />
*Stop all anti-retrovirals until lactate normalization. .<ref name="Margolis" />
===Non Emergent===
*Consider antioixidant supplementation to reduce oxidative stress and hyperlactemia<ref> 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.</ref>

==Disposition==


==See Also==


==References==
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