Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

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Management of Medication Toxicity or Intolerance

Lactic Acidosis

Last Updated: May 22, 2018; Last Reviewed: May 22, 2018

References

General Reviews

  1. Fortuny C, Deya-Martinez A, Chiappini E, Galli L, de Martino M, Noguera-Julian A. Metabolic and renal adverse effects of antiretroviral therapy in HIV-infected children and adolescents. Pediatr Infect Dis J. 2015;34(5 Suppl 1):S36-43. Available at http://www.ncbi.nlm.nih.gov/pubmed/25629891.
  2. Margolis AM, Heverling H, Pham PA, Stolbach A. A review of the toxicity of HIV medications. J Med Toxicol. 2014;10(1):26-39. Available at http://www.ncbi.nlm.nih.gov/pubmed/23963694.
  3. Tukei VJ, Asiimwe A, Maganda A, et al. Safety and tolerability of antiretroviral therapy among HIV-infected children and adolescents in Uganda. J Acquir Immune Defic Syndr. 2012;59(3):274-280. Available at http://www.ncbi.nlm.nih.gov/pubmed/22126740.

Fatal Lactic Acidosis

  1. Arenas-Pinto A, Grant A, Bhaskaran K, et al. Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis. Antivir Ther. 2011;16(2):219-226. Available at http://www.ncbi.nlm.nih.gov/pubmed/21447871.
  2. Leung L, Wilson D, Manini AF. Fatal toxicity from symptomatic hyperlactataemia: a retrospective cohort study of factors implicated with long-term nucleoside reverse transcriptase inhibitor use in a South African hospital. Drug Saf. 2011;34(6):521-527. Available at http://www.ncbi.nlm.nih.gov/pubmed/21488705.
  3. Manosuthi W, Prasithsirikul W, Chumpathat N, et al. Risk factors for mortality in symptomatic hyperlactatemia among HIV-infected patients receiving antiretroviral therapy in a resource-limited setting. Int J Infect Dis. 2008;12(6):582-586. Available at http://www.ncbi.nlm.nih.gov/pubmed/18337140.

Risk Factors

  1. Aperis G, Paliouras C, Zervos A, Arvanitis A, Alivanis P. Lactic acidosis after concomitant treatment with metformin and tenofovir in a patient with HIV infection. J Ren Care. 2011;37(1):25-29. Available at http://www.ncbi.nlm.nih.gov/pubmed/21288314.
  2. Lopinavir/ritonavir [package insert]. Food and Drug Administration. 2016. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021251s052_021906s046lbl.pdf.
  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;66(4):308-311. Available at http://www.ncbi.nlm.nih.gov/pubmed/22658063.
  4. Feeney ER, Chazallon C, O'Brien N, et al. Hyperlactataemia in HIV-infected subjects initiating antiretroviral therapy in a large randomized study (a substudy of the INITIO trial). HIV Med. 2011;12(10):602-609. Available at http://www.ncbi.nlm.nih.gov/pubmed/21599820.
  5. Firnhaber C, Smeaton LM, Grinsztejn B, et al. Differences in antiretroviral safety and efficacy by sex in a multinational randomized clinical trial. HIV Clin Trials. 2015;16(3):89-99. Available at https://www.ncbi.nlm.nih.gov/pubmed/25979186.
  6. Fortuin-de Smidt M, de Waal R, Cohen K, et al. First-line antiretroviral drug discontinuations in children. PLoS One. 2017;12(2):e0169762. Available at https://www.ncbi.nlm.nih.gov/pubmed/28192529.
  7. Lim TY, Poole RL, Pageler NM. Propylene glycol toxicity in children. J Pediatr Pharmacol Ther. 2014;19(4):277-282. Available at https://www.ncbi.nlm.nih.gov/pubmed/25762872.
  8. Mamiafo CT, Moor VJ, Nansseu JR, Pieme CA, Tayou C, Yonkeu JN. Hyperlactatemia in a group of HIV patients living in Yaounde-Cameroon. AIDS Res Ther. 2014;11(1):2. Available at http://www.ncbi.nlm.nih.gov/pubmed/24428886.
  9. Maskew M, Westreich D, Fox MP, Maotoe T, Sanne IM. Effectiveness and safety of 30 mg versus 40 mg stavudine regimens: a cohort study among HIV-infected adults initiating HAART in South Africa. J Int AIDS Soc. 2012;15(1):13. Available at http://www.ncbi.nlm.nih.gov/pubmed/22410312.
  10. Matthews LT, Giddy J, Ghebremichael M, et al. A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy. PLoS One. 2011;6(4):e18736. Available at http://www.ncbi.nlm.nih.gov/pubmed/21494566.
  11. Menezes CN, Maskew M, Sanne I, Crowther NJ, Raal FJ. A longitudinal study of stavudine-associated toxicities in a large cohort of South African HIV infected subjects. BMC Infect Dis. 2011;11:244. Available at http://www.ncbi.nlm.nih.gov/pubmed/21923929.
  12. Moren C, Noguera-Julian A, Garrabou G, et al. Mitochondrial evolution in HIV-infected children receiving first- or second-generation nucleoside analogues. J Acquir Immune Defic Syndr. 2012;60(2):111-116. Available at http://www.ncbi.nlm.nih.gov/pubmed/22362155.
  13. Osler M, Stead D, Rebe K, Meintjes G, Boulle A. Risk factors for and clinical characteristics of severe hyperlactataemia in patients receiving antiretroviral therapy: a case-control study. HIV Med. 2010;11(2):121-129. Available at http://www.ncbi.nlm.nih.gov/pubmed/19702629.
  14. Palmer M, Chersich M, Moultrie H, Kuhn L, Fairlie L, Meyers T. Frequency of stavudine substitution due to toxicity in children receiving antiretroviral treatment in sub-Saharan Africa. AIDS. 2013;27(5):781-785. Available at http://www.ncbi.nlm.nih.gov/pubmed/23169331.
  15. Phan V, Thai S, Choun K, Lynen L, van Griensven J. Incidence of treatment-limiting toxicity with stavudine-based antiretroviral therapy in Cambodia: a retrospective cohort study. PLoS One. 2012;7(1):e30647. Available at http://www.ncbi.nlm.nih.gov/pubmed/22303447.
  16. Tetteh RA, Nartey ET, Lartey M, et al. Association between the occurrence of adverse drug events and modification of first-line highly active antiretroviral therapy in Ghanaian HIV Patients. Drug Saf. 2016;39(11):1139-1149. Available at https://www.ncbi.nlm.nih.gov/pubmed/27638659.
  17. Wester CW, Eden SK, Shepherd BE, et al. Risk factors for symptomatic hyperlactatemia and lactic acidosis among combination antiretroviral therapy-treated adults in Botswana: results from a clinical trial. AIDS Res Hum Retroviruses. 2012;28(8):759-765. Available at http://www.ncbi.nlm.nih.gov/pubmed/22540188.

Monitoring and Management

  1. Barlow-Mosha L, Eckard AR, McComsey GA, Musoke PM. Metabolic complications and treatment of perinatally HIV-infected children and adolescents. J Int AIDS Soc. 2013;16:18600. Available at http://www.ncbi.nlm.nih.gov/pubmed/23782481.
  2. Chagoma N, Mallewa J, Kaunda S, et al. Longitudinal lactate levels from routine point-of-care monitoring in adult Malawian antiretroviral therapy patients: associations with stavudine toxicities. Trans R Soc Trop Med Hyg. 2013;107(10):615-619. Available at http://www.ncbi.nlm.nih.gov/pubmed/23926161.
  3. Claessens YE, Cariou A, Monchi M, et al. Detecting life-threatening lactic acidosis related to nucleoside-analog treatment of human immunodeficiency virus-infected patients, and treatment with L-carnitine. Crit Care Med. 2003;31(4):1042-1047. Available at http://www.ncbi.nlm.nih.gov/pubmed/12682470.
  4. Kraut JA, Madias NE. Lactic acidosis. N Engl J Med. 2014;371(24):2309-2319. Available at http://www.ncbi.nlm.nih.gov/pubmed/25494270.
  5. Marfo K, Garala M, Kvetan V, Gasperino J. Use of Tris-hydroxymethyl aminomethane in severe lactic acidosis due to highly active antiretroviral therapy: a case report. J Clin Pharm Ther. 2009;34(1):119-123. Available at http://www.ncbi.nlm.nih.gov/pubmed/19125910.

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