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Table of Contents

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Gastrointestinal Effects

(Last updated: March 5, 2015; last reviewed: March 5, 2015)

Table 13c. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Gastrointestinal Effects
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/
Monitoring
Management
Nausea/Vomiting Principally ZDV and PIs (e.g., LPV/r, RTV), but can occur with all ARVs

Onset:

  • Early

Presentation:

  • Nausea, emesis—may be associated with anorexia and/or abdominal pain.
Varies with ARV agent; 10% to 30% in some series
Unknown Instruct patient to take PIs with food.

Generally improves with time; monitor for weight loss, ARV adherence.
Reassure patient/caretaker that nausea and vomiting will likely decrease over time.

Provide supportive care, including instruction on dietary modification.

Although antiemetics are not generally indicated, they may be useful in extreme or persistent cases.
Diarrhea PIs (particularly NFV, LPV/r, FPV/r), buffered ddI, INSTI
 Onset:
  • Early

Presentation:

  • Generally soft, more frequent stools
     
Varies with ARV agent; 10% to 30% in some series Unknown Generally improves with time (usually over 6–8 weeks); monitor for weight loss, dehydration. Exclude infectious causes of diarrhea.

Although data in children on treatment of ARV-associated diarrhea are lacking, dietary modification, use of calcium carbonate (should not be used with DTG), bulk-forming agents (psyllium), or antimotility agents (loperamide) may be helpful. 

While there are few published data on its use, crofelemer is FDA-approved for treatment of ART-associated diarrhea in adults but not in children.
Pancreatitis
ddI, d4T (especially concurrently or with TDF), boosted PIs 

Reported, albeit rarely, with most ARVs
 

Onset:

  • Any time, usually after months of therapy

Presentation:

  • Emesis, abdominal pain, elevated amylase and lipase (Asymptomatic hyperamylasemia or elevated lipase do not in and of themselves indicate pancreatitis.)
<2% in recent series.

Frequency was higher in the past with higher dosing of ddI.
 
Concomitant treatment with other medications associated with pancreatitis (e.g., TMP-SMX, pentamidine, ribavirin)

Hyper-triglyceridemia

Advanced disease

Previous episode of pancreatitis
 
Avoid use of ddI in patients with a history of pancreatitis. Discontinue offending agent—avoid reintroduction.

Manage symptoms of acute episode.

If associated with hyper-triglyceridemia, consider interventions to lower TG levels.
Key to Acronyms: ART = antiretroviral therapy; ARV = antiretroviral; d4T = stavudine; ddI = didanosine; DTG = dolutegravir; FDA = Food and Drug Administration; FPV/r = fosamprenavir/ritonavir; LPV/r = ritonavir-boosted lopinavir; NFV = nelfinavir; PI = protease inhibitor; RTV = ritonavir; TDF = tenofovir disoproxil fumarate; TG = triglyceride; TMP-SMX = trimethoprim sulfamethoxazole; ZDV = zidovudine

References

  1. Buck WC, Kabue MM, Kazembe PN, Kline MW. Discontinuation of standard first-line antiretroviral therapy in a cohort of 1434 Malawian children. J Int AIDS Soc. 2010;13:31. Available at http://www.ncbi.nlm.nih.gov/pubmed/20691049.
  2. Kumarasamy N, Venkatesh KK, Devaleenol B, Poongulali S, Mothi SN, Solomon S. Safety, tolerability and effectiveness of generic HAART in HIV-infected children in South India. J Trop Pediatr. 2009;55(3):155-159. Available at http://www.ncbi.nlm.nih.gov/pubmed/18829638.
  3. Nachman SA, Chernoff M, Gona P, et al. Incidence of noninfectious conditions in perinatally HIV-infected children and adolescents in the HAART era. Arch Pediatr Adolesc Med. 2009;163(2):164-171. Available at http://www.ncbi.nlm.nih.gov/pubmed/19188649.
  4. Hoffmann CJ, Fielding KL, Charalambous S, et al. Antiretroviral therapy using zidovudine, lamivudine, and efavirenz in South Africa: tolerability and clinical events. AIDS. 2008;22(1):67-74. Available at http://www.ncbi.nlm.nih.gov/pubmed/18090393.
  5. Malan N, Su J, Mancini M, et al. Gastrointestinal tolerability and quality of life in antiretroviral-naive HIV-1-infected patients: data from the CASTLE study. AIDS Care. 2010;22(6):677-686. Available at http://www.ncbi.nlm.nih.gov/pubmed/20467943.
  6. Manfredi R, Calza L. HIV infection and the pancreas: risk factors and potential management guidelines. Int J STD AIDS. 2008;19(2):99-105. Available at http://www.ncbi.nlm.nih.gov/pubmed/18334062.
  7. Croxtall JD, Perry CM. Lopinavir/Ritonavir: a review of its use in the management of HIV-1 infection. Drugs. 2010;70(14):1885-1915. Available at http://www.ncbi.nlm.nih.gov/pubmed/20836579.
  8. Turner MJ, Angel JB, Woodend K, Giguere P. The efficacy of calcium carbonate in the treatment of protease inhibitor-induced persistent diarrhea in HIV-infected patients. HIV Clin Trials. 2004;5(1):19-24. Available at http://www.ncbi.nlm.nih.gov/pubmed/15002083.
  9. Heiser CR, Ernst JA, Barrett JT, French N, Schutz M, Dube MP. Probiotics, soluble fiber, and L-Glutamine (GLN) reduce nelfinavir (NFV)- or lopinavir/ritonavir (LPV/r)-related diarrhea. J Int Assoc Physicians AIDS Care (Chic). 2004;3(4):121-129. Available at http://www.ncbi.nlm.nih.gov/pubmed/15768732.
  10. 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.
  11. Wegzyn CM, Fredrick LM, Stubbs RO, Woodward WC, Norton M. Diarrhea Associated with Lopinavir/Ritonavir-Based Therapy: Results of a Meta-Analysis of 1469 HIV-1-Infected Participants. J Int Assoc Physicians AIDS Care (Chic). 2012;11(4):252-259. Available at http://www.ncbi.nlm.nih.gov/pubmed/22544446.
  12. Oumar AA, Diallo K, Dembele JP, et al. Adverse drug reactions to antiretroviral therapy: prospective study in children in sikasso (mali). J Pediatr Pharmacol Ther. 2012;17(4):382-388. Available at http://www.ncbi.nlm.nih.gov/pubmed/23411444.
  13. MacArthur RD, DuPont HL. Etiology and pharmacologic management of noninfectious diarrhea in HIV-infected individuals in the highly active antiretroviral therapy era. Clin Infect Dis. 2012;55(6):860-867. Available at http://www.ncbi.nlm.nih.gov/pubmed/22700829.
  14. Patel TS, Crutchley RD, Tucker AM, Cottreau J, Garey KW. Crofelemer for the treatment of chronic diarrhea in patients living with HIV/AIDS. HIV/AIDS. 2013;5:153-162. Available at http://www.ncbi.nlm.nih.gov/pubmed/23888120.
  15. Wattanutchariya N, Sirisanthana V, Oberdorfer P. Effectiveness and safety of protease inhibitor-based regimens in HIV-infected Thai children failing first-line treatment. HIV Med. 2013;14(4):226-232. Available at http://www.ncbi.nlm.nih.gov/pubmed/23094820.
  16. Van Dyke RB, Wang L, Williams PL, Pediatric ACTGCT. Toxicities associated with dual nucleoside reverse-transcriptase inhibitor regimens in HIV-infected children. J Infect Dis. 2008;198(11):1599-1608. Available at http://www.ncbi.nlm.nih.gov/pubmed/19000014.
  17. Cahn P, Pozniak AL, Mingrone H, et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013;382(9893):700-708. Available at http://www.ncbi.nlm.nih.gov/pubmed/23830355.

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