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Updated Pediatric ARV Guidelines

Updates to the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection were released on Thursday, November 1, 2012. Please send your comments to ContactUs@aidsinfo.nih.gov by November 15, 2012.

Corrections were made to the guideline. For a description of the changes, please see the correction notice.

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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Nephrotoxic Effects

(Last updated:11/1/2012; last reviewed:11/1/2012)

Table 17i. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Nephrotoxic Effects
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Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/ Monitoring Management
Urolithiasis/ nephrolithiasis IDV, ATV Onset:
Weeks to months after starting therapy

Clinical findings:
Crystalluria, hematuria, pyuria, flank pain, sometimes increased creatinine

 IDV-related nephrolithiasis is more common in adults (4%–43%) than in children (0%–20%).

ATV nephrolithiasis rare

 In adults, high serum IDV concentrations and elevated urine pH (>5.7) associated with persistent pyuria.

Unknown in children.

 Prevention:
Maintain adequate hydration.

Monitoring:
Obtain urinalysis at least every 6–12 months.

 Provide adequate hydration and pain control; consider using alternative ARV agent.
Renal
dysfunction		 TDF Onset:
Variable; in adults, weeks to months after initiation of therapy. Hypophosphatemia appears at a median of 18 months.

Presentation:
Renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria

 Adults:
~2% with increased serum creatinine; ~0.5% with severe renal complications

Children:
~4% with hypophosphatemia or proximal tubulopathy;
25% to 78% with severe proteinuria (may be confounded by advanced HIV infection in children studied, and concomitant use of ddI)

 Risk may be increased in children aged >6 years, black race, Hispanic/Latino ethnicity, and by advanced HIV infection, concurrent use of ddI or PIs (especially LPV/r), and pre-existing renal dysfunction). Urinalysis, measurement of serum creatinine, calcium, and phosphorus and determination of spot urine protein/creatinine ratios at least every 6–12 months. If TDF is the likely cause, consider using alternative medication.
IDV Renal cortical atrophy, acute renal failure Rare Unknown Unknown If IDV is likely cause, consider using alternative medication.

Key to Acronyms: ARV = antiretroviral, ATV = atazanavir, ddI = didanosine, IDV = indinavir, LPV/r = lopinavir/ritonavir, PI = protease inhibitor, TDF = tenofovir disoproxil fumarate

References

  1. Andiman WA, Chernoff MC, Mitchell C, et al. Incidence of persistent renal dysfunction in human immunodeficiency virus-infected children: associations with the use of antiretrovirals, and other nephrotoxic medications and risk factors. Pediatr Infect Dis J. Jul 2009;28(7):619-625. Available at http://www.ncbi.nlm.nih.gov/pubmed/19561425.
  2. Brennan A, Evans D, Fox M, et al. Renal Insufficiency, Nephrotoxicity, and Mortality among HIV-infected Adults on TDF in a South African Cohort: A Marginal Structural Models Analysis. Abstract 840. 18th Conference on Retroviruses and Opportunistic Infections (CROI); February 27-March 3, 2011; Boston, MA. Available at:   http://www.retroconference.org/2011/Abstracts/41417.htm.
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  8. van Rossum AM, Dieleman JP, Fraaij PL, et al. Indinavir-associated asymptomatic nephrolithiasis and renal cortex atrophy in two HIV-1 infected children. AIDS. Sep 7 2001;15(13):1745-1747. Available at http://www.ncbi.nlm.nih.gov/pubmed/11546957.
  9. van Rossum AM, Dieleman JP, Fraaij PL, et al. Persistent sterile leukocyturia is associated with impaired renal function in human immunodeficiency virus type 1-infected children treated with indinavir. Pediatrics. Aug 2002;110(2 Pt 1):e19. Available at http://www.ncbi.nlm.nih.gov/pubmed/12165618.
  10. Hall AM, Hendry BM, Nitsch D, Connolly JO. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. American journal of kidney diseases : the official journal of the National Kidney Foundation. May 2011;57(5):773-780. Available at http://www.ncbi.nlm.nih.gov/pubmed/21435764.
  11. Herlitz LC, Mohan S, Stokes MB, Radhakrishnan J, D'Agati VD, Markowitz GS. Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities. Kidney international. Dec 2010;78(11):1171-1177. Available at http://www.ncbi.nlm.nih.gov/pubmed/20811330.
  12. Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis. Sep 1 2010;51(5):496-505. Available at http://www.ncbi.nlm.nih.gov/pubmed/20673002.
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