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Table of Contents

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs)

Tenofovir DF

(Last updated: April 26, 2016; last reviewed: April 26, 2016)

Tenofovir Disoproxil Fumarate (TDF, Viread)
Tenofovir Disoproxil Fumarate (TDF, Viread)
For additional information see Drugs@FDA: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
Formulations
Oral Powder: 40 mg per 1 g of oral powder (1 level scoop = 1 g oral powder; supplied with dosing scoop)
Tablets: 150 mg, 200 mg, 250 mg, and 300 mg
Fixed-dose Combination Tablets
  • [Truvada low strength tablet]
    • Emtricitabine 100 mg plus tenofovir disoproxil fumarate (TDF) 150 mg
    • Emtricitabine 133 mg plus TDF 200 mg
    • Emtricitabine 167 mg plus TDF 250 mg
  • [Truvada tablet] Emtricitabine 200 mg plus TDF 300 mg
  • [Atripla] Efavirenz 600 mg plus emtricitabine 200 mg plus TDF 300 mg
  • [Complera] Emtricitabine 200 mg plus rilpivirine 25 mg plus TDF 300 mg
  • [Stribild] Elvitegravir 150 mg plus cobicistat 150 mg plus emtricitabine 200 mg plus TDF 300 mg
Dosing Recommendations Selected Adverse Events
Neonate/Infant Dose:
  • Not Food and Drug Administration-approved or recommended for use in neonates/infants aged <2 years.
Pediatric Dose (Aged ≥2 Years to <12 Years)a:
  • 8 mg/kg/dose once daily

TDF Oral Powder Dosing Table
Body Weight
kg
TDF Oral Powder
Once Daily Scoops of Powder
10 to <12 2 scoops (80 mg)
12 to <14 2.5 scoops (100 mg)
14 to <17 3 scoops (120 mg)
17 to <19 3.5 scoops (140 mg)
19 to <22 4 scoops (160 mg)
22 to <24 4.5 scoops (180 mg)
24 to <27 5 scoops (200 mg)
27 to <29 5.5 scoops (220 mg)
29 to <32 6 scoops (240 mg)
32 to <34 6.5 scoops (260 mg)
34 to <35  7 scoops (280 mg)
35 7.5 scoops (300 mg)


TDF Tablet Dosing Table
(Aged 2 Years and Weighing 17 kg)
Body Weight
kg
TDF Tablet
Once Daily
17 to <22 150 mg
22 to <28 200 mg
28 to <35 250 mg
35 300 mg

Adolescent (Weighing ≥35 kg)a and Adult Dose:

  • TDF 300 mg once daily
Combination Tablets
[Truvada] Emtricitabine plus TDF
Truvada Tablets Dosing Table
Body Weight
kg
FTC/TDF Tablet
Once Daily
17 to <22 One FTC 100 mg/TDF 150 mg tablet
22 to <28 One FTC 133 mg/TDF 200 mg tablet
28 to <35 One FTC 167 mg/TDF 250 mg tablet
≥35 (Adolescent and Adult) One FTC 200 mg/TDF 300 mg tablet

[Atripla] Efavirenz plus Emtricitabine plus TDF
Adolescent (Aged ≥12 years and Weighing ≥40 kg) and Adult Dose
:

  • 1 tablet once daily.
[Complera] Emtricitabine plus Rilpivirine plus TDF
Adolescent (Weighing ≥35 kg) and Adult Dose
:
  • 1 tablet once daily in treatment-naive adults with baseline viral load <100,000 copies/mL or virologically suppressed adults, with no history of virologic failure, resistance to rilpivirine and other ARV drugs, and who are currently on their first or second regimen.
  • Administer with a meal of at least 400 calories.
[Stribild] Elvitegravir plus Cobicistat plus Emtricitabine plus TDF
Adolescent (Weighing >35 kg and Tanner Stage 4 or 5) and Adult Dose:

  • 1 tablet once daily in treatment-naive adults or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Stribild.
  • Administer with food.
  • Asthenia, headache, diarrhea, nausea, vomiting, flatulence
  • Renal insufficiency, proximal renal tubular dysfunction that may include Fanconi syndrome
  • Decreased bone mineral densitya.
Special Instructions
  • Do not crush tablets; TDF oral powder formulation is available for patients unable to swallow tablets.
  • TDF oral powder should be measured only with the supplied dosing scoop: 1 level scoop = 1 g powder = 40 mg TDF.
  • Mix TDF oral powder in 2 to 4 oz of soft food that does not require chewing (e.g., applesauce, yogurt). Administer immediately after mixing to avoid the bitter taste.
  • Do not try to mix the TDF oral powder with liquid. The powder may float on the top even after vigorous stirring.
  • Although TDF can be administered without regard to food, food requirements vary depending on the other antiretroviral (ARV) drugs contained in a combination tablet. For Atripla (administer without food) and Complera (administer with a meal of at least 400 calories), refer to efavirenz or rilpivirine special instructions, respectively.
  • Measure serum creatinine and urine dipstick for protein and glucose before starting a TDF-containing regimen and monitor serum creatinine and urine dipstick for protein and glucose at intervals (see Table 12i) during continued therapy. Measure serum phosphate if clinical suspicion of hypophosphatemia.
  • Screen patients for hepatitis B virus (HBV) infection before use of TDF. Severe acute exacerbation of HBV infection can occur when TDF is discontinued; therefore, in patients with HBV infection, monitor hepatic function for several months after therapy with TDF is stopped.
  • If using Stribild, please see the elvitegravir and cobicistat sections of the drug appendix for additional information.
Metabolism/Elimination
  • Renal excretion
  • Dosing of TDF in patients with renal insufficiency: Decreased dosage should be used in patients with impaired renal function (creatinine clearance <50 mL/min). Consult manufacturer’s prescribing information for adjustment of dosage in accordance with creatinine clearance (CrCl).
  • Atripla and Complera (fixed-dose combinations) should not be used in patients with CrCl <50 mL/min or in patients requiring dialysis.
  • Truvada (fixed-dose combination) should not be used in patients with CrCl <30 mL/min or in patients requiring dialysis.
  • Stribild should not be initiated in patients with estimated CrCl <70 mL/min and should be discontinued in patients with estimated CrCl <50 mL/min.
  • Stribild should not be used in patients with severe hepatic impairment.
 a See text for concerns about decreased BMD, especially in pre-pubertal patients and those in early puberty (Tanner Stages 1 and 2).

Drug Interactions (see also the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents and http://www.hiv-druginteractions.org/)

  • Renal elimination: Drugs that decrease renal function or compete for active tubular secretion could reduce clearance of plasma tenofovir disoproxil fumarate (TDF).
  • Other nucleoside reverse transcriptase inhibitors: Didanosine serum concentrations are increased when the drug is co-administered with TDF and this combination should be avoided if possible because of increase in didanosine toxicity.
  • Protease inhibitors: TDF decreases atazanavir plasma concentrations. Atazanavir without ritonavir should not be co-administered with TDF. In addition, atazanavir and lopinavir/ritonavir increase plasma tenofovir concentrations and could potentiate TDF-associated toxicity.
  • Use of Stribild: If using Stribild, please see the elvitegravir section of the drug appendix for additional information.

Major Toxicities

  • More common: Nausea, diarrhea, vomiting, and flatulence.
  • Less common (more severe): TDF caused bone toxicity (osteomalacia and reduced bone mineral density [BMD]) in animals when given in high doses. Decreases in BMD have been reported in both adults and children taking TDF; the clinical significance of these changes is not yet known. Renal toxicity, including increased serum creatinine, glycosuria, proteinuria, phosphaturia, and/or calciuria and decreases in serum phosphate, has been observed. Patients at increased risk of renal glomerular or tubular dysfunction should be closely monitored. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported.

Resistance

The International Antiviral Society-USA (IAS-USA) maintains a list of updated resistance mutations (see http://iasusa.org/sites/default/files/tam/october_november_2015.pdf#page=10) and the Stanford University HIV Drug Resistance Database offers a discussion of each mutation (see http://hivdb.stanford.edu/DR/).

Pediatric Use

Approval
TDF is Food and Drug Administration (FDA)-approved for use in children aged ≥2 years when used as a component of antiretroviral therapy (ART).

TDF has antiviral activity and efficacy against hepatitis B virus (HBV) and is FDA-approved for HBV treatment for children aged 12 years and older (reviewed in Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Children).

Efficacy in Clinical Trials in Adults Compared to Children and Adolescents

The standard adult dose of TDF approved by the FDA for adults and children aged ≥12 years and weight ≥35 kg is 300 mg once daily; for children aged 2 to 12 years, the FDA-approved TDF dose is 8 mg/kg/dose administered once daily, which closely approximates the dose of 208 mg/m2/dose used in early studies in children.1

In adults, the recommended TDF dose is highly effective.2,3 In children, the published efficacy data are mixed, but potency equal to that in adults is seen in pediatric patients aged 3 to 18 years with susceptible virus. In children aged 2 to <12 years, TDF 8 mg/kg/dose once daily showed non-inferiority to twice-daily zidovudine- or stavudine-containing ART over 48 weeks of randomized treatment.4,5 Virologic success is lower in treatment-experienced patients with extensive drug resistance.6-8

Pharmacokinetics

Relationship of Drug Exposure to Virologic Response
Virologic success is most closely related to intracellular tenofovir diphosphate (TFV-DP) concentrations, and for TDF, intracellular TFV-DP is linked to plasma TFV concentration.9 A modeling study suggests that children and adolescents treated with TDF may have higher intracellular TFV-DP concentrations than adults10 even though plasma TFV concentrations are lower in children and adolescents because renal clearance of TFV is higher in children than in adults.1,11,12

Formulations

Special Considerations
The taste-masked granules that make up the TDF oral powder give the vehicle (e.g., applesauce, yogurt) a gritty consistency. Once mixed in the vehicle, TDF should be administered promptly because, if allowed to sit too long, its taste becomes bitter.

Toxicity

Bone
TDF administration is associated with decreased BMD in both adults13,14 and children.5,15-17 When treated with TDF, younger children in Tanner Stages 1 and 2 may be at higher risk of decreased BMD than children with more advanced pubertal development (i.e., Tanner Stage ≥3).11 Discontinuation of TDF results in partial or complete recovery of BMD.15

In the industry-sponsored study that led to FDA approval of TDF in adolescents aged ≥12 years and weight ≥35 kg, 6 of 33 participants (18%) in the TDF arm experienced a >4% decline in absolute lumbar spine BMD in 48 weeks compared with 1 of 33 participants (3%) in the placebo arm.6

TDF administration disrupts vitamin D metabolism18 and the decrease in BMD associated with TDF initiation was attenuated in adults with co-administration of high doses of vitamin D3 (4000 International Units [IU] daily) and calcium carbonate (1000 mg daily) for the first 48 weeks of TDF treatment.19 During chronic TDF administration, in youth with HIV, supplementation with vitamin D3 (50,000 IU once monthly) was associated with decrease in serum parathyroid hormone;20 the effect on BMD of vitamin D supplementation during chronic TDF administration is under study (Clinicaltrials.gov identifier NCT01751646).

Monitoring Potential Bone Toxicity
The Panel does not recommend routine dual-energy absorptiometry (DXA) monitoring for children or adolescents treated with TDF. Given the potential for BMD loss in children treated with TDF, some experts obtain a DXA before initiation of TDF therapy and approximately 6 months after starting TDF, especially in pre-pubertal patients and those early in puberty (i.e., Tanner Stages 1 and 2). If DXA results are abnormal, consider referral to a subspecialist in pediatric endocrinology or a related field.

Despite the ease of use of a once-daily drug and the efficacy of TDF, the potential for BMD loss during the important period of rapid bone accrual in childhood and early adolescence is concerning and favors use of abacavir (or possibly tenofovir alafenamide [TAF]) in children in Tanner Stages 1-3, because children with perinatally acquired HIV are at risk for low peak bone mass.21,22

Renal
New onset or worsening of renal impairment has been reported in adults23 and children24,25 receiving TDF, with renal toxicity leading to discontinuation of TDF reported in 3.7% (6 of 159) of HIV-1-infected children treated with TDF.8 While TDF is clearly associated with a decline in glomerular filtration rate, the effect is generally small, and severe glomerular toxicity is rare.23,24 Irreversible renal failure is quite rare but has been reported.26

The main target of TDF nephrotoxicity is the renal proximal tubule.24 Case reports highlight the infrequent but most severe manifestations of renal Fanconi syndrome, hypophosphatemia, hypocalcemia, diabetes insipidus, myalgias, bone pain, and fractures.27,28

Subclinical renal tubular damage is more frequent. Increased urinary beta-2 microglobulin was identified in 27% (12 of 44) of children treated with TDF compared with 4% (2 of 48) of children not treated with TDF.29 TDF-associated proteinuria or chronic kidney disease is more common with longer duration of treatment.30,31 Of 89 participants aged 2 to 12 years who received TDF in Gilead study 352 (median drug exposure 104 weeks), 4 were discontinued from the study for renal tubular dysfunction, with the discontinuations occurring between 84 and 156 weeks on TDF therapy.4

Monitoring Potential Renal Toxicity
Because of the potential for TDF to decrease creatinine clearance and to cause renal tubular dysfunction, measurement of serum creatinine and urine dipstick for protein and glucose prior to drug initiation is recommended. In asymptomatic individuals, the optimal frequency for routine monitoring of creatinine and renal tubular function (urine protein and glucose) is unclear. Many panel members monitor creatinine with other blood tests every 3 to 4 months, and urinalysis every 6 to 12 months. Serum phosphate should be measured if clinically indicated; renal phosphate loss can occur in the presence of normal creatinine and the absence of proteinuria. Because nephrotoxicity increases with the duration of TDF treatment, monitoring should be continued during long-term therapy with the drug.

Because renal glomerular damage primarily increases urine concentration of albumin, and proximal renal tubular damage increases urine concentrations of low-molecular-weight proteins like beta-2 microglobulin, the dipstick urinalysis (measuring primarily urine albumin) may be a relatively insensitive marker for TDF-associated tubular damage. Measurement of urine albumin and urine protein, and calculation of the urine albumin to urine protein ratio, can be helpful in identifying the non-albumin proteinuria that is seen in TDF-associated nephrotoxicity.32,33 While these more complex and expensive tests may be used in research settings, in clinical practice, renal tubular damage is perhaps easiest to identify by using a renal dipstick to identify normoglycemic glycosuria and proteinuria.

References 

  1. Hazra R, Balis FM, Tullio AN, et al. Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children. Antimicrob Agents Chemother. 2004;48(1):124-129. Available at http://www.ncbi.nlm.nih.gov/pubmed/14693529.
  2. Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA. 2004;292(2):191-201. Available at http://www.ncbi.nlm.nih.gov/pubmed/15249568.
  3. Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med. 2006;354(3):251-260. Available at http://www.ncbi.nlm.nih.gov/pubmed/16421366.
  4. Saez-Llorens X, Castano E, Rathore M, et al. A randomized, open-label study of the safety and efficacy of switching stavudine or zidovudine to tenofovir disoproxil fumarate in HIV-1-infected children with virologic suppression. Pediatr Infect Dis J. 2015;34(4):376-382. Available at http://www.ncbi.nlm.nih.gov/pubmed/25760565.
  5. Aurpibul L, Cressey TR, Sricharoenchai S, et al. Efficacy, safety and pharmacokinetics of tenofovir disoproxil fumarate in virologic-suppressed HIV-infected children using weight-band dosing. Pediatr Infect Dis J. 2015;34(4):392-397. Available at http://www.ncbi.nlm.nih.gov/pubmed/25760566.
  6. Della Negra M, de Carvalho AP, de Aquino MZ, et al. A randomized study of tenofovir disoproxil fumarate in treatment-experienced HIV-1 infected adolescents. Pediatr Infect Dis J. 2012;31(5):469-473. Available at http://www.ncbi.nlm.nih.gov/pubmed/22301477.
  7. Della Negra M, De Carvalho AP, De Aquino MZ, et al. Long-term efficacy and safety of tenofovir disoproxil fumarate in HIV-1-infected adolescents failing antiretroviral therapy: the final results of study GS-US-104-0321. Pediatr Infect Dis J. 2015;34(4):398-405. Available at http://www.ncbi.nlm.nih.gov/pubmed/25599284.
  8. Riordan A, Judd A, Boyd K, et al. Tenofovir use in human immunodeficiency virus-1-infected children in the United Kingdom and Ireland. Pediatr Infect Dis J. 2009;28(3):204-209. Available at http://www.ncbi.nlm.nih.gov/pubmed/19209091.
  9. Baheti G, Kiser JJ, Havens PL, Fletcher CV. Plasma and intracellular population pharmacokinetic analysis of tenofovir in HIV-1-infected patients. Antimicrob Agents Chemother. 2011;55(11):5294-5299. Available at http://www.ncbi.nlm.nih.gov/pubmed/21896913.
  10. Baheti G, King JR, Acosta EP, Fletcher CV. Age-related differences in plasma and intracellular tenofovir concentrations in HIV-1-infected children, adolescents and adults. AIDS. 2013;27(2):221-225. Available at http://www.ncbi.nlm.nih.gov/pubmed/23032419.
  11. Hazra R, Gafni RI, Maldarelli F, et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infection. Pediatrics. 2005;116(6):e846-854. Available at http://www.ncbi.nlm.nih.gov/pubmed/16291735.
  12. Kiser JJ, Fletcher CV, Flynn PM, et al. Pharmacokinetics of antiretroviral regimens containing tenofovir disoproxil fumarate and atazanavir-ritonavir in adolescents and young adults with human immunodeficiency virus infection. Antimicrob Agents Chemother. 2008;52(2):631-637. Available at http://www.ncbi.nlm.nih.gov/pubmed/18025112.
  13. Stellbrink HJ, Orkin C, Arribas JR, et al. Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis. 2010;51(8):963-972. Available at http://www.ncbi.nlm.nih.gov/pubmed/20828304.
  14. McComsey GA, Kitch D, Daar ES, et al. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis. 2011;203(12):1791-1801. Available at http://www.ncbi.nlm.nih.gov/pubmed/21606537.
  15. Gafni RI, Hazra R, Reynolds JC, et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children. Pediatrics. 2006;118(3):e711-718. Available at http://www.ncbi.nlm.nih.gov/pubmed/16923923.
  16. Purdy JB, Gafni RI, Reynolds JC, Zeichner S, Hazra R. Decreased bone mineral density with off-label use of tenofovir in children and adolescents infected with human immunodeficiency virus. J Pediatr. 2008;152(4):582-584. Available at http://www.ncbi.nlm.nih.gov/pubmed/18346519.
  17. Aurpibul L, Puthanakit T. Review of tenofovir use in HIV-infected children. Pediatr Infect Dis J. 2015;34(4):383-391. Available at http://www.ncbi.nlm.nih.gov/pubmed/25247583.
  18. Havens PL, Kiser JJ, Stephensen CB, et al. Association of higher plasma vitamin D binding protein and lower free calcitriol levels with tenofovir disoproxil fumarate use and plasma and intracellular tenofovir pharmacokinetics: cause of a functional vitamin D deficiency? Antimicrob Agents Chemother. 2013;57(11):5619-5628. Available at http://www.ncbi.nlm.nih.gov/pubmed/24002093.
  19. Overton ET, Chan ES, Brown TT, et al. Vitamin D and Calcium Attenuate Bone Loss With Antiretroviral Therapy Initiation: A Randomized Trial. Ann Intern Med. 2015;162(12):815-824. Available at http://www.ncbi.nlm.nih.gov/pubmed/26075752.
  20. Havens PL, Stephensen CB, Hazra R, et al. Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial. Clin Infect Dis. 2012;54(7):1013-1025. Available at http://www.ncbi.nlm.nih.gov/pubmed/22267714.
  21. DiMeglio LA, Wang J, Siberry GK, et al. Bone mineral density in children and adolescents with perinatal HIV infection. AIDS. 2013;27(2):211-220. Available at http://www.ncbi.nlm.nih.gov/pubmed/23032412.
  22. Yin MT, Lund E, Shah J, et al. Lower peak bone mass and abnormal trabecular and cortical microarchitecture in young men infected with HIV early in life. AIDS. 2014;28(3):345-353. Available at http://www.ncbi.nlm.nih.gov/pubmed/24072196.
  23. 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. 2010;51(5):496-505. Available at http://www.ncbi.nlm.nih.gov/pubmed/20673002.
  24. Hall AM. Update on tenofovir toxicity in the kidney. Pediatr Nephrol. 2013;28(7):1011-1023. Available at http://www.ncbi.nlm.nih.gov/pubmed/22878694.
  25. 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. 2009;28(7):619-625. Available at http://www.ncbi.nlm.nih.gov/pubmed/19561425.
  26. Wood SM, Shah SS, Steenhoff AP, Meyers KE, Kaplan BS, Rutstein RM. Tenofovir-associated nephrotoxicity in two HIV-infected adolescent males. AIDS Patient Care STDS. 2009;23(1):1-4. Available at http://www.ncbi.nlm.nih.gov/pubmed/19183077.
  27. Hussain S, Khayat A, Tolaymat A, Rathore MH. Nephrotoxicity in a child with perinatal HIV on tenofovir, didanosine and lopinavir/ritonavir. Pediatr Nephrol. 2006;21(7):1034-1036. Available at http://www.ncbi.nlm.nih.gov/pubmed/16773419.
  28. Lucey JM, Hsu P, Ziegler JB. Tenofovir-related Fanconi's syndrome and osteomalacia in a teenager with HIV. BMJ Case Reports. 2013;2013. Available at http://www.ncbi.nlm.nih.gov/pubmed/23843401.
  29. Papaleo A, Warszawski J, Salomon R, et al. Increased beta-2 microglobulinuria in human immunodeficiency virus-1-infected children and adolescents treated with tenofovir. Pediatr Infect Dis J. 2007;26(10):949-951. Available at http://www.ncbi.nlm.nih.gov/pubmed/17901802.
  30. Soler-Palacin P, Melendo S, Noguera-Julian A, et al. Prospective study of renal function in HIV-infected pediatric patients receiving tenofovir-containing HAART regimens. AIDS. 2011;25(2):171-176. Available at http://www.ncbi.nlm.nih.gov/pubmed/21076275.
  31. Purswani M, Patel K, Kopp JB, et al. Tenofovir treatment duration predicts proteinuria in a multiethnic United States Cohort of children and adolescents with perinatal HIV-1 infection. Pediatr Infect Dis J. 2013;32(5):495-500. Available at http://www.ncbi.nlm.nih.gov/pubmed/23249917.
  32. Sise ME, Hirsch JS, Canetta PA, Herlitz L, Mohan S. Nonalbumin proteinuria predominates in biopsy-proven tenofovir nephrotoxicity. AIDS. 2015;29(8):941-946. Available at http://www.ncbi.nlm.nih.gov/pubmed/25784440.
  33. Samarawickrama A, Cai M, Smith ER, et al. Simultaneous measurement of urinary albumin and total protein may facilitate decision-making in HIV-infected patients with proteinuria. HIV Med. 2012;13(9):526-532. Available at http://www.ncbi.nlm.nih.gov/pubmed/22413854.

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