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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

What to Start

What Not to Start: Regimens Not Recommended for Initial Therapy of Antiretroviral-Naive Children

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

Many additional antiretroviral (ARV) agents and combinations are available; some are not recommended for initial therapy, although they may be used in treatment-experienced children. This section describes ARV drugs and drug combinations that are not recommended or for which data are insufficient to recommend use for initial therapy in ARV-naive children.

Not Recommended

These include drugs and drug combinations that are not recommended for initial therapy in ARV-naive children because of inferior virologic response, potential serious safety concerns (including potentially overlapping toxicities), or pharmacologic antagonism. These drugs and drug combinations are listed in Table 10.

Insufficient Data to Recommend

Drugs and drug combinations approved for use in adults that have insufficient, limited, and/or no pharmacokinetic (PK) or safety data for children cannot be recommended as initial therapy in children. However, these drugs and drug combinations may be appropriate for consideration in management of treatment-experienced children (see Management of Children Receiving Antiretroviral Therapy). These drugs are also listed in Table 10.

Antiretroviral Drugs and Combinations Not Recommended for Initial Therapy

In addition to the regimens listed below, several ARVs—including unboosted atazanavir in adolescents aged <13 years, nelfinavir and tenofovir disoproxil fumarate (tenofovir) in children aged <2 years, unboosted darunavir, once-daily dosing of lopinavir/ritonavir, and full-dose ritonavir—are not recommended for use as initial therapy.

Enfuvirtide-Based Regimens

Enfuvirtide, a fusion inhibitor, is Food and Drug Administration (FDA)-approved for use in combination with other ARV drugs to treat children aged ≥6 years who have evidence of HIV replication despite ongoing combination antiretroviral therapy (cART) (i.e., treatment-experienced children on non-suppressive regimens). Enfuvirtide is not recommended as initial therapy because the drug must be administered subcutaneously twice daily and is associated with a high incidence of local injection site reactions (98%).

Fosamprenavir Without Ritonavir Boosting

Fosamprenavir without ritonavir boosting has been studied in children aged ≥2 years but is not recommended because the large volume of fosamprenavir oral suspension necessary to administer in the absence of ritonavir boosting is prohibitive. In addition, low levels of exposure may result in selection of resistance mutations that are associated with darunavir resistance.

Indinavir-Based Regimens

Although adequate virologic and immunologic responses have been observed with indinavir-based regimens in adults, the drug is not available in a liquid formulation and high rates of hematuria, sterile leukocyturia, and nephrolithiasis have been reported in pediatric patients using indinavir.1-4 The incidence of hematuria and nephrolithiasis with indinavir therapy may be higher in children than adults.1,4 Therefore, indinavir alone or with ritonavir boosting is not recommended as initial therapy in children.

Regimens Containing Only Nucleoside Reverse Transcriptase Inhibitors

In adult trials, regimens containing only nucleoside reverse transcriptase inhibitors (NRTIs) have shown less potent virologic activity when compared with more potent non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based regimens. These include studies of zidovudine plus abacavir plus lamivudine, stavudine plus didanosine plus lamivudine, stavudine plus lamivudine plus abacavir, didanosine plus stavudine plus abacavir, tenofovir plus abacavir plus lamivudine, and tenofovir plus didanosine plus lamivudine.5,6 Data on the efficacy of triple-NRTI regimens for treatment of ARV-naive children are limited; in small observational studies, response rates of 47% to 50% have been reported.7,8 In a study of the triple-NRTI regimen abacavir, lamivudine, and zidovudine in previously treated children, the combination showed evidence of only modest viral suppression, with only 10% of 102 children maintaining a viral load of <400 copies/mL at 48 weeks of treatment.9 Therefore, regimens containing only NRTIs are not recommended. A possible exception to this recommendation is the treatment of young children (aged <3 years) with concomitant HIV infection and tuberculosis for whom a nevirapine-based regimen is not acceptable. For these children, where treatment choices are limited, the World Health Organization recommends the use of a triple-NRTI regimen.10

Regimens Containing Three Drug Classes

Data are insufficient to recommend initial regimens containing agents from three drug classes (e.g., NRTI plus NNRTI plus PI). Although studies containing three classes of drugs have demonstrated these regimens to be safe and effective in previously treated HIV-infected children and adolescents, these regimens have not been studied as initial therapy in treatment-naive children and adolescents and have the potential for inducing resistance to three drug classes, which could severely limit future treatment options.11-15 Ongoing studies, however, are investigating three drug classes as treatment in HIV-infected neonates.

Regimens Containing Three NRTIs and an NNRTI

Data are currently insufficient to recommend a regimen of three NRTIs plus an NNRTI in young infants. A recent review of nine cohorts from 13 European countries suggested superior responses to this four-drug regimen when compared to boosted PI or three-drug NRTI regimens.16 There has been speculation that poor tolerance and adherence to a PI-based regimen may account for differences. The ARROW trial conducted in Uganda and Zimbabwe randomized 1,206 children (median age 6 years) to a standard NNRTI-based three-drug regimen versus a four-drug regimen (three NRTIs and an NNRTI). After a 36-week induction period, the children on the four-drug regimen were continued on a dual NRTI plus NNRTI or an all NRTI-based regimen. Although early benefits in CD4 T lymphocyte improvement and virologic control were observed in the four-drug arm, these benefits were not sustained after de-intensification to the three-NRTI arm.17 Furthermore, after a median of 3.7 years on therapy, children in the initial four-drug arm who changed to an all NRTI-based regimen had significantly poorer virologic control.18 Based on demonstrated benefits of recommended three-drug regimens and lack of additional efficacy data on the four-drug regimen, the Panel does not currently recommend this regimen.

Saquinavir with Low-Dose Ritonavir

A saquinavir/ritonavir-based regimen compared with a lopinavir/ritonavir-based regimen demonstrated comparable virologic and immunologic outcomes when used as initial therapy in treatment-naive adults.19 However, saquinavir is not recommended for initial therapy in children because the agent is not available in a pediatric formulation, and dosing and outcome data on saquinavir use in children are limited.

Stavudine in Combination with Didanosine

The dual-NRTI combination of stavudine/didanosine is not recommended for use as initial therapy because of greater toxicity when used in combination. In small pediatric studies, stavudine/didanosine demonstrated virologic efficacy and was well tolerated.20-22 However, in studies in adults, stavudine plus didanosine-based combination regimens were associated with greater rates of neurotoxicity, pancreatitis, hyperlactatemia and lactic acidosis, and lipodystrophy than therapies based on zidovudine plus lamivudine.23,24 In addition, cases of fatal and non-fatal lactic acidosis with pancreatitis/hepatic steatosis have been reported in women receiving this combination during pregnancy.25,26

Tipranavir-Based Regimens

This agent has been studied in treatment-experienced children and adults. Tipranavir is a PI licensed for use in children aged ≥2 years. Tipranavir-based regimens are not recommended because higher doses of ritonavir to boost tipranavir must be used and rare, but serious, cases of intracranial hemorrhage have been reported.

Antiretroviral Drugs and Combinations with Data Insufficient to Recommend for Initial Therapy in Children

A number of ARV drugs and drug regimens are not recommended for initial therapy in ARV-naive children or for specific age groups because of insufficient pediatric data. These include the dual-NRTI backbone combinations abacavir/didanosine, abacavir/tenofovir, and didanosine/tenofovir. In addition, several new agents appear promising for use in adults but do not have sufficient pediatric PK and safety data to recommend their use as components of an initial therapeutic regimen in children. These agents include maraviroc (CCR5 antagonist), elvitegravir (integrase strand transfer inhibitor [INSTI]), and etravirine and rilpivirine (both NNRTIs). In addition, some dosing schedules may not be recommended in certain age groups based on insufficient data. As new data become available, these agents may be considered as recommended agents or regimens. These are summarized below and also listed in Table 10.

Darunavir with Low-Dose Ritonavir when Administered Once Daily (for Children Aged ≥3 to 12 Years)

Data are limited on PK of once-daily darunavir/ritonavir in young children. While modeling studies identified a once-daily dosing regimen now approved by FDA, the Panel is concerned about the lack of efficacy data for individuals aged ≥3 to <12 years treated with once-daily darunavir/ritonavir. Therefore once-daily dosing for initial therapy is not recommended in this age group. For children aged ≥3 to <12 years, twice-daily darunavir boosted with ritonavir is an alternate PI regimen. For older children who have undetectable viral load on twice-daily therapy with darunavir/ritonavir, practitioners can consider changing to once-daily treatment to enhance ease of use and support adherence if no darunavir-associated resistance mutations are present.

Dolutegravir for Children Aged <12 Years

Dolutegravir is an INSTI that has recently been approved by FDA for use in children 12 years and older and weighing at least 40 kg. At this time there is no information about its use in children aged <12 years, but a clinical trial in treatment-experienced children aged <12 years is under way.

Efavirenz for Children Aged ≥3 Months to 3 Years

Efavirenz is FDA-approved for use in children as young as 3 months who weigh at least 3.5 kg. Concerns regarding variable PK of the drug in the very young have resulted in a recommendation to not use efavirenz in children younger than 3 years at this time (see Efavirenz in Appendix A: Pediatric Antiretroviral Drug Information). Based on the recommended efavirenz dosage for children younger than 3 years, the IMPAACT P1070 study estimated the variability in area under the curve (AUC) for efavirenz based on polymorphisms in cytochrome P (CYP) 2B6 516. The findings suggest that 38% of extensive metabolizers would have subtherapeutic AUCs and 67% of poor metabolizers would have excessive AUCs based on recommended dosing.27 Thus, should efavirenz be considered, CYP2B6 genotyping that predicts efavirenz metabolic rate should be performed, if available. Therapeutic drug monitoring can also be considered.

Elvitegravir-Based Regimens

Elvitegravir is an INSTI available as a tablet and as a fixed-dose combination tablet containing elvitegravir/cobicistat/emtricitabine/tenofovir. It is FDA-approved for use as cART in HIV-1-infected cART-naive adults. Elvitegravir tablets must be taken in combination with a low-dose, ritonavir-boosted PI. Neither formulation is FDA-approved for use in children aged <18 years. A small study (14 participants) of the fixed-dose combination tablet containing elvitegravir/cobicistat/emtricitabine/tenofovir in treatment-naive children and adolescents, aged 12 to 17 years, has reported PK, tolerability, and virologic efficacy at 24 weeks. The therapy was well tolerated and all subjects taking the cART at 24 weeks had viral loads less than 400 copies/mL; 11 had viral loads less than 50 copies/mL. Steady state exposure was similar to that observed in adults, as were small increases in serum creatinine without evidence of nephrotoxicity. These data suggest that elvitegravir/cobicistat/emtricitabine/tenofovir is efficacious in children and adolescents aged 12 to 18 years, but evidence is insufficient for this regimen to be recommended as initial therapy for treatment-naive children and adolescents in this age group.

Etravirine-Based Regimens

Etravirine is an NNRTI that has been studied in treatment-experienced children 6 years and older.28,29 It is associated with multiple interactions with other ARVs, including tipranavir/ritonavir, fosamprenavir/ritonavir, atazanavir/ritonavir, and unboosted PIs, and must be administered twice daily. Studies in treatment-experienced younger children are under way. It is unlikely that etravirine will be studied in treatment-naive children.

Rilpivirine-Based Regimens

Rilpivirine is currently available both as a single-agent formulation and a once-daily, fixed-dose combination tablet containing emtricitabine and tenofovir. A recent study of rilpivirine, 25 mg daily in combination with two NRTIs in treatment-naive adolescents aged 12 to 18 years, demonstrated that the regimen was well-tolerated over 24 weeks. Among adolescents with baseline viral loads ≤100,000 copies/mL, 86% had a virologic response.30 In adult studies, reduced viral suppression was observed in patients with initial HIV RNA >100,000 copies/mL; similar reduced response was also observed in the pediatric study. In adults, rilpivirine is recommended only if HIV RNA is ≤100,000 copies/mL; it is not recommended as initial therapy for treatment-naive children and adolescents, and if used in older children and adolescents (aged >12 years) it should only be used if HIV RNA is <100,000 copies/mL.

Maraviroc-Based Regimens

Maraviroc is an entry inhibitor that has been used infrequently in children. A dose-finding study in treatment-experienced children aged 2 to 18 years is enrolling patients in four age cohorts using both liquid and tablet formulations. Initial dose is based on body surface area and scaled from recommended adult dosage. Dose adjustments were required in patients not receiving a potent CYP450 3A4 inhibitor or inducer.31 The drug has multiple drug interactions and must be administered twice daily. In addition, tropism assays must be performed prior to use to ensure the presence of only CCR5-tropic virus.

Antiretroviral Drug Regimens that Should Never Be Recommended

Several ARV drugs and drug regimens should never be recommended for use in therapy of children or adults. These are summarized in Table 11. Clinicians should be aware of the components of fixed-drug combinations so that patients do not inadvertently receive a double dose of a drug contained in such a combination.


Table 10. ART Regimens or Components Not Recommended for Initial Treatment of HIV Infection in Children
Regimen or ARV Component
Rationale for Being Not Recommended
Unboosted ATV-containing regimens in children aged <13 years and/or weight <39 kg
Reduced exposure
DRV-based regimens once daily in children ≥3 to 12 years Insufficient data to recommend
Unboosted DRV 
Use without ritonavir has not been studied.
Dual (full-dose) PI regimens Insufficient data to recommend
Dual NRTI combination of ABC plus ddI Insufficient data to recommend
Dual NRTI combination of ABC plus TDF Insufficient data to recommend
Dual NRTI combination of d4T plus ddI
Significant toxicities
Dual NRTI combination of TDF plus ddI Increase in concentrations; high rate of virologic failure
EFV-based regimens for children aged <3 years Appropriate dose not determined
T20-containing regimens Insufficient data to recommend
Injectable preparation
ETR-based regimens
Insufficient data to recommend
EVG-based regimens Insufficient data to recommend
FPV without RTV boosting
Reduced exposure
Medication burden
IDV-based regimens Renal toxicities
LPV/r dosed once daily Reduced drug exposure
MVC-based regimens   
Insufficient data to recommend
NFV-containing regimens for children aged <2 years
Appropriate dose not determined
Regimens containing only NRTIs Inferior virologic efficacy
Regimens containing three drug classes Insufficient data to recommend
Full-dose RTV or use of RTV as the sole PI GI intolerance
Metabolic toxicity
Regimens containing three NRTIs and an NNRTI
Insufficient data to recommend
RPV-based regimens Insufficient data to recommend
SQV-based regimens
Limited dosing and outcome data burden
TDF-containing regimens in children aged <2 years Potential bone toxicity
Appropriate dose has yet to be determined.
TPV-based regimens Increased dose of RTV for boosting
Reported cases of intracranial hemorrhage
Key to Abbreviations: ABC = abacavir; ARV = antiretroviral; ATV = atazanavir; d4T = stavudine; ddI = didanosine; DRV = darunavir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; FPV = fosamprenavir; GI = gastrointestinal; IDV = indinavir; LPV/r = ritonavir-boosted lopinavir; MVC = maraviroc; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; T20 = enfuvirtide; TDF = tenofovir disoproxil fumarate; TPV = tipranavir

Table 11. ART Regimens or Components that Should Never Be Recommended for Treatment of HIV Infection in Children
ART Regimens Never Recommended for Children
Regimen Rationale Exceptions
One ARV drug alone (monotherapy)
  • Rapid development of resistance
  • Inferior antiviral activity compared with combination including ≥3 ARV drugs
  • Monotherapy “holding” regimens associated with more rapid CD4 decline compared to non-suppressive cART
  • HIV-exposed infants (with negative viral testing) during 6-week period of prophylaxis to prevent perinatal transmission of HIV
Two NRTIs alone
  • Rapid development of resistance
  • Inferior antiviral activity compared with combination including ≥3 ARV drugs
  • Not recommended for initial therapy
  • For patients currently on 2 NRTIs alone who achieve virologic goals, some clinicians may opt to continue this treatment.
TDF plus ABC plus (3TC or FTC) as a triple-NRTI regimen
  • High rate of early viral failure when this triple-NRTI regimen was used as initial therapy in treatment-naive adults.
  • No exceptions
TDF plus ddI plus (3TC or FTC) as a triple-NRTI regimen
  • High rate of early viral failure when this triple-NRTI regimen was used as initial therapy in treatment-naive adults.
  • No exceptions
ARV Components Never Recommended as Part of an ARV Regimen for Children
Regimen Rationale Exceptions
ATV plus IDV
  • Potential additive hyperbilirubinemia
  • No exceptions
Dual-NNRTI Combinations
  • Enhanced toxicity
  • No exceptions
Dual-NRTI Combinations:
  • 3TC plus FTC  
 
  • Similar resistance profile and no additive benefit
  • No exceptions
  • d4T plus ZDV 
  • Antagonistic effect on HIV
  • No exceptions
EFV in first trimester of pregnancy or for sexually active adolescent girls of childbearing potential when reliable contraception cannot be ensured
  • Potential for teratogenicity
  • When no other ARV option is available and potential benefits outweigh risks
NVP as initial therapy in adolescent girls with CD4 count >250 cells/mm3 or adolescent boys with CD4 count >400 cells/mm3
  • Increased incidence of symptomatic (including serious and potentially fatal) hepatic events in these patient groups 
  • Only if benefit clearly outweighs risk
Unboosted SQV, DRV, or TPV
  • Poor oral bioavailability
  • Inferior virologic activity compared with other PIs
  • No exceptions
Key to Abbreviations: 3TC = lamivudine; ABC = abacavir; ARV = antiretroviral; ATV = atazanavir; cART = combination antiretroviral therapy; CD4 = CD4 T lymphocyte; d4T = stavudine; ddI = didanosine; DRV = darunavir; EFV = efavirenz; FTC = emtricitabine; IDV = indinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; SQV = saquinavir; TDF = tenofovir disoproxil fumarate; TPV = tipranavir; ZDV = zidovudine

References

  1. Fraaij PL, Verweel G, van Rossum AM, Hartwig NG, Burger DM, de Groot R. Indinavir/low-dose ritonavir containing HAART in HIV-1 infected children has potent antiretroviral activity, but is associated with side effects and frequent discontinuation of treatment. Infection. 2007;35(3):186-189. Available at http://www.ncbi.nlm.nih.gov/pubmed/17565462.
  2. Jankelevich S, Mueller BU, Mackall CL, et al. Long-term virologic and immunologic responses in human immunodeficiency virus type 1-infected children treated with indinavir, zidovudine, and lamivudine. J Infect Dis. 2001;183(7):1116-1120. Available at http://www.ncbi.nlm.nih.gov/pubmed/11237839.
  3. van Rossum AM, Geelen SP, Hartwig NG, et al. Results of 2 years of treatment with protease-inhibitor--containing antiretroviral therapy in dutch children infected with human immunodeficiency virus type 1. Clin Infect Dis. 2002;34(7):1008-1016. Available at http://www.ncbi.nlm.nih.gov/pubmed/11880968.
  4. 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. 2002;110(2 Pt 1):e19. Available at http://www.ncbi.nlm.nih.gov/pubmed/12165618.
  5. Gerstoft J, Kirk O, Obel N, et al. Low efficacy and high frequency of adverse events in a randomized trial of the triple nucleoside regimen abacavir, stavudine and didanosine. AIDS. 2003;17(14):2045-2052. Available at http://www.ncbi.nlm.nih.gov/pubmed/14502007.
  6. van Leeuwen R, Katlama C, Murphy RL, et al. A randomized trial to study first-line combination therapy with or without a protease inhibitor in HIV-1-infected patients. AIDS. 2003;17(7):987-999. Available at http://www.ncbi.nlm.nih.gov/pubmed/12700448.
  7. Saavedra J, Mccoig C, Mallory M, et al. Clinical experience with triple nucleoside (NRTI) combination ZDV/3TC/abacavir (ABC) as initial therapy in HIV-infected children. Presented at: 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. 2001. Chicago, IL.
  8. Handforth J, Sharland M. Triple nucleoside reverse transcriptase inhibitor therapy in children. Paediatr Drugs. 2004;6(3):147-159. Available at http://www.ncbi.nlm.nih.gov/pubmed/15170362.
  9. Saez-Llorens X, Nelson RP, Jr., Emmanuel P, et al. A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. The CNAA3006 Study Team. Pediatrics. 2001;107(1):E4. Available at http://www.ncbi.nlm.nih.gov/pubmed/11134468.
  10. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. 2013. Available at http://www.who.int/hiv/pub/guidelines/arv2013/download/en/index.html. Accessed July 31, 2013.
  11. Spector SA, Hsia K, Yong FH, et al. Patterns of plasma human immunodeficiency virus type 1 RNA response to highly active antiretroviral therapy in infected children. J Infect Dis. 2000;182(6):1769-1773. Available at http://www.ncbi.nlm.nih.gov/pubmed/11069252.
  12. Starr SE, Fletcher CV, Spector SA, et al. Combination therapy with efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors in children infected with human immunodeficiency virus type 1. Pediatric AIDS Clinical Trials Group 382 Team. N Engl J Med. 1999;341(25):1874-1881. Available at http://www.ncbi.nlm.nih.gov/pubmed/10601506.
  13. Starr SE, Fletcher CV, Spector SA, et al. Efavirenz liquid formulation in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2002;21(7):659-663. Available at http://www.ncbi.nlm.nih.gov/pubmed/12237599.
  14. Wiznia A, Stanley K, Krogstad P, et al. Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV-infected children: week 24 results of a randomized controlled trial--PACTG 377. Pediatric AIDS Clinical Trials Group 377 Study Team. AIDS Res Hum Retroviruses. 2000;16(12):1113-1121. Available at http://www.ncbi.nlm.nih.gov/pubmed/10954886.
  15. Krogstad P, Lee S, Johnson G, et al. Nucleoside-analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir for pretreated children infected with human immunodeficiency virus type 1. Clin Infect Dis. 2002;34(7):991-1001. Available at http://www.ncbi.nlm.nih.gov/pubmed/11880966.
  16. Judd A, European P, Paediatric HIVCCsgiE. Early antiretroviral therapy in HIV-1-infected infants, 1996-2008: treatment response and duration of first-line regimens. AIDS. 2011;25(18):2279-2287. Available at http://www.ncbi.nlm.nih.gov/pubmed/21971357.
  17. Arrow Trial team, Kekitiinwa A, Cook A, et al. Routine versus clinically driven laboratory monitoring and first-line antiretroviral therapy strategies in African children with HIV (ARROW): a 5-year open-label randomised factorial trial. Lancet. 2013;381(9875):1391-1403. Available at http://www.ncbi.nlm.nih.gov/pubmed/23473847.
  18. Nahirya-Ntege P, Cook A, et al. Significant short-term benefits of 4-drug first line ART do not persist with 3-drug maintenance in 1206 HIV-infected African children; ART strategies in the 5-year ARROW trial. Presented at: 19th Conference on Retroviruses and Opportunistic Infections. 2013. Atlanta, GA.
  19. Walmsley S, Avihingsanon A, Slim J, et al. Gemini: a noninferiority study of saquinavir/ritonavir versus lopinavir/ritonavir as initial HIV-1 therapy in adults. J Acquir Immune Defic Syndr. 2009;50(4):367-374. Available at http://www.ncbi.nlm.nih.gov/pubmed/19214123.
  20. de Mendoza C, Ramos JT, Ciria L, et al. Efficacy and safety of stavudine plus didanosine in asymptomatic HIV-infected children with plasma HIV RNA below 50,000 copies per milliliter. HIV Clin Trials. 2002;3(1):9-16. Available at http://www.ncbi.nlm.nih.gov/pubmed/11819180.
  21. Kline MW, Van Dyke RB, Lindsey JC, et al. A randomized comparative trial of stavudine (d4T) versus zidovudine (ZDV, AZT) in children with human immunodeficiency virus infection. AIDS Clinical Trials Group 240 Team. Pediatrics. 1998;101(2):214-220. Available at http://www.ncbi.nlm.nih.gov/pubmed/9445494.
  22. Kline MW, Van Dyke RB, Lindsey JC, et al. Combination therapy with stavudine (d4T) plus didanosine (ddI) in children with human immunodeficiency virus infection. The Pediatric AIDS Clinical Trials Group 327 Team. Pediatrics. 1999;103(5):e62. Available at http://www.ncbi.nlm.nih.gov/pubmed/10224206.
  23. Blanco F, Garcia-Benayas T, Jose de la Cruz J, Gonzalez-Lahoz J, Soriano V. First-line therapy and mitochondrial damage: different nucleosides, different findings. HIV Clin Trials. 2003;4(1):11-19. Available at http://www.ncbi.nlm.nih.gov/pubmed/12577192.
  24. Shafer RW, Smeaton LM, Robbins GK, et al. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003;349(24):2304-2315. Available at http://www.ncbi.nlm.nih.gov/pubmed/14668456.
  25. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. 2011. Available at http://aidsinfo.nih.gov/contentfiles/PerinatalGL.pdf.
  26. Dieterich DT. Long-term complications of nucleoside reverse transcriptase inhibitor therapy. AIDS Read. 2003;13(4):176-184, 187. Available at http://www.ncbi.nlm.nih.gov/pubmed/12741368.
  27. Moore CB, Capparelli E, Samson P, Bwakura-Dangarembizi M, et al. CYP2B6 polymorphisms challenge generalized FDA efavirenz dosing guidelines in children < 3 years. Presented at: 20th Conference on Retroviruses and Opportunistic Infections. 2014. Boston, MA.
  28. Konigs C, Feiterna-Sperling C, Esposito S, et al. Pharmacokinetics and short-term safety and tolerability of etravirine in treatment-experienced HIV-1-infected children and adolescents. AIDS. 2012;26(4):447-455. Available at http://www.ncbi.nlm.nih.gov/pubmed/22156961.
  29. Tudor-Williams G, Cahn P, Chokephaibulkit K, et al. Etravirine in treatment-experienced, HIV-1-infected children and adolescents: 48-week safety, efficacy and resistance analysis of the phase II PIANO study. HIV Med. 2014. Available at http://www.ncbi.nlm.nih.gov/pubmed/24589294.
  30. Lombaard J, Bunupuradah T, et al. Safety and efficacy of a rilpivirine-based regimen in HIV-infected treatment-naive adolescents: Week 24 primary analysis of the PAINT phase II trial. Presented at: 6th International Workshop on HIV Pediatrics. 2014. Melbourne, Australia.
  31. Vourvahis M. Update from Study A4001031: maraviroc pharmacokinetics in CCR5-tropic HIV-1-infected children aged 2 to < 18 years. Presented at: 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention. 2013. Kuala Lumpur, Malaysia.

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