Pediatric HIV Infection: 
Drug Product 
Development for 
Treatment 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
 
March 2019 
Clinical/Medical 
   
Pediatric HIV Infection: 
Drug Product 
Development for 
Treatment 
Guidance for Industry
 
 
 
Additional copies are available from: 
 
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Center for Drug Evaluation and Research 
Food and Drug Administration 
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https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
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https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
   
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
 
March 2019 
Clinical/Medical 
 
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  DRUG PRODUCT DEVELOPMENT CONSIDERATIONS ...................................... 2 
  Contains Nonbinding Recommendations 
Pediatric HIV Infection:  
Drug Product Development for Treatment  
Guidance for Industry1 
 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.   
 
 
 
I.  INTRODUCTION    
 
The purpose of this guidance is to provide general recommendations on the development of 
antiretroviral (ARV) drug products2 for the treatment of human immunodeficiency virus (HIV) 
infection in pediatric (birth to younger than 18 years of age) patients. This guidance is intended 
to help sponsors understand when it is appropriate to initiate pediatric formulation development 
and to begin pediatric studies.  
 
This guidance clarifies FDAs current thinking on critical aspects of the development of pediatric 
HIV drug products intended for global use. The guidance for industry Human Immunodeficiency 
Virus-1 Infection: Developing Antiretroviral Drugs for Treatment (November 2015) addresses 
more broadly the development of ARV drug products for the treatment of HIV infection.3 
 
This guidance does not address the full scope of considerations in the development program and 
clinical trial designs for ARV drug products to support an indication for the treatment of HIV-1 
infection in adult or pediatric patients.4  
 
                                                 
1 This guidance has been prepared by the Division of Antiviral Products in the Center for Drug Evaluation and 
Research, in cooperation with the Center for Biologics Evaluation and Research, at the Food and Drug 
Administration. 
 
2 For the purposes of this guidance, all references to drug products include both human drugs and biological 
products unless otherwise specified. The sponsor should discuss individual product differences with the Division of 
Antiviral Products during product development. 
 
3 We update guidances periodically. To make sure you have the most recent version of a guidance, check the FDA 
guidance web page at https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.   
 
4 See the guidance for industry Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for 
Treatment and the draft guidance for industry General Clinical Pharmacology Considerations for Pediatric Studies 
for Drugs and Biological Products (December 2014). With respect to the latter, when final, this guidance will 
represent the FDAs current thinking on this topic. For the most recent version of a guidance, check the FDA 
guidance web page at https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.  
  1  Contains Nonbinding Recommendations 
In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required.  
 
 
II.  BACKGROUND 
 
HIV infection is a chronic viral infection that, when untreated, causes a progressive destruction 
of the immune system resulting in acquired immunodeficiency syndrome (AIDS). Global data 
from the Joint United Nations Programme on HIV/AIDS (UNAIDS) indicate that approximately 
2.1 million children (defined by UNAIDS as younger than 15 years of age) are living with HIV, 
of whom only 43 percent have received ARV therapy.5 Treatment of HIV consists of a 
combination of ARV drug products, typically three drug products from at least two classes.  
 
The goal of treatment is to maintain suppression of plasma HIV ribonucleic acid (RNA) levels 
below the level of detection by sensitive HIV-RNA assays (less than the lower limit of 
quantification, target not detected). Because the course of HIV infection and the effects of ARV 
drug products are considered sufficiently similar in pediatric and adult patients, pediatric efficacy 
of ARV drug products is generally extrapolated from adult trials based on bridging 
pharmacokinetics.6 In addition to pharmacokinetic data in children, safety and HIV-RNA (viral 
load) data to assess antiviral activity are collected during the pediatric studies.7       
 
 
III.  DRUG PRODUCT DEVELOPMENT CONSIDERATIONS 
 
Following are the major considerations for sponsors developing pediatric HIV drug products 
intended for global use: 
 
  Because dosing recommendations for ARV drug products have consistently been the 
same for adults and adolescents (for the purposes of this guidance, 12 to younger than 18 
years of age),8 the sponsor should include adolescents in the initial phase 3 (efficacy) 
clinical trials along with adults, or the sponsor should conduct a separate adolescent study 
in parallel with the adult phase 3 clinical trials. If adolescents are enrolled in an adult 
                                                 
5 UNAIDS, 2018, Fact SheetLatest Statistics on the Status of the AIDS Epidemics, UNAIDS.org, 
http://www.unaids.org/en/resources/fact-sheet.  
 
6 See the draft guidance for industry General Clinical Pharmacology Considerations for Pediatric Studies for Drugs 
and Biological Products. When final, this guidance will represent the FDAs current thinking on this topic. 
 
7 See the guidance for industry Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for 
Treatment. 
 
8 See the guidance for industry Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for 
Treatment. 
 
  2  Contains Nonbinding Recommendations 
phase 3 clinical trial, the sponsor should include them in the primary endpoint analysis. 
Differences between adolescents and adults, such as lower adherence rates, are not 
expected to affect clinical trial outcomes because the proportion of adolescents enrolled is 
expected to be comparatively small. The sponsor should also analyze the adolescent and 
the adult populations separately to help evaluate the consequences of possible differences 
in behaviors.  
 
  The sponsor should begin pediatric formulation development as soon as the adult dose is 
selected based on results from the phase 2 trial(s). 
 
  For the nonadolescent pediatric population (for the purposes of this guidance, 4 weeks to 
younger than 12 years of age),9 the sponsor should enroll cohorts within clinical studies 
in parallel rather than in series, unless a drug product has a specific safety or drug 
disposition factor that warrants a different approach. The sponsor can use 
pharmacokinetic modeling approaches based on the adult and the adolescent data for 
initial dose selection to initiate parallel enrollment of cohorts across the different weight 
groups in the nonadolescent pediatric population.10  
 
  The sponsor should enroll neonates (birth to younger than 4 weeks of age) separately 
upon reviewing the pharmacokinetic data and establishing the dose(s) for the older 
pediatric cohorts. 
  The sponsor should base cohort enrollment and dose selections during the nonadolescent 
pediatric clinical studies on weight rather than age. The selected weight bands should 
align with the weight bands predefined by the World Health Organization (WHO).11 
 
  When the sponsor has already established dosing regimens in pediatric patients using a 
previously approved formulation, approval of a new pediatric formulation (e.g., granules 
instead of solution) can be supported by a relative bioavailability study in adults that 
shows that the bioavailability of the two formulations is comparable. If bioavailability in 
adults is not comparable, the sponsor can use one or more of the following to support 
approval of the new pediatric formulation: dose adjustments, scientific rationale 
supporting the acceptability of the difference in bioavailability, or an additional clinical 
trial. Alternatively, the sponsor can develop different formulations.  
 
                                                 
9 There may be circumstances in which evaluating ARV drug products for treatment in children younger than 4 
weeks of age is appropriate and should be discussed with the Division of Antiviral Products. 
 
10 See the draft guidance for industry General Clinical Pharmacology Considerations for Pediatric Studies for 
Drugs and Biological Products. When final, this guidance will represent the FDAs current thinking on this topic. 
 
11 World Health Organization (WHO), 2016, Annex 11: Doses of Recommended Antiretroviral Drugs. In: WHO, 
Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: 
Recommendations for a Public Health Approach, Second Edition, France: WHO, 388395. Available at 
http://www.who.int/hiv/pub/arv/annexes-5Sep2016.pdf?ua=1.  
  3  Contains Nonbinding Recommendations 
  The FDA encourages sponsors to have early discussions with the WHO, 
nongovernmental organizations, the FDA, and others regarding pediatric plans to 
facilitate the development of drug products to meet the needs of pediatric patients (e.g., 
selection of formulation, strength and dosage of a drug product). 
  4