The paediatric pipeline 2017
Polly Clayden, HIV i-Base
Paediatric investigation plans (PIPs)  and paediatric study plans (PSPs) – required by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA)  respectively – will be under discussion for all compounds in early phases of development for adults by originator manufacturers (described in the previous section).
PIPs are compulsory for all new drugs and FDCs before the marketing authorisation application is submitted – usually at the end of phase 1 development. PSPs must be agreed on before filing a new drug application (NDA) – at the end of phase 2.
Both regulatory agencies offer incentives and/or penalties to ensure that any new drug that might benefit children must be studied in this population. The EMA enforces penalties for companies that do not provide a PIP as part of their application (or request a waiver), and gives patent extensions for completing the PIP. The FDA also extends six-month patent protection to companies that perform the requested paediatric studies – though companies are not required to do this.
Paediatric development can be waived for specific drugs or classes of drugs that are likely to be ineffective or unsafe in all or some paediatric age groups. A waiver can also be obtained for products that are intended for conditions that only occur in adults, or that do not represent a benefit over existing paediatric treatments. In some cases, studies can be deferred until after the adult studies have been conducted.
Manufacturers must include PK data for all age groups of children, efficacy, tolerability, and differences in side effects. They must have stability and palatability data for formulations and demonstrate that they are able to achieve PK targets associated with efficacy in adults.
Studies are conducted in children as soon as there are sufficient data from those in adults. Most paediatric development programmes take an age staggered approach, starting with the older cohorts of children and working in de-escalated age bands: 12 to less than 18 years; 6 to less than 12 years; 2 to less than six years; 6 months to less than 2 years and below six months. Data are required in the youngest age groups – down to new-borns – unless a regulatory waiver is obtained. As the youngest age group is last to be studied and approved there are considerable delays in availability of new drugs for this population.
The problems with the age-staggered approach that results in delays in approval and availability of new drugs, particularly in the youngest age group where options are lacking, have been much discussed. World Health Organisation (WHO) uses a weight band dosing approach and it would make sense to investigate weight band dosing in paediatric antiretroviral development from the beginning, optimising the use of PK data and modelling. The dolutegravir (DTG) development programme, IMPAACT P1093, will try to capture enough data to inform weight band dosing, with the dispersible tablet in the younger cohorts.
Moving away from the age-staggered approach in to weight bands could also make it possible to open multiple cohorts simultaneously, if formulations are available, which would speed up availability of new drugs for infants and children considerably.
It would be interesting to see if doses for younger children have changed dramatically from predicted milligrams per kilogram ones due to PK data from older cohorts.
If work on aligning age bands with WHO weight bands could be done as originator manufacturers conduct their paediatric development programmes, this would help generic manufacturers develop co-formulations and FDCs that allow dosing aligned with recommendations across the weight bands. It could help close the gap between when new drugs and regimens are available for adults and children.
|Compound||Sponsor||Formulation/s and dose||Status and comments|
|Nucleotide reverse transcriptase inhibitor and combinations|
|Emtricitabine/tenofovir alafenamide (F/TAF)||Gilead||Reduced strength, co-formulated tablets and non-solid formulation in development||Approved >12 years.
Phase 2/3 switch study in children and adolescents stable on FTC/TDF plus 3rd agent 6 to <18 years.
Study in infants and children 4 weeks to <6 years planned
|Elvitegravir, cobicistat, emtricitabine, tenofovir alfenamide (E/C/F/TAF)||Gilead||Reduced dose FDC tablets in development||Approved >12 years.
Phase 2/3 single arm, open label E/C/F/TAF treatment-naive children and adolescents 6 to <18 years.
Waiver <6 years.
|Rilpivirine (R)/F/TAF||Gilead/Janssen||Reduced strength FDC tablets||Approved >12 years.
Dependent on development of RPV and F/TAF. Waiver <2 years.
|Bictegravir (B)/F/TAF||Gilead||Reduced strength FDC tablets||12 to <18 years submitted to FDA. Switch study in stable children and adolescents 6 to <18 years. 4 weeks to <6 years planned.|
|Non-nucleoside reverse transcriptase inhibitors|
|Etravirine (ETR)||Janssen||Dispersible tablets 25 (scored), 100mg||Approved >6 years.
Phase 1/2 treatment-experienced infants and children 2 months to <6 years and treatment-naive 2 months to <2 years enrolling. Waiver <2 months.
|Rilpivirine (RPV)||Janssen||Tablet 25mgGranules 2.5mg/g||Approved >12 years with viral load < 100,000 copies/mL.
2 to <12 years planned.
|Doravirine||Merck||Single agent and FDC with TDF/3TC planned||Switch and treatment-naive studies planned. Waiver for <2 years FDC.|
|Integrase inhibitors and combinations|
|Raltegravir (RAL)||Merck||Granules for suspension 6mg/kg (100 mg sachet).
Chewable 25 and 100 mg tablets
|Approved for use in children >4 weeks. Studies underway in HIV infected and exposed infants <4 weeks.|
|E/C/F/TDF (Stribild)||Gilead||Reduced dose tablets in development||Studies underway in treatment-naive 12 to <18 years. 6 to <12 years planned. Waiver <6 years.|
See TAF above
|Gilead||Reduced dose tablets in development||Studies underway in treatment-naive 12 to <18 years. 6 to <12 years planned. Waiver <6 years.|
|Dolutegravir (DTG)||ViiV Healthcare||Dispersible 5 mg tablets in development.
10 mg and 25 mg tablets
|Approved for children and adolescents >6 years, weighing >30/15 kg FDA/EMA. Phase 1/2 study, 6 weeks to <18 years treatment-naive and -experienced children, ongoing.|
|DTG/ABC/3TC||ViiV||Reduced strength film coated and dispersible tablets||Approved for adolescents >12 years and >40 kg.
Dependent on ongoing studies confirming DTG dose in children and ability to establish appropriate dosing ratios for components.
Waiver <2 years.
|DTG/RPV||ViiV/Jansen||Reduced strength co-formulation||To be studied as maintenance regimen 6 to <years and virologically suppressed.
Waiver <6 years.
|DTG/3TC||ViiV||Reduced strength co-formulation||Waiver <2 years|
|Cabotegravir/RPV long acting (LA)||ViiV/Janssen||Age appropriate liquid formulation for induction
Intramuscular nanosuspension as for adults
|Treatment and prevention phase 1/2. Waiver <2 years (treatment) <12 years prevention. Deferral 2 to <18 years.|
|B/F/TAF||Gilead||Reduced strength FDCs||See TAF above|
|Cobicistat (COBI)||Gilead||75 mg tablets.
20 mg dispersible tablets for oral suspension
|Booster. Also part of E/C/F/TDF and E/C/F/TAF.|
|Atazanavir/cobicistat (ATV/c)||Gilead/BMS||Reduced strength and dispersible tablets planned||Phase 2/3 treatment experienced children.
3 months to <18 years (ATV/c). 3 to <18 years (DRV/c)
|Darunavir/cobicistat (DRV/c)||Gilead/Janssen||Reduced strength and dispersible tablets planned||Phase 2/3 treatment experienced children.
3 months to <18 years (ATV/c). 3 to <18 years (DRV/c).
|Darunavir/cobicistat/ emtricitabine/tenofovir alafenamide
|Gilead/Janssen||Reduced strength and dispersible tablets planned||Phase 3. 6 to < 18 years.
6 years of age or weighing less than 25 kg
|HIV Neutralising Monoclonal Antibody|
|VRC01||IMPAACT||Single 20 or 40 mg/kg subcutaneous dose within 72 hours of birth||Phase 1. At risk infants >36 weeks of gestation or >2 kg at birth.|
Nucleotide reverse transcriptase inhibitor
TAF is considered a priority for future generic FDCs for children. Early data in adults suggests that it might have a better safety profile than TDF. This has yet to be confirmed in children. TAF also has a low milligram adult dose: 25 mg without a boosting agent and 10 mg boosted.
For children TAF might be an alternative to abacavir. It could help to harmonise paediatric and adult ART regimens, particularly if it could be co-formulated with DTG and 3TC or FTC.
The originator company Gilead Sciences is developing a co-formulation with FTC (F/TAF) and TAF-containing FDCs of elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF (E/C/F/TAF) and bictegravir (B/F/TAF). In collaboration with Janssen there is also an FDC with rilpivirine (R/F/TAF).
Adolescents aged 12 to less than 18 years switch their current two nucleoside reverse transcriptase inhibitor (NRTI) containing regimen to F/TAF (while continuing on their third antiretroviral agent) for 96 weeks. Children aged 6 to less than 12 are randomised to receive either F/TAF or FTC/TDF while continuing their third antiretroviral agent through 96 weeks.
A study in infants and children aged 4 weeks to 6 years is planned. Reduced strength tablets and a non-solid formulation are in development. As with the paediatric formulation of TDF, the taste of TAF is bitter and will need masking. This is particularly tricky and important for dispersible forms for children who cannot swallow tablets.
E/C/F/TAF is also approved for adolescents 12 years and above at the adult doses: 150/150/200/10mg.
E/C/F/TAF is being investigated in phase 2/3, single arm, open label studies treatment-naive adolescents and virologically suppressed children and adolescents aged 6 to less than18 years. There is a waiver for children below six years old. [7, 8, 9]
In 12 to less than 18 year olds receiving E/C/F/TAF, steady-state PK parameters of EVG, COBI, FTC, TAF and its metabolite tenofovir (TFV) were compared to adult exposures.  The study found TAF (as well as TFV, EVG, COBI, and FTC) PK parameters in adolescents to be consistent with those associated with safety and efficacy in adults.
In 6 to less than 12 year olds, at week 24, plasma PK of EVG, COBI, FTC, TAF and TFV were modestly higher (20-80%) than in adults, but were within safe and efficacious adult ranges. 
E/C/F/TAF was generally well tolerated in both studies with a favourable renal and bone safety profile and participants remained virologically suppressed.
An NDA for the adult formulation of B/F/TAF 50/200/25 mg has recently been submitted to the FDA.  Gilead plans to submit a marketing authorisation to the EMA later this year.
Formulation and trial design for infants and young children 4 weeks to less than 6 years of age and/or less than 25 kg are under discussion.
R/F/TAF 25/200/25 mg is approved for the treatment of adults and adolescents ages 12 years and older weighing at least 35 kg without NNRTI, TDF or FTC resistance, and with a viral load less than 100,000 copies/mL. 
The adult dose will also be investigated for children 6 to less than 12 years, and age appropriate formulations for ages 4 weeks to less than 12 years, but these are deferred until more is known about the individual components. There is a waiver for infants less than 4 weeks. 
Non-nucleoside reverse transcriptase inhibitors
A scored 25 mg etravirine (ETR) tablet with dosing recommendations for treatment-experienced children and adolescents aged 6 to less than 18 years and weighing at least 16 kg is currently approved.  The recommended dose is based on 5.2 mg/kg twice daily.
IMPAACT P1090 is evaluating the drug in treatment-naive and -experienced children aged 2 months to 6 years. [18, 19, 20] Phase 1/2 studies in the younger age groups are currently enrolling treatment-experienced children.
There is a waiver for infants from birth to less than two months.
Rilpivirine (RPV) is approved for treatment of adults and adolescents 12 years of age and above with viral load less than 100,000 copies/mL at 25 mg once daily.
RPV is also being developed as a co-formulation with DTG and an intramuscular long acting formulation for treatment and prevention (see below).
Once-daily 100 mg doravirine is currently under investigation in adults.  The originator company Merck has a full paediatric development plan for doravirine including the FDC of doravirine plus TDF plus 3TC (from birth to 18 years of age and the latter going down to 2 years of age). 
The studies will enrol populations similar to those in adult phase 3 studies: treatment-naive and stable experienced patients for switch studies.  The first study in adolescents is planned to open by the end of this year.
Reduced strength tablets and granules are in development.
Raltegravir (RAL) is approved for infants and children from four weeks of age. 
For the youngest age group (four weeks to less than two years, weighing 3 kg to 20 kg) it is formulated as granules for oral suspension. The formulation comes in single-use packets of banana-flavoured granules containing 100 mg of RAL, which is suspended in 5 mL of water giving a final concentration of 20 mg/mL. Giving RAL to neonates currently requires a complex dosing regimen.
For older children, there is an orange-banana flavoured, chewable paediatric formulation: 25 and 100 mg tablets. Because the formulations are not bioequivalent, chewable tablets and the oral suspension are not interchangeable and have specific guidance.
There have been discussions about the possibility of using the chewable formulation in younger age groups, as the granules for oral suspension are complicated to use.
The chewable tablets can be prepared by wetting, crushing, and stirring in water, apple juice, or breast milk until dispersed. This could mean simpler administration to younger children following WHO weight bands.  Although in vitro data suggest this will result in therapeutic plasma levels, there are no efficacy/safety data to support this use.
The development of EVG as a single formulation for children was recently stopped. EVG is being studied as part of E/C/F/TAF (see above) and E/C/F/TDF.
DTG is approved for children ages 6 years and above, weighing at least 30 kg (FDA) or 15 kg (EMA). [36, 37] Reduced strength formulations are 10mg and 25mg oral tablets.
DTG also has a very comprehensive development programme and is being studied in age groups down to 4 weeks in IMPAACT P1093. 
A 5 mg dispersible tablet formulation of DTG is being developed (as an alternative to the granule formulation that was originally used in early studies) for infants and young children. The dispersible tablet and granule formulations are bioequivalent.  DTG PK is not affected by water mineral content or 30-minute delay in dispersed tablet consumption. The dispersible tablet can be given under these conditions.
Taste masking work on the dispersible tablets is ongoing. The tablets will be strawberry cream flavoured. Only the dispersible tablets will be available commercially.
The DTG/ABC/3TC PIP requires data from IMPAACT P1093 in the 2 to less than 12 years of age group to inform DTG dosing. 
The investigation plan also requires the completion of a DTG/ABC/3TC FDC paediatric study in 2 to 12 year olds. This will be an open-label, switch design and enrol children who are fully suppressed on ART and integrase inhibitor-naive.
There is a waiver from birth to less than 2 years old.
The current plan for a paediatric DTG/RPV FDC is as a maintenance regimen in children and adolescents aged six to less than18 years and virologically suppressed. 
Data from planned adult phase 3 studies and existing adolescent data from single agents will be used for the 12 to less than 18 years age group. Providing the adult data supports the maintenance strategy, dosing studies and paediatric FDC development will then go ahead in the 6 to 12 age group.
There is a waiver from birth to less than 6 years old.
The plan for DTG/3TC FDC is for ART naive adolescents above 12 to less than 18 years with viral load less than 500,000 copies/mL and virologically suppressed children and adolescents aged 2 to less than 18 years. 
There is a waiver from birth to less than 2 years old.
In development as part of B/F/TAF (see above).
Cabotegravir and rilpivirine long-acting
Cabotegravir (CAB) is under investigation for adults as a long-acting formulation with RPV (CAB/RPV LA). An age appropriate formulation will be developed for induction and the intramuscular nanosuspension will be the same as for adults (adult/adolescent doses: 3mL loading, 2mL maintenance).
The PIP includes PK, safety, tolerability, durability, acceptability and maintenance of CAB and RPV in 2 to 18 year olds (prevention studies from 12 to less than 18 years).
A waiver was granted for children from birth to less than two years and a deferral for 2 to 18 year olds. 
IMPAACT 2017 – a phase 1/2 study will look at CAB/RPV LA in approximately 155 virologically suppressed children and adolescents aged 12 to less than 18 years. Antiviral activity will be assessed as part of safety evaluations. 
Cobicistat and formulations
COBI is a CYP3A inhibitor with no antiretroviral activity. COBI 150 mg is approved for adults as a booster of atazanavir (ATV) 300 mg or DRV 800 mg and as part of several FDCs. It is under investigation for children and adolescents aged at least six years as a part of E/C/F/TDF and E/C/F/TAF.
A 50 mg paediatric immediate-release tablet and a 20 mg paediatric dispersible tablet are in development. 
COBI is being studied in treatment-experienced children aged three months to 18 years who are suppressed and on RTV boosted atazanavir (ATV)- or darunavir (DRV)-containing regimens. The study will switch children from RTV to COBI and look at steady state PK and confirm the dose. It will also evaluate the safety, tolerability, and efficacy of ATV/COBI or DRV/COBI.
There are waivers from birth to 3 months, 3 years and 6 years for ATV/c, DRV/c and D/C/F/TAF respectively.
HIV Neutralising Monoclonal Antibody
As a slight departure from antiretrovirals, first data from VRC01 – an investigational HIV neutralising monoclonal antibody administered subcutaneously to neonates – were presented this year. 
Preliminary results from IMPAACT P1112 suggest that its half-life would support monthly injections for those at risk of HIV through breastfeeding.
This is an ongoing, prospective, open label, dose escalating study of VRC01, given to infants at increased risk of vertical transmission as a single 20 or 40 mg/kg subcutaneous dose within 72 hours of birth.
- European Medicines Agency. Opinions and decisions on paediatric investigation plans.
- US Food and Drug Administration. Pediatric product development.
- Gilead Sciences press release. US Food and Drug Administration approves Descovy (emtricitabine, tenofovir alafenamide), Gilead’s third TAF-based HIV therapy. 4 April 2016.
- Gilead Sciences press release. European Commission grants marketing authorization for Gilead’s fixed-dose combination Descovy (emtricitabine, tenofovir alafenamide) for treatment of HIV. 25 April 2016.
- US National Institutes of Health. Emtricitabine/tenofovir alafenamide (F/TAF) in HIV-1 infected children and adolescents virologically suppressed on a 2-NRTI-containing regimen.
- European Medicines Agency. Emtricitabine/tenofovir alafenamide PIP. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-001577-PIP02-14-M01/pip_001284.jsp&mid=WC0b01ac058001d129
- US National Institutes of Health. Pharmacokinetics, safety, and antiviral activity of the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate (E/C/F/TAF) single tablet regimen (STR) in HIV-1 infected antiretroviral treatment-naive adolescents and virologically suppressed children.
- US National Institutes of Health. A Phase 2/3 open-label study to evaluate the safety and efficacy of E/C/F/TAF in HIV-1 infected virologically suppressed adolescents.
- European Medicines Agency. E/C/F/TAF PIP.
- Gaur A et al. Safety and efficacy of E/C/F/TAF in HIV-1–Infected treatment-naive adolescents. CROI 2016. 22–25 February 2016. Boston, Massachusetts. Poster abstract 817.
- Gaur A et al. Pharmacokinetics, safety & efficacy of E/C/F/TAF in HIV-infected children (6–12 yrs). CROI 2017. 13–17 February 2017. Seattle, Washington. Poster abstract 424.
- Gilead press release. Gilead submits new Drug Application to US Food and Drug Administration for fixed-dose combination of bictegravir, emtricitabine and tenofovir alafenamide for HIV treatment. 12 June 2017.
- US National Institutes of Health. B/F/TAF FDC in HIV-1 infected virologically suppressed adolescents and children.
- European Medicines Agency. Bictegravir/emtricitabine/tenofovir alfenamide PIP. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-001766-PIP01-15-M01/pip_001402.jsp&mid=WC0b01ac058001d129
- Gilead press release. European Commission grants marketing authorization for Gilead’s single tablet regimen Odefsey (emtricitabine, rilpivirine, tenofovir alafenamide) for the treatment of HIV. 23 June 2016.
- European Medicines Agency. Rilpivirine/emtricitabine/tenofovir alfenamide PIP.
- US Food and Drug Administration. Intelence (etravirine): pediatric dosing recommendations and new scored 25 mg tablet for pediatric dosing. 26 March 2012.
- US National Institutes of Health. Evaluating the safety and tolerability of etravirine in HIV-1 infected infants and children
- IMPAACT P1090. Version 5.0. 10 March 2016.
- European Medicines Agency. Etravirine PIP. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-000222-PIP01-08-M08/pip_000191.jsp&mid=WC0b01ac058001d129
- IMPAACT P1111. 7 April 2014.
- US National Institutes of Health. Safety, tolerability, drug interactions, and antiviral activity of rilpivirine in antiretroviral-naive HIV-infected children less than 12 years of age.
- Molina JM et al. Doravirine is non-inferior to darunavir/r in phase 3 treatment-naive trial at week 48. CROI 2017. 13-16 February 2017. Seattle. Late breaker oral abstract 45LB.
- European Medicines Agency. Doravirine PIP.
- IMPAACT 2014: Phase I/II study of the pharmacokinetics, safety and tolerability of doravirine (MK-1439) and doravirine/lamivudine/tenofovir disoproxil fumarate
(MK-1439A) in HIV-1-infected children and adolescents.
- US Food and Drug Administration. New Isentress (raltegravir) dosage form: oral suspension. 20 December 2014.
- Teppler H et al. Crushing of raltegravir (RAL) chewable tablets for administration in infants and young children. 9th International Workshop on HIV Pediatrics 2017. 21–22 July 2017. Paris. Forthcoming.
- US National Institutes of Health. Safety and effectiveness of raltegravir in HIV-infected children and adolescents.
- US National Institutes of Health. Safety and pharmacokinetics of raltegravir in HIV-1-exposed newborn infants at high risk of acquiring HIV-1 infection.
- US National Institutes of Health. Evaluating the safety and pharmacokinetics of raltegravir in infants.
- Nachman S et.al. Pharmacokinetics and 48-Week safety and efficacy of raltegravir for oral Suspension in Human Immunodeficiency Virus type-1-infected children 4 weeks to 2 years of age. J Ped Infect Dis 2015.
- Clarke DF et.al. Raltegravir pharmacokinetics in neonates following maternal dosing. J Acquir Immun Defic Syndr. 2014;67:310-315.
- Rizk ML et.al. Population pharmacokinetic analysis of raltegravir pediatric formulations in HIV-infected children 4 weeks to 18 years of age. J Clin Pharmacol 2015; 55:748-756.
- Clarke DF et al. Raltegravir (RAL) pharmacokinetics (PK) and safety in HIV-1 exposed neonates at high-risk of infection (IMPAACT P1110). 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention.19-22 July 2015. Vancouver. Poster abstract MOPEB196.
- Clarke DF et al. Raltegravir pharmacokinetics and safety in HIV-1 exposed neonates: dose-finding study. CROI 2017.13–17 February 2017. Seattle. Poster abstract 757.
- ViiV Healthcare press release. ViiV Healthcare announces FDA approval to lower the weight limit for dolutegravir in children and adolescents living with HIV. 10 June 2016.
- ViiV Healthcare welcomes European Commission approval of dolutegravir paediatric Type II variation and extension applications. 27 February 2017.
- US National Institutes of Health. Safety of and immune response to dolutegravir (GSK1349572) in HIV-1 Infected infants, children, and adolescents.
- Viani RM et al. Safety and efficacy of dolutegravir in HIV treatment-experienced adolescents: 48-week results. CROI 2014. 3-6 March 2014, Boston. Poster abstract 906LB.
- Viani RM et al. Safety, pharmacokinetics and efficacy of dolutegravir in treatment-experienced HIV+ children. CROI 2014. 3-6 March 2014. Boston.Poster abstract 901.
- Wiznia A et al. IMPAACT 1093: dolutegravir in 6- to 12-year-old HIV-infected children: 48-Week results. CROI 2016. 22–25 February 2016.
Boston. Poster abstract 816.
- Song S et al. Relative bioavailability of a dolutegravir (DTG) dispersible tablet and the effect of low and high mineral content water on the tablet in healthy adult volunteers. 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015). 19-22 July 2015. Vancouver. Poster abstract MOPEB200.
- ViiV Healthcare. ViiV Healthcare receives FDA approval for Triumeq. 22 August 2014.
- ViiV Healthcare. ViiV Healthcare receives EU marketing authorisation for Triumeq. (dolutegravir/abacavir/lamivudine), a new once-daily single-pill regimen for the treatment of HIV. 3 September 2014.
- European Medicines Agency. Dolutegravir/abacavir/lamivudine PIP.
- European Medicines Agency. Dolutegravir/rilpivirine PIP.
- European Medicines Agency. Dolutegravir/lamivudine PIP. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-001940-PIP01-16/pip_001587.jsp&mid=WC0b01ac058001d129
- European Medicines Agency. Cabotegravir/rilpivirine LA PIP.
- IMPAACT 2017: phase I/II study of the safety and pharmacokinetics of oral and injectable cabotegravir and rilpivirine in virologically suppressed HIV-Infected adolescents.
- European Medicines Agency. Cobicistat PIP.
- European Medicines Agency. Atazanavir/cobicistat PIP. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-001465-PIP01-13/pip_001168.jsp&mid=WC0b01ac058001d129
- European Medicines Agency. Darunavir/cobicistat PIP. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-001280-PIP01-12/pip_000989.jsp&mid=WC0b01ac058001d129
- European Medicines Agency. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide PIP.
- Cunningham CK et al. Safety & pharmacokinetics of the monoclonal antibody, VRC01, in HIV-exposed newborns. CROI 2017. 13-17 February 2017. Seattle. Poster abstract 760.
- IMPAACT P1112 (DAIDS ID 11903): open-label, dose-escalating, phase I study to determine safety and pharmacokinetic parameters of subcutaneous (SC) VRC01 and VRC01LS, potent anti-HIV neutralizing monoclonal antibodies, in HIV-1-exposed infants.
- IMPAACT 2008 (DAIDS ID 20735): phase I/II multisite randomized controlled study of monoclonal antibody VCR01 combined with antiretroviral therapy to promote clearance of HIV-1 infected cells in infants.