Support implementation of and access to a stand-alone ritonavir booster formulation for HIV-TB co-infected children
current phase of drug development
updated 1 Jun 2021
Research proves that ‘super-boosting’ the antiretroviral ritonavir counteracts negative interactions with the common TB drug rifampicin
New hope for children co-infected with HIV and TB
The drug rifampicin is the backbone of treatment for drug-sensitive tuberculosis (TB). However, rifampicin reduces the bioavailability – and hence the effectiveness of – protease inhibitors such as lopinavir/ritonavir, which are antiretrovirals (ARVs) commonly used to treat HIV. This negative drug-drug interaction is a major challenge in treating kids that have both TB and HIV, a common occurrence that is especially acute in southern African countries at the heart of the HIV epidemic.
In 2013, as part of its development of child-adapted ARV formulations, DNDi began a pharmacokinetic study – which shows the relationship between dosing and the body’s exposure to drugs – to demonstrate the safety and effectiveness of ‘super-boosting,’ which involves adding extra ritonavir to the lopinavir/ritonavir regimen.
This study took place at five hospitals in South Africa and included 96 infants and young children co-infected with HIV and TB. Children were given a 1:1 ratio of lopinavir and ritonavir, as opposed to the previously used 4:1 ratio. In May 2015, DNDi conducted an interim analysis that demonstrated excellent safety and efficacy of the super-boosting approach. The addition of ritonavir to reach a 1:1 ratio to lopinavir perfectly counteracts the negative interactions between lopinavir/ritonavir and rifampicin.
The results were presented to the World Health Organization (WHO) Guidelines Review Committee and strengthened WHO’s recommendation in 2016 to use super-boosting in TB/HIV co-infected children who are receiving lopinavir/ritonavir-based therapy. This study was completed and final results were presented in 2017 showing that super-boosting is safe and effective for TB/HIV co-infected children.
Treatment regimens
- Indication: Paediatric HIV/TB co-infection
- Dosage: Super-boosting’ ritonavir at 1:1 ratio with lopinavir to treat HIV; rifampicin to treat TB
Impact
- Supported by interim results from DNDi’s study, super-boosting ritonavir was recommended by WHO in its antiretroviral guidelines in 2016
‘All of the infants who participated in the DNDi [super-boosting] study, when they finished the TB treatment at six months they were virally suppressed. We didn’t have any problems, meaning the ARVs did work, and the infants tested negative for TB.’
Rejoice Mosia, Nurse, King Edward VIII Hospital, South Africa
Project updates
2019
The drug rifampicin is the backbone of the regimen to treat tuberculosis (TB) in children. However, rifampicin reduces the bioavailability of protease inhibitors such as lopinavir/ritonavir (LPV/r), a major challenge in treating children infected with both HIV and TB. The results of an earlier DNDi study demonstrating the safety and effectiveness of ‘super-boosting’ (which involves adding extra ritonavir to the LPV/r regimen to counter this drug-drug interaction) strengthened WHO’s recommendation to use super-boosting in HIV/TB co-infected children when they are on an LPV/r-based therapy.
DNDi is now preparing to conduct a similar study to evaluate the 4-in-1 for treatment of young children co-infected with HIV and TB.
2018
Final results were presented in 2017 and published in 2018, showing that super-boosting is safe and effective.
2017
The results were presented to the WHO guidelines review committee and have strengthened the WHO recommendation to use super-boosting in TB/HIV co-infected children when they are on a LPV/r-based therapy. This study has been completed and final results were presented in 2017, showing that super-boosting is safe and effective.
2016
Final results show that LPV drug levels during HIV/TB co-treatment using the superboosting approach is as good as when children return to standard LPV/r-based antiretroviral therapy. Superboosting was safe and well tolerated. Results were shared with WHO to support a change in guidelines for the management of HIV/TB co-infections in children, which was done in 2016.
In 2017, a follow-on study currently awaiting ethical approval will examine the safety and efficacy of super-boosting with ritonavir powder and other solid antiretovirals including LPV/r pellets and dual NRTI dispersible tablets.
2015
The study on the pharmacokinetics and safety of superboosting LPV/r with ritonavir for treatment of children in the weight range of 3-15 kg co-infected with HIV and tuberculosis (TB) in South Africa has recruited 96 patients. An interim analysis of data from 80 study participants carried out in May 2015 showed non inferiority of superboosting LPV/r (1:1) over standard regimen LPV/r (4:1). 80% of the children achieved good viral suppression after 6 months of superboosted ART and TB therapy. There were no reported safety issues related to superboosting. The interim results were presented at the 7th International Workshop on Paediatric HIV in July 2015 and report submitted to the WHO Guidelines Technical Review Team.
News & resources
- 18 February 2020 – Abacavir exposure in children co-treated for tuberculosis with rifampicin and super-boosted lopinavir-ritonavir, Antimicrobial Agents and Chemotherapy
- 1 November 2019 – Ending the Neglect of Paediatric HIV
- 6 January 2019 – Lopinavir–ritonavir super-boosting in young HIV-infected children on rifampicin-based tuberculosis therapy compared with lopinavir–ritonavir without rifampicin: a pharmacokinetic modelling and clinical study, The Lancet HIV
- 15 February 2017 – Caring for Kids with HIV and TB
- 14 February 2017 – Study confirms key therapeutic advance for children living with HIV and tuberculosis
Additional information
Tuberculosis: opportunities and challenges for the 90-90-90 targets in HIV-infected children. Journal of the International AIDS Society, December 2015
by Rabie H, Frigati L, Hesseling AC, Garcia-Prats AJ.
Consolidated guidelines on the use of ARVs for treating and preventing HIV infection: recommendations for a public health approach. World Health Organization, 2016
Presentation
Lopinavir/ritonavir 1:1 superboosting overcomes rifampicin interactions in children
by Rabie H, Denti P, Lee J, Coovadia A, Pillay S, Liberty A, Masango M, Mcilleron H, Cotton MF, Lallemant M
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