Super-booster therapy for children living with HIV and tuberculosis Paediatric HIV
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 (LPV/r), 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 problem that is especially acute in southern African countries at the heart of the HIV epidemic.
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 – in 2013 to demonstrate the safety and effectiveness of ‘super-boosting,’ which involves adding extra ritonavir to the LPV/r regimen. This study took place at five hospitals in South Africa in infants and youngchildren 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 LPV/r and rifampicin.
The results were presented to the WHO guidelines review committee and have strengthened the WHO’s recommendation in 2016 to use super-boosting in TB/HIV co-infected children when on a LPV/r-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.
At a glance
Indication: Paediatric HIV/TB co-infection
Dosage: Super-boosting’ ritonavir at 1:1 ratio with lopinavir to treat HIV; rifampicin to treat TB
Project start: 2012
- 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.”
Key scientific articles
Abacavir exposure in children co-treated for tuberculosis with rifampicin and super-boosted lopinavir-ritonavir. Antimicrobial Agents and Chemotherapy, February 2020
by Rabie H, Tikiso T, Lee J, Fairlie L, Strehlau R, Bobat R, Liberty A, McIlleron H, Andrieux-Meyer I, Cotton M, Lallemant M, Denti P.
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, January 2019
by Rabie H, Denti P, Lee J, Masango M, Coovadia A, Pillay S, Liberty A, Simon F, McIlleron H, Cotton MF, Lallemant M.
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.
Lopinavir/ritonavi 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
Department of Health and Department of Science and Technology, South Africa; Stellenbosch University and Tygerberg Children’s Hospital, South Africa; Perinatal HIV Research Unit, University of Witswatersrand, South Africa; Shandukani Research Centre, Wits Reproductive Health and HIV Institute, South Africa; Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, South Africa; Enhancing Care Foundation, South Africa; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa.
French Development Agency (AFD), France; Médecins Sans Frontières/Doctors without Borders, International/Norway; Spanish Agency for International Development Cooperation (AECID), Spain; Swiss Agency for Development and Cooperation (SDC), Switzerland; UBS Optimus Foundation, Switzerland; UNITAID, Switzerland.
Photo credit: Mariella Furrer-DNDi, Scholars & Gentlemen-DNDi
Last updated: November 2018