Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Dec 1;75(12):3433-3457.
doi: 10.1093/jac/dkaa328.

Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review

Tom G Jacobs  1 , Elin M Svensson  1   2 , Victor Musiime  3   4 , Pablo Rojo  5 , Kelly E Dooley  6 , Helen McIlleron  7 , Rob E Aarnoutse  1 , David M Burger  1 , Anna Turkova  8 , Angela Colbers  1 ; WHO Paediatric Antiretroviral Working Group
Collaborators, Affiliations

Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review

Tom G Jacobs et al. J Antimicrob Chemother. .

Abstract

Introduction: Management of concomitant use of ART and TB drugs is difficult because of the many drug-drug interactions (DDIs) between the medications. This systematic review provides an overview of the current state of knowledge about the pharmacokinetics (PK) of ART and TB treatment in children with HIV/TB co-infection, and identifies knowledge gaps.

Methods: We searched Embase and PubMed, and systematically searched abstract books of relevant conferences, following PRISMA guidelines. Studies not reporting PK parameters, investigating medicines that are not available any longer or not including children with HIV/TB co-infection were excluded. All studies were assessed for quality.

Results: In total, 47 studies met the inclusion criteria. No dose adjustments are necessary for efavirenz during concomitant first-line TB treatment use, but intersubject PK variability was high, especially in children <3 years of age. Super-boosted lopinavir/ritonavir (ratio 1:1) resulted in adequate lopinavir trough concentrations during rifampicin co-administration. Double-dosed raltegravir can be given with rifampicin in children >4 weeks old as well as twice-daily dolutegravir (instead of once daily) in children older than 6 years. Exposure to some TB drugs (ethambutol and rifampicin) was reduced in the setting of HIV infection, regardless of ART use. Only limited PK data of second-line TB drugs with ART in children who are HIV infected have been published.

Conclusions: Whereas integrase inhibitors seem favourable in older children, there are limited options for ART in young children (<3 years) receiving rifampicin-based TB therapy. The PK of TB drugs in HIV-infected children warrants further research.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Metabolic pathways and inducing/inhibitory potential of antiretroviral and TB drugs. X = metabolic pathway; X(M) = main metabolic pathway; green box = induction; red box = inhibition; yellow box = both induction and inhibition; X(U) = other hepatic metabolic pathway or unknown metabolic pathway. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.
Figure 2.
Figure 2.
PRISMA flow chart.
See this image and copyright information in PMC

References

    1. UNAIDS. Global AIDS Update 2019 https://www.unaids.org/sites/default/files/media_asset/2019-global-AIDS-....
    1. World Health Organization. Global Tuberculosis Report 2019. https://www.who.int/tb/publications/global_report/en/.
    1. Gortmaker SL, Hughes M, Cervia J et al. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. N Engl J Med 2001; 345: 1522–8. - PubMed
    1. 4.The KIDS-ART-LINC Collaboration. Low risk of death, but substantial program attrition, in pediatric HIV treatment cohorts in Sub-Saharan Africa. J Acquir Immune Defic Syndr 2008; 49: 523–31. - PubMed
    1. UNICEF. Paediatric Care and Treatment. https://data.unicef.org/topic/hivaids/paediatric-treatment-and-care/.

Publication types