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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Inadequate Lopinavir Concentrations With Modified 8-Hourly Lopinavir/Ritonavir 4:1 Dosing During Rifampicin-based Tuberculosis Treatment in Children Living With HIV
Pediatric Infectious Disease Journal, Volume 42, No. 10, Year 2023
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Description
Background: Lopinavir/ritonavir plasma concentrations are profoundly reduced when co-administered with rifampicin. Super-boosting of lopinavir/ritonavir is limited by nonavailability of single-entity ritonavir, while double-dosing of co-formulated lopinavir/ritonavir given twice-daily produces suboptimal lopinavir concentrations in young children. We evaluated whether increased daily dosing with modified 8-hourly lopinavir/ritonavir 4:1 would maintain therapeutic plasma concentrations of lopinavir in children living with HIV receiving rifampicin-based antituberculosis treatment. Methods: Children with HIV/tuberculosis coinfection weighing 3.0 to 19.9 kg, on rifampicin-based antituberculosis treatment were commenced or switched to 8-hourly liquid lopinavir/ritonavir 4:1 with increased daily dosing using weight-band dosing approach. A standard twice-daily dosing of lopinavir/ritonavir was resumed 2 weeks after completing antituberculosis treatment. Plasma sampling was conducted during and 4 weeks after completing antituberculosis treatment. Results: Of 20 children enrolled; 15, 1-7 years old, had pharmacokinetics sampling available for analysis. Lopinavir concentrations (median [range]) on 8-hourly lopinavir/ritonavir co-administered with rifampicin (n = 15; area under the curve0-24 55.32 mg/h/L [0.30-398.7 mg/h/L]; Cmax 3.04 mg/L [0.03-18.6 mg/L]; C8hr 0.90 mg/L [0.01-13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve24 121.63 mg/h/L [2.56-487.3 mg/h/L]; Cmax 9.45 mg/L [0.39-26.4 mg/L]; C12hr 3.03 mg/L [0.01-17.7 mg/L]). During and after rifampicin cotreatment, only 7 of 15 (44.7%) and 8 of 12 (66.7%) children, respectively, achieved targeted pre-dose lopinavir concentrations ≥1mg/L. Conclusions: Modified 8-hourly dosing of lopinavir/ritonavir failed to achieve adequate lopinavir concentrations with concurrent antituberculosis treatment. The subtherapeutic lopinavir exposures on standard dosing after antituberculosis treatment are of concern and requires further evaluation. © 2023 Lippincott Williams and Wilkins. All rights reserved.
Authors & Co-Authors
Chabala, Chishala
Zambia, Lusaka
University of Zambia
South Africa, Cape Town
University of Cape Town
Zambia, Lusaka
University Teaching Hospital Lusaka
India, Chennai
Institute of Child Health and Hospital for Children India
Turkova, Anna
United Kingdom, London
Medical Research Council
Kapasa, Monica Lulu
Zambia, Lusaka
University Teaching Hospital Lusaka
India, Chennai
Institute of Child Health and Hospital for Children India
LeBeau, Kristen
United Kingdom, London
Medical Research Council
India, Chennai
Institute of Child Health and Hospital for Children India
Tembo, Chimuka H.
Zambia, Lusaka
University Teaching Hospital Lusaka
Zimba, Kevin M.
Zambia, Lusaka
University Teaching Hospital Lusaka
India, Chennai
Institute of Child Health and Hospital for Children India
Weisner, Lubbe
South Africa, Cape Town
University of Cape Town
Zyambo, Khozya Davie
Zambia, Lusaka
University Teaching Hospital Lusaka
India, Chennai
Institute of Child Health and Hospital for Children India
Choo, Louise L.
United Kingdom, London
Medical Research Council
India, Chennai
Institute of Child Health and Hospital for Children India
Chungu, Chalilwe
Zambia, Lusaka
University Teaching Hospital Lusaka
India, Chennai
Institute of Child Health and Hospital for Children India
Lungu, Joyce Chipili
Zambia, Lusaka
University Teaching Hospital Lusaka
India, Chennai
Institute of Child Health and Hospital for Children India
Mulenga, Veronica
Zambia, Lusaka
University Teaching Hospital Lusaka
India, Chennai
Institute of Child Health and Hospital for Children India
Crook, Angela M.
United Kingdom, London
Medical Research Council
Gibb, Diana M.
United Kingdom, London
Medical Research Council
McIlleron, Helen Margaret
South Africa, Cape Town
University of Cape Town
South Africa, Cape Town
Wellcome Centre for Infectious Diseases Research in Africa
Gibb, Diana M.
India, Chennai
Institute of Child Health and Hospital for Children India
Wills, Genevieve Helen
India, Chennai
Institute of Child Health and Hospital for Children India
Thomason, Margaret J.
India, Chennai
Institute of Child Health and Hospital for Children India
Owen-Powell, Ellen
India, Chennai
Institute of Child Health and Hospital for Children India
Baptiste, David
India, Chennai
Institute of Child Health and Hospital for Children India
McGowan, Charlotte
India, Chennai
Institute of Child Health and Hospital for Children India
Spyer, Moira J.
India, Chennai
Institute of Child Health and Hospital for Children India
Shingalili, Ellen
India, Chennai
Institute of Child Health and Hospital for Children India
Zulu, Semy
India, Chennai
Institute of Child Health and Hospital for Children India
Chipoya, Terence
India, Chennai
Institute of Child Health and Hospital for Children India
Kalumbi, Mox Malama
India, Chennai
Institute of Child Health and Hospital for Children India
Chola, Daniel
India, Chennai
Institute of Child Health and Hospital for Children India
Malama, Steven
India, Chennai
Institute of Child Health and Hospital for Children India
Wobudeya, Eric
India, Chennai
Institute of Child Health and Hospital for Children India
Musoke, Philippa Martha
India, Chennai
Institute of Child Health and Hospital for Children India
Nansamba, Winnie
India, Chennai
Institute of Child Health and Hospital for Children India
Ssenyonga, Mark
India, Chennai
Institute of Child Health and Hospital for Children India
Ssengooba, Willy
India, Chennai
Institute of Child Health and Hospital for Children India
Businge, Gerald
India, Chennai
Institute of Child Health and Hospital for Children India
Hesseling, Anneke Catharina
India, Chennai
Institute of Child Health and Hospital for Children India
Palmer, Megan
India, Chennai
Institute of Child Health and Hospital for Children India
Van Der Zalm, Marieke M.
India, Chennai
Institute of Child Health and Hospital for Children India
Workman, Jessica J.
India, Chennai
Institute of Child Health and Hospital for Children India
Demers, Anne Marie
India, Chennai
Institute of Child Health and Hospital for Children India
Gie, Robert Peter
India, Chennai
Institute of Child Health and Hospital for Children India
Walters, Elisabetta Ghimenton
India, Chennai
Institute of Child Health and Hospital for Children India
Hoddinott, Graeme
India, Chennai
Institute of Child Health and Hospital for Children India
Deventer, Anneen Van
India, Chennai
Institute of Child Health and Hospital for Children India
Goussard, Pierre
India, Chennai
Institute of Child Health and Hospital for Children India
Mave, Vidya
India, Chennai
Institute of Child Health and Hospital for Children India
Kinikar, Aarti Avinash
India, Chennai
Institute of Child Health and Hospital for Children India
Raichur, Priyanka A.
India, Chennai
Institute of Child Health and Hospital for Children India
Hissar, Syed S.
India, Chennai
Institute of Child Health and Hospital for Children India
Joseph, Bency
India, Chennai
Institute of Child Health and Hospital for Children India
Bhavani, Perumal Kannabiran
India, Chennai
Institute of Child Health and Hospital for Children India
Balaji, Sarath
Unknown Affiliation
Mulambo, Sylvia
United Kingdom, York
University of York
Nakalanzi, Sarah
United Kingdom, York
University of York
Aarnoutse, Rob Edward
Unknown Affiliation
Revill, Paul A.
Unknown Affiliation
Love-Koh, James
Unknown Affiliation
Walker, Simon M.
Unknown Affiliation
Mugyenyi, Peter N.
Unknown Affiliation
Darbyshire, Janet H.
Unknown Affiliation
Clayden, Polly
Unknown Affiliation
Donald, Peter Roderick
Unknown Affiliation
Singh, Varinder P.
Unknown Affiliation
Swaminathan, Soumya
Unknown Affiliation
Peto, Timothy E.A.
Unknown Affiliation
Mwinga, Alwyn G.
Unknown Affiliation
Fielding, Katherine Linda
Unknown Affiliation
Graham, Stephen Michael
Unknown Affiliation
Welch, Steven B.
Unknown Affiliation
Seddon, James Alexander
Unknown Affiliation
Whittaker, Elizabeth A.
Unknown Affiliation
Anderson, Suzanne T.B.
Unknown Affiliation
Grandjean, Louis
Unknown Affiliation
Statistics
Authors: 72
Affiliations: 7
Identifiers
Doi:
10.1097/INF.0000000000004047
ISSN:
08913668
Research Areas
Infectious Diseases
Maternal And Child Health