Gabriela Patten1, Michael Schomaker1, Mary-Ann Davies1, Helena Rabie2, Gert van Zyl3, Karl Technau4, Brian Eley5, Andrew Boulle1, Russell B Van Dyke6, Kunjal Patel7, Nosisa Sipambo8, Robin Wood9, Frank Tanser10, Janet Giddy11, Mark Cotton12, James Nuttall5, Gadija Essack2, Brad Karalius7, George Seage7, Shobna Sawry13, Matthias Egger1,14, Lee Fairlie13. 1. From the Centre for Infectious Disease Epidemiology & Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. 2. Tygerberg Academic Hospital, University of Stellenbosch, Tygerberg, Cape Town, South Africa. 3. Division of Medical Virology, Stellenbosch University and National Health Laboratory Service, Tygerberg, Cape Town, South Africa. 4. Department of Paediatrics and Child Health, University of the Witwatersrand, Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa. 5. Red Cross War Memorial Children's Hospital, and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa. 6. Department of Pediatric, Tulane University, School of Medicine, New Orleans, LA. 7. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Centre for Biostatistics in AIDS Research (CBAR), Boston, MA. 8. Department of Paediatrics and Child Health, University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. 9. The Desmond Tutu HIV Centre, Institute for Infectious Disease & Molecular Medicine, University of Cape Town, Cape Town, South Africa. 10. Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Mtubatuba, South Africa. 11. McCord Hospital, Durban, South Africa. 12. Department of Paediatrics and Child Health Division of Paediatric Infectious Diseases, Stellenbosch University and Tygerberg Children's Hospital, Cape Town, South Africa. 13. Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa. 14. Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
Abstract
BACKGROUND: Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence, and the development of HIV resistance mutations. We aimed to evaluate 4 management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes. METHODS: We included children (< 16 years of age) with VF from 8 International Epidemiologic Database to Evaluate AIDS Southern Africa cohorts, initiating combination antiretroviral therapy (cART) between 2004 and 2010, who followed one of the 4 management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART. We compared the effect of management strategy on the 52-week change in CD4% and log10VL from VF, using inverse probability weighting of marginal structural linear models. RESULTS: Nine hundred eighty-two patients were followed over 54,168 weeks. Relative to remaining on a failing regimen, switching to second-line showed improved immunologic and virologic responses 52 weeks after VF with gains in CD4% of 1.5% (95% confidence interval [CI], 0.2-2.8) and declines in log10VL of -1.4 copies/mL (95% CI, -2.0, -0.8), while switching to holding regimens or discontinuing treatment had worse immunologic (-5.4% (95% CI, -12.1, 1.3) and -5.6% (95% CI, -15.4, 4.1) and virologic outcomes (0.2 (95% CI, -3.6, 4.1) and 0.8 (95% CI, -0.6, 2.1), respectively. CONCLUSIONS: The results provide useful guidance for managing children with VF. Consideration should be given to switching children failing first-line cART to second-line, given the improved virologic and immune responses when compared with other strategies.
BACKGROUND: Managing virologic failure (VF) in HIV-infectedchildren is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence, and the development of HIV resistance mutations. We aimed to evaluate 4 management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes. METHODS: We included children (< 16 years of age) with VF from 8 International Epidemiologic Database to Evaluate AIDS Southern Africa cohorts, initiating combination antiretroviral therapy (cART) between 2004 and 2010, who followed one of the 4 management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART. We compared the effect of management strategy on the 52-week change in CD4% and log10VL from VF, using inverse probability weighting of marginal structural linear models. RESULTS: Nine hundred eighty-two patients were followed over 54,168 weeks. Relative to remaining on a failing regimen, switching to second-line showed improved immunologic and virologic responses 52 weeks after VF with gains in CD4% of 1.5% (95% confidence interval [CI], 0.2-2.8) and declines in log10VL of -1.4 copies/mL (95% CI, -2.0, -0.8), while switching to holding regimens or discontinuing treatment had worse immunologic (-5.4% (95% CI, -12.1, 1.3) and -5.6% (95% CI, -15.4, 4.1) and virologic outcomes (0.2 (95% CI, -3.6, 4.1) and 0.8 (95% CI, -0.6, 2.1), respectively. CONCLUSIONS: The results provide useful guidance for managing children with VF. Consideration should be given to switching children failing first-line cART to second-line, given the improved virologic and immune responses when compared with other strategies.
Authors: Matthias Egger; Didier K Ekouevi; Carolyn Williams; Rita Elias Lyamuya; Henri Mukumbi; Paula Braitstein; Tyler Hartwell; Claire Graber; Benjamin H Chi; Andrew Boulle; François Dabis; Kara Wools-Kaloustian Journal: Int J Epidemiol Date: 2011-05-18 Impact factor: 7.196
Authors: George K Siberry; Kunjal Patel; Russell B Van Dyke; Rohan Hazra; Sandra K Burchett; Stephen A Spector; Mary E Paul; Jennifer S Read; Andrew Wiznia; George R Seage Journal: J Acquir Immune Defic Syndr Date: 2011-07-01 Impact factor: 3.731
Authors: Maya L Petersen; Mark J van der Laan; Sonia Napravnik; Joseph J Eron; Richard D Moore; Steven G Deeks Journal: AIDS Date: 2008-10-18 Impact factor: 4.177
Authors: Yuan Ren; James J C Nuttall; Claire Egbers; Brian S Eley; Tammy M Meyers; Peter J Smith; Gary Maartens; Helen M McIlleron Journal: J Acquir Immune Defic Syndr Date: 2008-04-15 Impact factor: 3.731
Authors: Lee Fairlie; Brad Karalius; Kunjal Patel; Russell B van Dyke; Rohan Hazra; Miguel A Hernán; George K Siberry; George R Seage; Allison Agwu; Andrew Wiznia Journal: AIDS Date: 2015-10-23 Impact factor: 4.177
Authors: Sophie Desmonde; Simone C Frank; Ashraf Coovadia; Désiré L Dahourou; Taige Hou; Elaine J Abrams; Madeleine Amorissani-Folquet; Rochelle P Walensky; Renate Strehlau; Martina Penazzato; Kenneth A Freedberg; Louise Kuhn; Valeriane Leroy; Andrea L Ciaranello Journal: Open Forum Infect Dis Date: 2019-06-11 Impact factor: 3.835
Authors: Dwight E Yin; Christina Ludema; Stephen R Cole; Carol E Golin; William C Miller; Meredith G Warshaw; Ross E McKinney Journal: PLoS One Date: 2020-11-23 Impact factor: 3.240