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What Should We Do When HIV-positive Children Fail First-line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies

Patten, Gabriela, MSc*; Schomaker, Michael, Dr. rer. nat.*; Davies, Mary-Ann, PhD*; Rabie, Helena, MBChB, FCP (Paed) (SA); van Zyl, Gert, PhD; Technau, Karl, MSc (Med)§; Eley, Brian, MBChB; Boulle, Andrew, PhD*; Van Dyke, Russell B., MD; Patel, Kunjal, DSc**; Sipambo, Nosisa, MBBCH††; Wood, Robin, DSc (Med)‡‡; Tanser, Frank, PhD§§; Giddy, Janet, MFamMed¶¶; Cotton, Mark, FCPaed, (SA)‖‖; Nuttall, James, MSc (Med); Essack, Gadija, MBChB; Karalius, Brad, MPH**; Seage, George, lll DSc**; Sawry, Shobna, MSc***; Egger, Matthias, MD*,†††; Fairlie, Lee, MBChB*** for IeDEA Southern Africa

The Pediatric Infectious Disease Journal: April 2019 - Volume 38 - Issue 4 - p 400–405
doi: 10.1097/INF.0000000000002156
HIV Reports
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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.

From the *Centre for Infectious Disease Epidemiology & Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa

Tygerberg Academic Hospital, University of Stellenbosch, Tygerberg, Cape Town, South Africa

Division of Medical Virology, Stellenbosch University and National Health Laboratory Service, Tygerberg, Cape Town, South Africa

§Department of Paediatrics and Child Health, University of the Witwatersrand, Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa

Red Cross War Memorial Children’s Hospital, and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa

Department of Pediatric, Tulane University, School of Medicine, New Orleans, LA

**Department of Epidemiology, Harvard T.H. Chan School of Public Health, Centre for Biostatistics in AIDS Research (CBAR), Boston, MA

††Department of Paediatrics and Child Health, University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa

‡‡The Desmond Tutu HIV Centre, Institute for Infectious Disease & Molecular Medicine, University of Cape Town, Cape Town, South Africa

§§Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Mtubatuba, South Africa

¶¶McCord Hospital, Durban, South Africa

‖‖Department of Paediatrics and Child Health Division of Paediatric Infectious Diseases, Stellenbosch University and Tygerberg Children’s Hospital, Cape Town, South Africa

***Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa

†††Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.

Accepted for publication June 14, 2018.

Supported by funding from the United States National Institutes of Health Grant 5U01AI069924. M.E. is supported by the Swiss National Science Foundation, grant 32FP30-174281. The authors declare that there are no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).

Address for correspondence: Gabriela Patten, MSc, Centre for Infectious Disease Epidemiology & Research, School of Public Health & Family Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, South Africa. E-mail: gem.patten@uct.ac.za.

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