Viral load versus CD4+ monitoring and 5-year outcomes of antiretroviral therapy in HIV-positive children in Southern Africa: A cohort-based modelling study
Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, Bern, Switzerland; Rahima Moosa Hospital, University of the Witwatersrand, Johannesburg, South Africa; School of Public Health and Family Medicine, University of Cape Town, South Africa; Khayelitsha ART Programme, Médecins Sans Frontières, India; Red Cross Children's Hospital, University of Cape Town, Cape Town, South Africa; Tygerberg Academic Hospital, University of Stellenbosch, Stellenbosch, South Africa; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa; McCord Hospital, Durban, South Africa; Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa
Objectives: Many paediatric antiretroviral therapy (ART) programmes in Southern Africa rely on CD4+ to monitor ART. We assessed the benefit of replacing CD4+ by viral load monitoring.Design: A mathematical modelling study.Methods: A simulation model of HIV progression over 5 years in children on ART, parameterized by data from seven South African cohorts. We simulated treatment programmes with 6-monthly CD4+ or 6- or 12-monthly viral load monitoring. We compared mortality, second-line ART use, immunological failure and time spent on failing ART. In further analyses, we varied the rate of virological failure, and assumed that the rate is higher with CD4+ than with viral load monitoring.Results: About 7% of children were predicted to die within 5 years, independent of the monitoring strategy. Compared with CD4+ monitoring, 12-monthly viral load monitoring reduced the 5-year risk of immunological failure from 1.6 to 1.0% and the mean time spent on failing ART from 6.6 to 3.6 months; 1% of children with CD4+ compared with 12% with viral load monitoring switched to second-line ART. Differences became larger when assuming higher rates of virological failure. When assuming higher virological failure rates with CD4+ than with viral load monitoring, up to 4.2% of children with CD4+ compared with 1.5% with viral load monitoring experienced immunological failure; the mean time spent on failing ART was 27.3 months with CD4+ monitoring and 6.0 months with viral load monitoring.Conclusion: Viral load monitoring did not affect 5-year mortality, but reduced time on failing ART, improved immunological response and increased switching to second-line ART. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
antivirus agent; nonnucleoside reverse transcriptase inhibitor; proteinase inhibitor; antiretrovirus agent; antiviral therapy; Article; CD4 lymphocyte count; child; childhood disease; cohort analysis; disease course; follow up; human; Human immunodeficiency virus infection; major clinical study; mortality; outcome assessment; patient compliance; simulation; therapy; treatment failure; treatment outcome; virus load; adolescent; Africa; CD4 lymphocyte count; CD4+ T lymphocyte; comparative study; drug monitoring; evaluation study; female; HIV Infections; immunology; infant; male; preschool child; procedures; survival; theoretical model; virology; Adolescent; Africa, Southern; Anti-Retroviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Child; Child, Preschool; Cohort Studies; Drug Monitoring; Female; HIV Infections; Humans; Infant; Male; Models, Theoretical; Survival Analysis; Treatment Outcome; Viral Load
32333B-150934, SNSF, National Institute of Allergy and Infectious Diseases; 5U01-AI069924-05, NIAID, National Institute of Allergy and Infectious Diseases