Mary-Ann Davies1, Nathan Ford, Helena Rabie, Geoffrey Fatti, Kathryn Stinson, Janet Giddy, Frank Tanser, Karl-Günter Technau, Shobna Sawry, Brian Eley, Robin Wood, Lynne M Mofenson, Olivia Keiser, Andrew Boulle. 1. From the *Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; †HIV/AIDS Department, World Health Organization, Geneva, Switzerland; ‡Tygerberg Academic Hospital, University of Stellenbosch, Stellenbosch, South Africa; §Kheth'Impilo, Cape Town, South Africa; ¶Médecins Sans Frontières, Khayelitsha, South Africa; ‖McCord Hospital, Durban, South Africa; **Hlabisa HIV Program, South Africa; ††Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa; ‡‡Wits Reproductive Health and HIV Institute, University of Witwatersrand, Johannesburg, South Africa; §§Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; ¶¶Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa; ‖‖Gugulethu HIV Program, Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa; ***Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, Maryland; and †††Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Abstract
BACKGROUND: Ongoing CD4 monitoring in patients on antiretroviral therapy (ART) with viral suppression has been questioned. We evaluated the probability of CD4 decline in children with viral suppression and CD4 recovery after 1 year on ART. METHODS: We included children from 8 South African cohorts with routine HIV-RNA monitoring if (1) they were "responders" [HIV-RNA < 400 copies/mL and no severe immunosuppression after ≥1 year on ART (time 0)] and (2) ≥1 HIV-RNA and CD4 measurement within 15 months of time 0. We determined the probability of CD4 decline to World Health Organization-defined severe immunosuppression for 3 years after time 0 if viral suppression was maintained. Follow-up was censored at the earliest of the following dates: the day before first HIV-RNA measurement >400 copies/mL; day before a >15-month gap in testing and date of death, loss to follow-up, transfer out or database closure. RESULTS: Among 5984 children [median age at time 0: 5.8 years (interquartile range: 3.1-9.0)], 270 children experienced a single CD4 decline to severe immunosuppression within 3 years of time 0 with probability of 6.6% (95% CI: 5.8-7.4). A subsequent CD4 measurement within 15 months of the first low measurement was available for 63% of children with CD4 decline and 86% showed CD4 recovery. The probability of CD4 decline was lowest (2.8%) in children aged 2 years or older with no or mild immunosuppression and on ART for <18 months at time 0. This group comprised 40% of children. CONCLUSIONS: This finding suggests that it may be safe to stop routine CD4 monitoring in children older than 2 years and rely on virologic monitoring alone.
BACKGROUND: Ongoing CD4 monitoring in patients on antiretroviral therapy (ART) with viral suppression has been questioned. We evaluated the probability of CD4 decline in children with viral suppression and CD4 recovery after 1 year on ART. METHODS: We included children from 8 South African cohorts with routine HIV-RNA monitoring if (1) they were "responders" [HIV-RNA < 400 copies/mL and no severe immunosuppression after ≥1 year on ART (time 0)] and (2) ≥1 HIV-RNA and CD4 measurement within 15 months of time 0. We determined the probability of CD4 decline to World Health Organization-defined severe immunosuppression for 3 years after time 0 if viral suppression was maintained. Follow-up was censored at the earliest of the following dates: the day before first HIV-RNA measurement >400 copies/mL; day before a >15-month gap in testing and date of death, loss to follow-up, transfer out or database closure. RESULTS: Among 5984 children [median age at time 0: 5.8 years (interquartile range: 3.1-9.0)], 270 children experienced a single CD4 decline to severe immunosuppression within 3 years of time 0 with probability of 6.6% (95% CI: 5.8-7.4). A subsequent CD4 measurement within 15 months of the first low measurement was available for 63% of children with CD4 decline and 86% showed CD4 recovery. The probability of CD4 decline was lowest (2.8%) in children aged 2 years or older with no or mild immunosuppression and on ART for <18 months at time 0. This group comprised 40% of children. CONCLUSIONS: This finding suggests that it may be safe to stop routine CD4 monitoring in children older than 2 years and rely on virologic monitoring alone.
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