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Virologic failure and second-line antiretroviral therapy (ART) in children in South Africa: the international epidemiologic databases to evaluate AIDS (IeDEA) Southern Africa collaboration
Presented by Mary-Ann Davies (South Africa).
M.-A. Davies1, R. Wood2,3, G. Van Cutsem4,5, J. Giddy6, B. Eley7,8, H. Rabie9, H. Moultrie10,11, K. Technau10,12, A. Boulle1, International Epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA)
1University of Cape Town, Infectious Diseases Epidemiology Unit, School of Public Health and Family Medicine, Cape Town, South Africa, 2University of Cape Town, Desmond Tutu HIV Centre, Institute for Infectious Diseases and Molecular Medicine, Cape Town, South Africa, 3Gugulethu Community Health Centre, Cape Town, South Africa, 4Medecins Sans Frontieres, Cape Town, South Africa, 5Khayelitsha Community Health Centre, Cape Town, South Africa, 6McCord Hospital, Durban, South Africa, 7University of Cape Town, School of Child and Adolescent Health, Cape Town, South Africa, 8Red Cross Children's Hospital, Cape Town, South Africa, 9University of Stellenbosch, Tygerberg Academic Hospital, Stellenbosch, South Africa, 10University of Witwatersrand, Paediatric HIV Clinics, Johannesburg, South Africa, 11Chris Hani Baragwanath Hospital, Harriet Shezi Clinic, Johannesburg, South Africa, 12Coronation Women and Children Hospital, Johannesburg, South Africa
Background: As more children access ART, increasing numbers will experience treatment failure and require second-line. There is no single definition of virologic failure in children, and studies of failure and outcomes on second-line from resource-limited settings are lacking. We used data from IeDEA Southern Africa paediatric ART cohorts to examine:
- Probability and determinants of virologic failure.
- Outcomes of children on second-line.
Methods: ART-naïve children (< 16 years) initiating triple therapy at IeDEA Southern Africa sites with routine 6-monthly virologic monitoring were included. Virologic failure was defined as two consecutive viral loads >10000 copies/ml more than 5 months after ART start. Kaplan-Meier estimates of probability of failure as well as outcomes after switch were determined. Cox-proportional hazards models stratified by site were used to examine associations between baseline characteristics and failure.
Results: Median (IQR) follow-up of 5484 children was 16 (6-29) months. Virologic failure occurred in 310 children and 146 were switched with cumulative probabilities of 11.4% (95%CI: 10.1-12.8) and 6.0% (95% CI: 5.0-7.2) at 3 years respectively. The median (IQR) interval between failure and switch was 4.8 (1.5-9.4) months.
| Variable | Number of children (%) | Adjusted HR (95% CI) | | Age <12 months | 1158/5484 (21) | 1.14 (0.76 - 1.71) | | Viral load >1 million copies/ml | 790/3745 (21) | 1.88 (1.33 - 2.68) | | Severe immune suppression
(WHO definition) | 3758/4576 (82) | 2.01 (1.20 - 3.36) | | WHO stage 3 or 4 | 2887/3832 (75) | 1.40 (0.95 - 2.06) | | Ritonavir used alone as third drug
(vs Lopinavir/ritonavir or NNRTI) | 382/5484 (7) | 2.69 (1.72 - 4.20) |
Survival and retention in care 1 year after switch were 97.1% (95%CI: 91.9-99.1) and 88.7% (95% CI: 81.7-93.5) respectively with 55% being virologically suppressed.
Conclusions: Approximately 50% of children with virologic failure were not switched, with a notable delay between failure and switching. Ritonavir strongly independently predicts virologic failure.
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