Virologic failure among children taking lopinavir/ritonavir-containing first-line antiretroviral therapy in South Africa.
OBJECTIVE
To report the outcomes, clinical management decisions and results of resistance testing among a group of children who developed virologic failure on first-line lopinavir/ritonavir (LPV/r)-based therapy from a large cohort of antiretroviral therapy-treated children in Soweto.


METHODS
Historical cohort study.


METHODS
Children with virologic failure were identified from a group of 1692 children <3 years who had initiated first-line LPV/r-containing therapy since 2000 up to the end November 2011. Genotyping was conducted in some children, and outcomes, management decisions and resistance results were described.


RESULTS
A total of 152 children with virologic failure on first-line LPV/r-containing antiretroviral therapy were included. Resistance testing was performed in 75/152 (49%), and apart from a younger age (11.1 vs. 15.1 months, P = 0.04), the children with versus those without resistance testing were similar for baseline characteristics (weight, CD4, viral load and time to failure). Genotyping revealed that 8/75 (10.7%) had significant LPV/r-associated resistance mutations, including 2 with intermediate darunavir resistance. Among 63/75 (84%) children remaining on LPV/r-based therapy, 32/63 (51%) achieved virologic suppression, and 2 of these children with significant LPV mutations. In accordance with the local guidelines at the time, 12/152 (8%) children were switched to non-nucleoside reverse-transcriptase inhibitors-based therapy. Of these, 4/12 (33%) resuppressed, and the rest did not achieve virologic suppression including the 2 with lopinavir mutations.


CONCLUSIONS
Virologic failure of LPV/r-containing first-line regimens is associated with accumulation of LPV/r mutations in children. The implications are unclear, and surveillance at selected sites is warranted for long-term virologic outcomes and development of resistance.
From the *Department of Paediatrics, Chris Hani Baragwanath Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; †Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; ‡Division of Epidemiology and Biostatistics, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; §Empilweni Services and Research Unit (ESRU), Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; and ¶Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service, Tygerberg, South Africa.
Tammy
T
Meyers
Shobna
S
Sawry
Jessica Y
JY
Wong
Harry
H
Moultrie
Francoise
F
Pinillos
Lee
L
Fairlie
Gert
G
van Zyl
D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D002675:Child, Preschool; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006678:HIV / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007223:Infant; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D020125:Mutation, Missense; D019438:Ritonavir / Q000627:therapeutic use*; D013019:South Africa; D017211:Treatment Failure; D019562:Viral Load
D044966:Anti-Retroviral Agents; D061466:Lopinavir; D019438:Ritonavir