Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration.
BACKGROUND
With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa.


METHODS
Pooled analysis of routine individual data from children who initiated ART in 7 South African treatment programs with 6-monthly viral load and CD4 monitoring produced Kaplan-Meier estimates of probability of virologic failure (2 consecutive unsuppressed viral loads with the second being >1000 copies/mL, after ≥24 weeks of therapy) and switch to second-line. Cox-proportional hazards models stratified by program were used to determine predictors of these outcomes.


RESULTS
The 3-year probability of virologic failure among 5485 children was 19.3% (95% confidence interval: 17.6 to 21.1). Use of nevirapine or ritonavir alone in the initial regimen (compared with efavirenz) and exposure to prevention of mother to child transmission regimens were independently associated with failure [adjusted hazard ratios (95% confidence interval): 1.77 (1.11 to 2.83), 2.39 (1.57 to 3.64) and 1.40 (1.02 to 1.92), respectively]. Among 252 children with ≥1 year follow-up after failure, 38% were switched to second-line. Median (interquartile range) months between failure and switch was 5.7 (2.9-11.0).


CONCLUSIONS
Triple ART based on nevirapine or ritonavir as a single protease inhibitor seems to be associated with a higher risk of virologic failure. A low proportion of virologically failing children were switched.
School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. maryann.davies@uct.ac.za
Mary-Ann
MA
Davies
Harry
H
Moultrie
Brian
B
Eley
Helena
H
Rabie
Gilles
G
Van Cutsem
Janet
J
Giddy
Robin
R
Wood
Karl
K
Technau
Olivia
O
Keiser
Matthias
M
Egger
Andrew
A
Boulle
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use; D011247:Pregnancy; D019438:Ritonavir / Q000627:therapeutic use; D016879:Salvage Therapy / Q000379:methods*; D013019:South Africa; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D019829:Nevirapine; D019438:Ritonavir