Limited data are available from the developing world on antiretroviral drug resistance in
HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in
the context of a high tuberculosis burden. We describe the proportion of children with drug
resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as
Data from children initiated on protease inhibitor-based antiretroviral therapy with subsequent
virological failure referred for genotypic drug resistance testing between 2008 and
2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined
and associations with these mutations identified through logistic regression analysis.
The study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly
advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median
weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;-
2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis
co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations
were found in 49% of children and associated with low weight-for-age and height-for-age
(p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure
(p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative
months on protease inhibitor regimens and use of ritonavir as single protease inhibitor
remained significant (p = 0.008; p = 0.033).
Major protease inhibitor resistance mutations were common in this study of HIV-1-infected
children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing
strategy proving to be important associated factors. There is an urgent need for safe, effective,
and practicable HIV/tuberculosis co-treatment in young children and the optimal timing
of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment
strategies should be urgently addressed.
All files are available
from the GenBank database under accession
Ms LAW Hahne for the development of the electronic database for the Kalafong clinic. Mr T
Moto for the assistance with data collection. Drs G Malherbe and P Mahasha for assisting with
the development of the genotyping assay and the staff at the HIV clinics for their dedicated service
to patients and their assistance with data collection.
Conceived and designed the experiments: TR UF. Performed the experiments: GVD. Analyzed
the data: GM. Contributed reagents/materials/analysis tools: TR GM. Wrote the paper: TR UF
GM GVD WT NDP TA.