HIV-1 drug resistance mutations in children after failure of first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy
Puthanakit, T.; Jourdain, G.; Hongsiriwon, S.; Suntarattiwong, P.; Chokephaibulkit, K.; Sirisanthana, V.; Kosalaraksa, P.; Petdachai, W.; Hansudewechakul, R.; Siangphoe, U.; Suwanlerk, T.; Ananworanich, J.; Bunupuradah, T.; Phasomsap, C.; Kaew-on, P.; Kanjanavanit, S.; Hinjiranandana, T.; Layangool, P.; Kamonpakorn, N.; Buranabanjasatean, S.; Ngampiyaskul, C.; Chotpitayasunondh, T.; Chanpradub, S.; Leawsrisuk, P.; Chearskul, S.; Vanprapar, N.; Phongsamart, W.; Lapphra, K.; Chearskul, P.; Wittawa
HIV Medicine 11(9): 565-572
2010
ISSN/ISBN: 1468-1293 PMID: 20345882 DOI: 10.1111/j.1468-1293.2010.00828.xDocument Number: 212532
The aim of the study was to assess the prevalence, predictors and patterns of genotypic resistance mutations in children after failure of World Health Organization-recommended initial nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment regimens. We carried out a multicentre retrospective study of genotyping tests performed for all HIV-infected children at eight paediatric centres in Thailand who experienced failure of NNRTI therapy at a time when virological monitoring was not routinely available. One hundred and twenty children were included in the study. Their median age (interquartile range) was 9.1 (6.8-11.0) years, the median duration of their NNRTI regimens was 23.7 (15.7-32.6) months, their median CD4 percentage was 12% (4-20%), and their median plasma HIV RNA at the time of genotype testing was 4.8 (4.3-5.2) log(10) HIV-1 RNA copies/mL. The nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations found were as follows: 85% of the children had M184V/I, 23% had at least four thymidine analogue mutations, 12% had the Q151M complex, 5% had K65R, and 1% had the 69 insertion. Ninety-eight per cent of the children had at least one NNRTI resistance mutation, and 48% had etravirine mutation-weighted scores ≥4. CD4 percentage <15% prior to switching regimens [odds ratio (OR) 5.49; 95% confidence interval (CI) 2.02-14.93] and plasma HIV RNA>5 log(10) copies/mL (OR 2.46; 95% CI 1.04-5.82) were independent predictors of at least four thymidine analogue mutations, the Q151M complex or the 69 insertion. In settings without routine viral load monitoring, second-line antiretroviral therapy regimens should be designed assuming that clinical or immunological failure is associated with high rates of multi-NRTI resistance and NNRTI resistance, including resistance to etravirine.