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HIV‐1 drug resistance mutations in children after failure of first‐line nonnucleoside reverse transcriptase inhibitor‐based antiretroviral therapy
Author(s) -
Puthanakit T,
Jourdain G,
Hongsiriwon S,
Suntarattiwong P,
Chokephaibulkit K,
Sirisanthana V,
Kosalaraksa P,
Petdachai W,
Hansudewechakul R,
Siangphoe U,
Suwanlerk T,
Ananworanich J
Publication year - 2010
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2010.00828.x
Subject(s) - medicine , reverse transcriptase inhibitor , resistance mutation , interquartile range , etravirine , reverse transcriptase , hiv drug resistance , confidence interval , drug resistance , nucleoside reverse transcriptase inhibitor , odds ratio , virology , viral load , genotyping , genotype , antiretroviral therapy , human immunodeficiency virus (hiv) , biology , polymerase chain reaction , genetics , gene
Objectives 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. Methods 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. Results 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. Conclusions 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.