High Rate Of Antiretroviral Drug Resistance Mutations in HIV Type 1-Infected Senegalese Children in Virological Failure on First-Line Treatment According to the World Health Organization Guidelines

Abstract

The rates of virological failure (VF) and HIV-1 drug resistance were evaluated in a cross-sectional study in HIV-1-infected children living in Dakar, and taking antiretroviral treatment (ART) according to WHO recommendations. The plasma HIV-1 RNA load was measured using the Abbott m2000 RealTime HIV-1 assay. The full-length protease gene and partial reverse transcriptase gene were sequenced, and resistance mutations were assessed by reference to the Stanford University HIV drug resistance database. Of 125 included children (median age, 7 years) taking first-line ART for a median duration of 20 months, 82 (66%) showed detectable HIV-1 RNA load, and 70 (56%) met the 2010 revised WHO criteria of VF (defined as plasma HIV-1 RNA load ≥3.7 log(10) copies/ml). Drug resistance results were available for 52 children with plasma HIV-1 RNA load ≥3.0 log(10) copies/ml, and viruses carrying resistance mutations were found in 48 (92%) children. Among these 48, mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs) or non-NRTIs (NNRTIs) were found in 42 (88%) and 47 (99%) children, respectively. The NRTI-resistant viruses harbored the M184V/I (95%), Q151M (2%), and thymidine-analogue mutations (40%), and the NNRTI-resistant viruses harbored the K103N (34%), Y181C (32%), G190A (23%), and K101E (21%) mutations. A high rate (56%) of VF was demonstrated in Senegalese children after 20 months of first-line ART and therapeutic failure was assessed by the presence of antiretroviral drug resistance mutations in 9 out of 10 children in VF. These findings point out the difficulties of optimizing ART in children living in sub-Saharan Africa, and the crucial need of laboratory monitoring reinforcement.

Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania

“…However, the high virologic failure rate found in our study is comparable with previous reports from similar East and West African settings [9,15,26–30]. Of note, it is significantly lower than the actual national Tanzanian average of 38.8% elaborated by the Tanzanian Chronic Disease Clinic (Ward J, unpublished data), which could be partially attributed to the specialized counsellors and clinicians in our paediatric unit.…”

Extensive Drug Resistance in HIV-Infected Cambodian Children Who Are Undetected as Failing First-Line Antiretroviral Therapy by WHO 2010 Guidelines

“…7,9,10 Children are twice as likely to experience virological failure to ART compared with adults. 11 Furthermore, a large proportion of HIV-infected children (13-53%) are expected to experience virological failure within the first year of treatment and are therefore at a higher risk of developing drug resistance if failure is diagnosed late.…”

“…11 Furthermore, a large proportion of HIV-infected children (13-53%) are expected to experience virological failure within the first year of treatment and are therefore at a higher risk of developing drug resistance if failure is diagnosed late. 7,10,[12][13][14] Such resistance may have important consequences for second-line treatment strategies, particularly in children with reduced treatment options and formularies.…”

The Prediction of Integrase Inhibitors Efficacy in Third Line Regimen after First and Second Line Antiretroviral Therapy Failure in Senegal

“…The second major strain was subtype C in pol gene which is the predominant in MSM group in Senegal [20]. The URF were also found in 17.2% cases similarly described in Senegal [19,21].…”