Introduction Paediatric HIV-1 infection remains an important public health issue in resource-limited settings. In Brazil, the access to combined antiretroviral therapy (cART) and the HIV-1 genotyping test are available for all infected children and adolescents. However, mainly due to low patient adherence, multidrug-resistant (MDR) viruses have been increasing over the last years. This study estimate the resistance associated to the new generation protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the possible use in rescue strategies for children and adolescents failing cART.
Methods Between 2008 and 2014, blood samples from 246 HIV-1-infected children and adolescents failing different cART regimens, were collected in the Rio de Janeiro State, Brazil. The profiles of HIV-1 resistance mutations were evaluated in the Stanford website and subtype confirmed by phylogeny.
Results The majority of genotyped samples were classified as HIV-1 subtype B (75.6%), followed by subtype F1 (15.4%), BF recombinants (4.1%), subtype C (3.3%) and subtype A1, CRF_02AG and the recombinant A1B in one subject each. A total of 31.2% of patients showed resistance associated to first line therapy, 45.3% for the second line and 23.4% to third line. MDR mutations were detected in only 3% of the children. The prevalence of PI-associated mutations was low (3.6%), except for the M46I/L mutation (24.4%) associated to the majority of PIs. The resistance to PIs used in the rescue therapies, were 2.8% for the darunavir and 3.6% for the tipranavir. High prevalence of thimidine associated mutations (TAMs) and to lamivudine, were observed (>80%). But, mutations to the nucleotide reverse transcritptase inhibitor (NRTI) Tenofovir, showed low prevalence (5.3%). In addition, resistance mutations associated to the decrease of a virological response to etravirine were 5.4% and 3.8% to rilpivirine.
Conclusion Low prevalence of drug resistance mutations associated to the new generation of PIs and NNRTIs was observed in our genotyping database. The impact of resistance mutations under darunavir seems lower than for tipranavir in children failing other PI-based regimens. Although prior failure to other PIs or NNRTI might produce cross-resistance, the results show that all of these drugs used in the therapy rescue, could be effective and constitute a good option for children who failure other regimens.