Rapid emergence of primary mutations associated with antiretroviral drug resistance in HIV-infected children under HAART

M VIGNOLES, G BARBONI, M AGOSTI,, J QUARLERI, M GARCÍA, V GIRAUDI, S GONZÁLEZ AYALA, H SALOMÓN

Sydney, Australia

Conferencia; 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2007

International AIDS Society

Objectives: To evaluate the emergence of viral strains with antiretroviral drug resistance mutations in children receiving HAART. Methods: Forty recently diagnosed HIV-perinatally infected children who initiated HAART were evaluated. Ninety percent of these children and their mothers had not received ART; 4 children had received AZT during 6 weeks after birth. Samples were collected before and during ART. The therapeutic regimens used were: AZT/3TC or 3TC/D4T plus NFV or NVP. Standard sequencing of pol gene and further drug resistance analysis were performed. Selective real-time PCR was performed to detect up to 0.1% of M184V carrying strains. Results: All except one of the children had wild-type viruses (by population sequencing) at baseline. Throughout treatment 70% (28/40) of them selected viral strains with at least one primary mutation associated with ART resistance. These were: K103N, Y181C, G190A, V106A, M184V, M41L, conferring resistance to all available NNRTIs and several NRTIs. Selection of M184V mutation was clearly the most frequent (100%) being also detected as a minor population at baseline in 3 patients. This mutation appears later by conventional genotyping in an average time of 3.6 months under therapy. Resistance developed in a median time of 5.5 months (1-19 months) after ART initiation. Conclusions: A high percentage of mutations associated with ART resistance emerged shortly after HAART initiation in children who had been mostly infected with wild-type viruses. The low percentage of cases with previous presence of minority lamivudine-resistant variants can not explain the rapid resistance emergence, being poor adherence to therapy or deficient drug bioavailability, the most probable causes. This work stresses the need in Argentina of continuous monitoring of viral drug resistance and specially ART adherence (considering the implementation of directly observed treatment) in children under HAART to make successful treatments more likely.