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Abstract
High rate of nelfinavir-associated mutations observed among women exposed to prophylactic antiretroviral during pregnancy
F.M. Kakehasi, U. Tupinanmbas, S. Cleto, A. Aleixo, E. Lin, V. Melo, R. Aguiar, J. Pinto, Maternal and Pediatric AIDS Group
Federal University of Minas Gerais, Maternal and Pediatric AIDS Group, Belo Horizonte, Brazil
Objectives: To assess the presence of resistance mutations in women exposed to ART for PMTCT after 6 months post-delivery.
Methods: Genotypic resistance testing was performed in 30 isolates from women exposed to prophylactic ART during pregnancy. All women discontinued ART after labor. Genotype tests were performed in two time points: before or during ART (T1) and after ART discontinuation (T2). Follow-up visits were performed 6 weeks and 6 months post-partum.
Results: Of the 30 women studied, 63.4% received ZDV+3TC +NFV, 23.3% ZDV+3TC +NVP and 13.3% ZDV only. The median viral load at third trimester was 5,515 copies/mL. HIV subtype B was the most prevalent (70%), followed by subtype F (20%), D/F (3.3%) and D/B/F (3.3%). All infants were uninfected. Median maternal viral load and CD4 counts in T2 were 10,616 copies/mL and 545 cells/mL, respectively. High polymorphism rate at protease gene was found at T1 (53 mutations), one patient had major mutation (M46I) and another naïve patient showed multi-PI and NRTI-associated mutations. Analysis on transcriptase reverse gene at T1 showed one patient with M184V (which persisted on T2), and two (6.9%) with NNRTI resistance mutation (G190A). New nelfinavir-associated mutations were observed in T2 in 5 out of 19 (26.1%) patients exposed to this drug: N88S (3/19), D30N + N88D (1/19) and L90M (1/19). No new NNRTI resistant mutation (K103N or Y181C) was observed and only one (3.3%) patient presented NRTI resistant mutation (V118I) in T2.
Conclusions: In this group of women ART regimens were very efficient to block MTCT, despite the partial virologic suppression. The finding of a high rate of nelfinavir resistant mutation observed in the post-partum period may impact future therapeutic options for these women.
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