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Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients

Article scientifique 2022 Anglais

Résumé

Response to ritonavir-boosted-protease inhibitors (PI/r)-based regimen is associated with some Gag mutations among HIV-1 B-clade. There is limited data on Gag mutations and their covariation with mutations in protease among HIV-1 non-B-clades at PI/r-based treatment failure. Thus, we characterized Gag mutations present in isolates from HIV-1 infected individuals treated with a PI/r-regimen (n = 143) and compared them with those obtained from individuals not treated with PI/r (ART-naïve [n = 101] or reverse transcriptase inhibitors (RTI) treated [n = 118]). The most frequent HIV-1 subtypes were CRF02_AG (54.69%), A (13.53%), D (6.35%) and G (4.69%). Eighteen Gag mutations showed a significantly higher prevalence in PI/r-treated isolates compared to ART-naïve (p < 0.05): Group 1 (prevalence < 1% in drug-naïve): L449F, D480N, L483Q, Y484P, T487V; group 2 (prevalence 1-5% in drug-naïve): S462L, I479G, I479K, D480E; group 3 (prevalence ≥ 5% in drug-naïve): P453L, E460A, R464G, S465F, V467E, Q474P, I479R, E482G, T487A. Five Gag mutations (L449F, P453L, D480E, S465F, Y484P) positively correlated (Phi ≥ 0.2, p < 0.05) with protease-resistance mutations. At PI/r-failure, no significant difference was observed between patients with and without these associated Gag mutations in term of viremia or CD4 count. This analysis suggests that some Gag mutations show an increased frequency in patients failing PIs among HIV-1 non-B clades.

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Této, G., Nka, A., Fokam, J., Bouba, Y., Takou, D., Fabeni, L., Carioti, L., Armenia, D., Semengue, E., Dambaya, B., Sosso, S., Colizzi, V., Perno, C., Ceccherini‐Silberstein, F., Santoro, M., Ndjolo, A. (2022). Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. https://doi.org/10.1038/s41598-022-05375-9

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Auteur(s)

Georges Této Alex Durand Nka Joseph Fokam Yagaï Bouba Désiré Takou Lavinia Fabeni Luca Carioti Daniele Armenia Ezéchiel Ngoufack Jagni Semengue Béatrice Dambaya Samuel Martin Sosso Vittorio Colizzi Carlo Federico Perno Francesca Ceccherini‐Silberstein Maria Mercedes Santoro Alexis Ndjolo

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