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. 2024 Dec;37(6):479-485.
doi: 10.37201/req/074.2024. Epub 2024 Oct 4.

Integrase strand transfer inhibitors resistance-associated mutations in HIV-infected pregnant women

D Cecchini  1 , J Sfalcin, I Zapiola, A Gomez, S Fernandez-Giuliano, C Rodriguez, L Mammana, A Seravalle, F Fay, M C Torroija, G Bugarín, M B Bouzas
Affiliations

Integrase strand transfer inhibitors resistance-associated mutations in HIV-infected pregnant women

D Cecchini et al. Rev Esp Quimioter. 2024 Dec.

Abstract
in English, Spanish

Objective: To date, no data exist regarding the prevalence of integrase inhibitor (INSTI) resistance-associated mutations (HIVDRM) in HIV-infected pregnant women (HPW) in Latin America. We describe the prevalence and transmissibility of integrase HIVDRM in a historical cohort of INSTI-naïve HPW from Argentina (n=56) with Next Generation Sequencing (NGS).

Methods: Bioinformatics analysis was performed by HyDRA software for 20%, 10%, 5%, 2%, and 1% sensitivity thresholds. We calculated the mutational viral load for each INSTI-HIVDRM, considering those with >1000 c/mL as of high risk of transmissibility.

Results: The predominant HIV subtype was BF (78.5%). Major HIVDRM were not detected with the population sequencing 20% filter. With a 1% threshold, the prevalence increased to 8.9%; Y143C/S, E92G, E138K, and T66I mutations were found. The median (range) mutational load (expressed in c/mL) was: 355 (50.2-11705); with only 1 case >1000 c/mL Accessory mutations (G163R/K, T97A) were detected mostly with a 20% sensitivity threshold with an overall prevalence of 23.2%; the median (IQR) mutational load was: 23929 (4009-63158) c/mL; all of them above 1000 c/mL.

Conclusions: Our results show evidence of the presence of major INSTI-HIVDRM as aleatory mutations and a high frequency of accessory mutations with potential transmissibility in HPW.

Objetivo: Hasta la fecha, no existen datos sobre la prevalencia de mutaciones asociadas a la resistencia (HIVDRM) a los inhibidores de la integrasa (INSTI) en mujeres embarazadas infectadas por VIH (HPW) en América Latina. Describimos la prevalencia y la transmisibilidad de las HIVDRM de la integrasa en una cohorte histórica de HPW naive de INSTI de Argentina (n=56) mediante Next Generation Sequencing (NGS).

Material y métodos: Se realizó un análisis bioinformático mediante el software HyDRA para umbrales de sensibilidad del 20%, 10%, 5%, 2% y 1%. Calculamos la carga viral mutacional para cada INSTI-HIVDRM, considerando aquellas con >1000 c/mL como de alto riesgo de transmisibilidad.

Resultados: El subtipo de VIH predominante fue BF (78,5%). No se detectaron HIVDRM principales con el filtro de secuenciación poblacional del 20%. Con un umbral del 1%, la prevalencia aumentó al 8,9%; se encontraron las mutaciones Y143C/S, E92G, E138K y T66I. La mediana (rango) de la carga mutacional (expresada en c/mL) fue: 355 (50,2-11705); con solo 1 caso >1000 c/mL. Las mutaciones accesorias (G163R/K, T97A) se detectaron principalmente con un umbral de sensibilidad del 20%, con una prevalencia general del 23,2%; la media-na (RIQ) de la carga mutacional fue: 23929 (4009-63158) c/mL; todas ellas por encima de 1000 c/mL.

Conclusión: Nuestros resultados muestran evidencia de la presencia de INSTI-HIVDRM principales como mutaciones aleatorias y una alta frecuencia de mutaciones accesorias con potencial transmisibilidad en HPW.

Keywords: HIV; integrase inhibitors; mutations; pregnant women; prevalence.

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Conflict of interest statement

DC participated in educational activities organized by MSD (travel grant, speaker fees). Rest of authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart describing the inclusion of stored samples (period 2008-2014) from HIV-infected pregnant women for a baseline survey of resistance to integrase inhibitors (INSTI) by next-generation sequencing in Argentina. Pr/RT: protease inhibitor/reverse transcriptase inhibitor; cDNA: complementary DNA
See this image and copyright information in PMC

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