Integrase Strand Transfer Inhibitors Resistance-associated Mutations in HIV-infected Pregnant Women

Overview

Journal Rev Esp Quimioter

Specialty Pharmacology

Date 2024 Oct 4

PMID 39364596

Authors

D Cecchini

J Sfalcin

I Zapiola

A Gomez

S Fernandez-Giuliano

C Rodriguez

L Mammana

A Seravalle

F Fay

M C Torroija

G Bugarin

M B Bouzas

Affiliations

Soon will be listed here.

Abstract

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.

References

Salmona M, Lascoux-Combe C, Nere M, Rubenstein E, Molina J, Delaugerre C . Transmission of S230R integrase drug resistance mutation affecting second-generation integrase inhibitors in a French primary HIV-1 infected man. J Antimicrob Chemother. 2023; 78(7):1802-1803. DOI: 10.1093/jac/dkad135. View

Bissio E, Barbas M, Bouzas M, Cudola A, Salomon H, Espinola L . Pretreatment HIV-1 drug resistance in Argentina: results from a surveillance study performed according to WHO-proposed new methodology in 2014-15. J Antimicrob Chemother. 2016; 72(2):504-510. DOI: 10.1093/jac/dkw445. View

Tzou P, Rhee S, Descamps D, Clutter D, Hare B, Mor O . Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance. J Antimicrob Chemother. 2019; 75(1):170-182. PMC: 7850029. DOI: 10.1093/jac/dkz417. View

Inzaule S, Hamers R, Noguera-Julian M, Casadella M, Parera M, Wit T . Primary resistance to integrase strand transfer inhibitors in patients infected with diverse HIV-1 subtypes in sub-Saharan Africa. J Antimicrob Chemother. 2018; 73(5):1167-1172. DOI: 10.1093/jac/dky005. View

Yang Z, Yang X, Deng X, Wei S, Liu J, Ma J . Prevalence of integrase strand transfer inhibitor (INSTIs) resistance mutations in Henan Province, China (2018-2020). Infection. 2021; 49(6):1195-1202. DOI: 10.1007/s15010-021-01668-9. View

Casadella M, Santos J, Noguera-Julian M, Mican-Rivera R, Domingo P, Antela A . Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping. J Antimicrob Chemother. 2020; 75(12):3517-3524. DOI: 10.1093/jac/dkaa349. View

De Salazar A, Vinuela L, Fuentes A, Teyssou E, Charpentier C, Lambert-Niclot S . Transmitted Drug Resistance to Integrase-Based First-Line Human Immunodeficiency Virus Antiretroviral Regimens in Mediterranean Europe. Clin Infect Dis. 2022; 76(9):1628-1635. DOI: 10.1093/cid/ciac972. View

Zapiola I, Cecchini D, Fernandez Giuliano S, Martinez M, Rodriguez C, Bouzas M . [HIV-1 resistance to antiretroviral drugs in pregnant women from Buenos Aires metropolitan area]. Medicina (B Aires). 2016; 76(6):349-354. View

Taylor T, Lee E, Nykoluk M, Enns E, Liang B, Capina R . A MiSeq-HyDRA platform for enhanced HIV drug resistance genotyping and surveillance. Sci Rep. 2019; 9(1):8970. PMC: 6586679. DOI: 10.1038/s41598-019-45328-3. View

10.

Hamers R, Wit T, Holmes C . HIV drug resistance in low-income and middle-income countries. Lancet HIV. 2018; 5(10):e588-e596. DOI: 10.1016/S2352-3018(18)30173-5. View

11.

Luzuriaga K, Mofenson L . Challenges in the Elimination of Pediatric HIV-1 Infection. N Engl J Med. 2016; 374(8):761-70. DOI: 10.1056/NEJMra1505256. View

12.

Arias A, Lopez P, Sanchez R, Yamamura Y, Rivera-Amill V . Sanger and Next Generation Sequencing Approaches to Evaluate HIV-1 Virus in Blood Compartments. Int J Environ Res Public Health. 2018; 15(8). PMC: 6122037. DOI: 10.3390/ijerph15081697. View

13.

Cecchini D, Sfalcin J, Zapiola I, Gomez A, Fernandez Giuliano S, Mammana L . Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. Rev Esp Quimioter. 2021; 34(4):371-375. PMC: 8329568. DOI: 10.37201/req/022.2021. View

14.

Ji H, Patterson A, Taylor T, Rank C, Halverson J, Capina R . Prevalence of Primary Drug Resistance Against HIV-1 Integrase Inhibitors in Canada. J Acquir Immune Defic Syndr. 2018; 78(1):e1-e3. PMC: 5902129. DOI: 10.1097/QAI.0000000000001649. View

15.

Bailey A, Rhee S, Shafer R . Integrase Strand Transfer Inhibitor Resistance in Integrase Strand Transfer Inhibitor-Naive Persons. AIDS Res Hum Retroviruses. 2021; 37(10):736-743. PMC: 8665799. DOI: 10.1089/AID.2020.0261. View

16.

Aulicino P, Zapiola I, Kademian S, Valle M, Fernandez Giuliano S, Toro R . Pre-treatment drug resistance and HIV-1 subtypes in infants from Argentina with and without exposure to antiretroviral drugs for prevention of mother-to-child transmission. J Antimicrob Chemother. 2018; 74(3):722-730. DOI: 10.1093/jac/dky486. View