Primary resistance to integrase strand transfer inhibitors in patients infected with diverse HIV-1 subtypes in sub-Saharan Africa

Inzaule, SC; Hamers, RL; Noguera-Julian, M; Casadellà, M; Parera, M; Rinke de Wit, TF; Paredes, R

Journal article

Primary resistance to integrase strand transfer inhibitors in patients infected with diverse HIV-1 subtypes in sub-Saharan Africa

Abstract:: Objectives To investigate the prevalence and patterns of major and accessory resistance mutations associated with integrase strand transfer inhibitors (INSTIs), across diverse HIV-1 subtypes in sub-Saharan Africa.

Methods pol gene sequences were obtained using Illumina next-generation sequencing from 425 INSTI-naive HIV-infected adults from Kenya (21.2%), Nigeria (7.3%), South Africa (22.8%), Uganda (25.2%) and Zambia (23.5%). Drug resistance interpretation was based on the IAS 2017 mutation list and accessory mutations from Stanford HIVdb with resistance penalty scores of ≥10 to at least 1 INSTI. Resistance was further classified based on sensitivity thresholds of ≥20% (Sanger sequencing) and 1%–20% for low-frequency variants (next-generation sequencing).

Results Of 425 genotypes, 48.7% were subtype C, 28.5% A, 10.1% D, 2.8% G and 9.9% were recombinants. Major INSTI resistance mutations were detected only at <20% threshold, at a prevalence of 2.4% (2.5% in subtype A, 2.4% C, 0% D, 8.3% G and 2.4% in recombinants) and included T66A/I (0.7%), E92G (0.5%), Y143C/S (0.7%), S147G (0.2%) and Q148R (0.5%). Accessory mutations occurred at a prevalence of 15.1% at the ≥20% threshold (23.1% in subtype A, 8.7% C, 11.6% D, 25% G and 23.8% in recombinants), and included L74I/M (10.4%), Q95K (0.5%), T97A (4%), E157Q (0.7%) and G163R/K (0.7%).

Conclusions Major INSTI resistance mutations were rare and only occurred at low-level resistance detection thresholds. INSTI-based regimens are expected to be effective across the different major HIV-1 subtypes in the region.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Inzaule, S. C., Hamers, R. L., Noguera-Julian, M., Casadellà, M., Parera, M., Rinke de Wit, T. F., & Paredes, R. (2018). Primary resistance to integrase strand transfer inhibitors in patients infected with diverse HIV-1 subtypes in sub-Saharan Africa. Journal of Antimicrobial Chemotherapy, 73(5), 1167–1172.

MLA Style

Inzaule, SC, et al. “Primary Resistance to Integrase Strand Transfer Inhibitors in Patients Infected with Diverse HIV-1 Subtypes in Sub-Saharan Africa.” Journal of Antimicrobial Chemotherapy, vol. 73, no. 5, 2018, pp. 1167–72.

Chicago Style

Inzaule, SC, RL Hamers, M Noguera-Julian, et al. 2018. “Primary Resistance to Integrase Strand Transfer Inhibitors in Patients Infected with Diverse HIV-1 Subtypes in Sub-Saharan Africa.” Journal of Antimicrobial Chemotherapy 73 (5): 1167–72.
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