HIV-1 Integrase Resistance among Highly Antiretroviral Experienced Patients from Morocco

Abstract

<b><i>Background:</i></b> We aimed to analyze for the first time in Morocco the integrase (IN) sequence variability among highly experienced HIV-1-infected patients with no prior IN strand transfer inhibitor (INSTI) exposure who failed on reverse transcriptase inhibitors and protease inhibitors. <b><i>Methods:</i></b> The HIV-1 IN region was sequenced from plasma samples of all 78 recruited patients. The amino acid IN sequences were HIV-1 subtyped and screened for the presence of polymorphisms against the HxB2 clade B consensus sequence by the geno2pheno subtyping tool and interpreted for drug resistance according to the Stanford algorithm. <b><i>Results:</i></b> The viral subtypes were subtype B (88.4%), CRF02_AG (8.9%), CRF01_AE (1.28%), and subtype C (1.28%). The major INSTI resistance mutations at positions 66, 92, 118, 138, 140, 143, 147, 148, 155, and 263 were absent, while two accessory mutations, L74M/I, known to have no clinical impact to INSTIs in the absence of the major resistance mutations, were detected in three samples (3.84%; two CRF02_AG and one CRF01_AE). Others specific substitutions with an uncertain role on the HIV-1 susceptibility to INSTIs at positions 72, 101, 119, 124, 156, 165, 193, 201, 203, 206, 230, 232, and 249 were found to be relatively common. <b><i>Conclusion:</i></b> This study demonstrated that INSTIs should be an excellent alternative for salvage therapy in highly experienced patients with multidrug resistant viruses in Morocco.

Prevalence of resistance mutations associated with integrase inhibitors in therapy-naive HIV-positive patients in Baoding, Hebei province, China

“…In this study, many amino acid polymorphisms that are different from the standard B subtype strains were detected in both the CRF01_AE and CRF07_BC strains, which have also been reported in untreated persons who are infected with other genotype strains in other countries ( Brado et al, 2018 ; Alaoui et al, 2019 ; Huang et al, 2019 ; Lai et al, 2021 ). Although these polymorphic variants were encountered in more than half of the studied participants, other polymorphic mutations that probably have no effect on INSTIs susceptibility were reported in previous in vitro studies, and clinical trials showed different frequencies ( Kobayashi et al, 2011 ; Casadellà et al, 2015 ).…”

Current Progress in Genomic and Genetic Research on Human Viral Diseases

“…In this study, many amino acid polymorphisms that are different from the standard B subtype strains were detected in both the CRF01_AE and CRF07_BC strains, which have also been reported in untreated persons who are infected with other genotype strains in other countries (Brado et al, 2018;Alaoui et al, 2019;Lai et al, 2021). Although these polymorphic variants were encountered in more than half of the studied participants, other polymorphic mutations that probably have no effect on INSTIs susceptibility were reported in previous in vitro studies, and clinical trials showed different frequencies (Kobayashi et al, 2011;Casadellà et al, 2015).…”

A computational overview of integrase strand transfer inhibitors (INSTIs) against emerging and evolving drug-resistant HIV-1 integrase mutants

“…A month later, the viral load was undetectable, and after about 8 months, a pair of novel mutations T97A and S147G in IN were detected (Wainberg and Han 2015b , a ). These outcomes propose that DTG should be used with caution in INSTI salvage therapy for RAL failures or in patients with multiple RAMs (Alaoui et al 2019 ).…”