Najwa Alaoui1,2, Moulay Abdelaziz El Alaoui3,4,5, Hicham El Annaz3,6, Fatima Zahra Farissi3,6, Amine Sanaâ Alaoui3,4, Elmostapha El Fahime3,4, Saad Mrani3,6,7. 1. Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco, alaouin2000@yahoo.fr. 2. Research Team in Molecular Virology and Oncobiology, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco, alaouin2000@yahoo.fr. 3. Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco. 4. Molecular Biology and Functional Genomics Platform, National Center for Scientific and Technical Research, Rabat, Morocco. 5. Laboratory of Genetics and Biometry, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco. 6. Research Team in Molecular Virology and Oncobiology, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco. 7. National Reference Laboratory, Mohammed VI University of Science, Casablanca, Morocco.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: This study demonstrated that INSTIs should be an excellent alternative for salvage therapy in highly experienced patients with multidrug resistant viruses in Morocco.
BACKGROUND: We aimed to analyze for the first time in Morocco the integrase (IN) sequence variability among highly experienced HIV-1-infectedpatients with no prior IN strand transfer inhibitor (INSTI) exposure who failed on reverse transcriptase inhibitors and protease inhibitors. METHODS: 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. RESULTS: 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. CONCLUSION: This study demonstrated that INSTIs should be an excellent alternative for salvage therapy in highly experienced patients with multidrug resistant viruses in Morocco.