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The APOBEC3G gene is one of the most important host factors thathas beenfound previously associated withHIV infection and AIDS progression. The host's susceptibility to viral infectionmay be influenced by any APOBEC3G genetic variation.The main aim of thecurrent study was to investigate the association of three SNPs in the APOBEC3G gene (rs8177832, rs35228531, and rs2294367) respectively, with disease outcomes in Moroccan HIV-1 infected patients. A case-control study was conducted in 194 HIV-1 infected patients and 195 healthy controls and the three selected APOBEC3G SNPs were genotyped in all participants using TaqMan® allelic discrimination assays. The rs2294367 CG genotype was found strongly associated with the protection profile against the HIV-1 infection (OR=0.44, 95% CI=0.28-0.67, p=0.0002). The rs2294367 CG genotype (p=0.0009) was found as a protective element while the rs2294367 GG genotype (p=0.015) has shown susceptibility against HIV-1 infection among females. Furthermore, the rs2294367CG genotype seemed to protect older subjects (>50 years) from infection (p=0.001). Haplotype analysis demonstrated that the GCC haplotype from (rs8177832, rs35228531, and rs2294367) observed could be associated with a high risk of HIV-1 infection in Morocco, OR=2.25, 95% CI=1.12-4.49, p=0.022). This study demonstrates significant associations between the studied polymorphisms in APOBEC3G with pVL variations during treatment. Thus, our findings confirm that genetic variations in the APOBEC3G gene might modulate the susceptibility to HIV-1 infection and the response to antiviral drugs in Moroccan individuals. However, it should be noted that the main limitation of this study is the moderate sample size, thus a validation study with a larger sample is warranted., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)