HIV, which causes acquired immune deficiency syndrome, invades the host cell via the CD4 receptor and CCR5 or CXCR4 co-receptors. Interferons induced early in HIV infection induce an antiviral defense mechanism through IFNAR signaling. Our study aimed to examine the relationship between CCR5, CXCR4, and IFNAR1 gene variations as a risk factor in HIV (+) patients and their response to their clinical parameters. Targeted next-generation sequencing (tNGS) was used to perform molecular genotyping analysis of the CCR5, CXCR4 and IFNAR1 genes in genomic DNA from 22 HIV+ patients and 25 healthy individuals as controls. We detected a total of 13 rare mutations in the study, including 3 missense, 1 synonumous, 2 5′UTR, 4 3′UTR, 1 frameshift variations. We also detected 6 common variants in the IFNAR1 and CXCR4 genes. HIV+ patients carrying the wild type TT genotype of IFNAR1 gene rs2856973 T>A variant had higher CD4+ T cell count compared with patients carrying the TA+AA genotypes of rs2856973 variant in naive and 1st month of ART period (p=0.0011 and p=0.0019, respectively). Similarly, participants receiving ART with TT genotype of rs2856973 showed a significantly higher CD4+ T cell count in the third month (p=0.0008). Patients carrying the homozygous wild type genotype of CXCR4 gene rs2680880 A>T SNP had lower CD4+ T cell count compared with subjects carrying the AT+TT mutant genotypes of rs2680880 in naive and first month period (p=0.0152 and P=0.0256, respectively). Our results demonstrate that variations in the IFNAR1 and CXCR4 genes can contribute to modifications in HIV progression.