Genetic Polymorphism in the Ccr5-delta32 Allele and the Role of Mobile Technology in Evaluating Hiv Drug Resistance

Abstract

More than 37 million individuals are infected with the human immunodeficiency virus (HIV), and numerous people die from HIV-related illnesses annually. Although HIV prevalence and patterns vary by nation, the occurrences of HIV in high-risk populations vary by category. CCR5Δ32 is a non-destructive gene caused by deletion of 32 base pairs on Cysteine-Cysteine Chemokine Receptor 5 (CCR5). The allele protects its homozygous carriers from HIV infection while slows disease progression to its heterozygous carriers. This study aimed at determining the genetic polymorphism in the CCR5-Delta32 allele through in silico approach and promotes the use of mobile technology in evaluating HIV drug resistance. A systematic review and meta-analysis of published studies was carried out and results used in this study to show a comparison of the allele spread between different populations. CCR5Δ32 related sequences were downloaded and grouped according to geographical regions for further analysis. Analysis, visualization and presentation was done using Unipro Ugene bioinformatics software in combination with other free online bioinformatics tools. For mutation detection, SNP discovery, allele identification, and sequence confirmation, the core receptor regions of HIV sequences were subjected to a similarity search through the Basic Local Alignment Search Tool and assembled against HIV-1 reference sequences. The pol protein region was trimmed and compared to a template in the Stanford database (https://hivdb.stanford.edu/), then used to create an Android mobile application (ARVPredictor) capable of interpreting HIV drug resistance and anti-retroviral drug interactions. Three geographical regions; Europe, Africa, and Asia were categorized from the 37 studies reviewed with a total of 17,535 participants. Caucasians made up 44.7% of the population, Africans 17.8% and Asians 19.3%. With a pooled Odds Ratio (OR) of 0.08 (95% CI, 0.06 - 0.10, P < 0.00001), test of subgroup differences at I2 = 47.0%, and a P value of 0.13, the distribution of the CCR5Δ32 allele among different populations in comparison to its heterozygosity showed a significant association. Caucasians had a subtotal OR of 0.07 (95% CI, 0.05 - 0.10, I2 = 82%) and a significant P value of < 0.00001, indicating high level of CCR5Δ32 homozygosity, compared to Asians with an OR of 0.14 (95% CI, 0.05 - 0.37, I2 = 31%) and Africans with an OR of 0.27 (95% CI, 0.04 – 1.69).A strong indication that race can be a factor in determining CCR5Δ32 homozygosity or heterozygosity, and that Caucasians are more likely to be homozygous of the allele. Similarly, when compared to the Stanford HIV Database, the developed ARVPredictor identified similar HIV subtypes in 98/100 sequences during test performance (kappa - 0.98 – near perfect agreement). ARVPredictor identified 89/100 major NNRTI and NRTI mutations that were similar to those found in the Stanford HIV Database (kappa - 0.89 – near perfect agreement). This study reports a novel tool that accurately identifies HIV-1 drug resistance mutations that targets the HIV pol gene, and provides appropriate antiretroviral drugs for use at the point of care. It takes advantage of and utilizes today’s high-speed data networks as well as smartphone accessibility.