CCR5 promoter SNP genotype in HIV seropositive infants on combinational antiretroviral therapy in Uganda: Association with virological failure

Abstract

IntroductionBy Sept 2018, only 59.3% of all HIV positive children on cART under 5 years were achieving virological suppression compared to 88.4% in the general population in Uganda. CCR5 promoter genotype specifically single nucleotide polymorphisms have been linked to modulate patient virological status. However, the few studies that have studied the association in infants have utilized allele-specific PCR a genotypic method limited to detecting already known SNPs. By using Sanger sequencing, we explored the association taking into account novel mutations. Methods Following ethical approvals, a cross sectional study was conducted using archived buffy coat samples from a pediatric HIV drug resistance study between May 2019 and January 2022 at the Joint Clinical Research Centre in Kampala, Uganda. 100 HIV seropositive infant buffy coat samples were sequenced for CCR5 SNP genotype following nucleic acid extraction, polymerase chain reaction and sanger sequencing. Odds ratios were used to determine the association between CCR5 SNPs and infant HIV plasma loads. Results 10 SNPs were identified with frequencies as follows; 58227G/A (21.8%), 58636A/G (28.7%), 58934T/G (74.7%), 59029G/A (48.3%), 59353T/C (55.2%), 59356C/T (23.0%), 59402G/A (94.2%) 59653C/T (66.7%), 59802A/C (34.5%), and 60024A/G (34.5%). Notably, 58227G/A, 58636A/G, 59802A/C, and 60024A/G are novel SNPs. However, none of these SNPs was significantly associated with infant virological failure but SNPs 59029G/A and 59353T/C showed higher odds of occurring in non-suppressors whereas 59356C/T and 59402G/A appeared to correlate with reduced plasma HIV loads. Infant virological suppression remained at 59% and in agreement with the national data. Conclusion Our study augments previous studies that CCR5 promoter SNPs play a role in modulating patient virological status however, strong conclusions could be drawn from either utilizing in-vitro studies or large epidemiological studies.