Coreceptor Usage of Human Immunodeficiency Virus Type 1 Strains in Ibadan, Nigeria

Abstract

Aims: To evaluate HIV-1 Coreceptor usage in Nigeria. Study Design: Cross-sectional study. Place and Duration of Study: Department of Virology, College of Medicine, University College Hospital, Ibadan from January 2004 to December 2006. Methodology: Genomic DNA was extracted from blood samples of 85 (42 males, 43 females; age range 18-58 years) consenting HIV-1 infected antiretroviral therapy-naïve individuals presenting at a voluntary counseling and testing centre. The env C2-V3 region of HIV-1 proviral DNA was amplified by nested PCR, successfully sequenced, manually edited and evolutionary relationships determined by maximum likelihood using MEGA 5.03R from 64 of the blood samples of the HIV-1 infected patients. HIV-1 coreceptor usage was predicted based on genotypic analysis of HIV-1 env V3 loop sequences. Results: Phylogenetic analysis showed HIV-1 subtypes A, G, CRF02_AG, CRF06_cpx, and CRF35_AD among the study participants The V3 loop region of the viruseshad amino acid sequence conservation in the base positions 1-8 and 26-35 and tip regions and sequence variability, including mutations and deletions at positions 9-25. Most (76.6%) of the sequences had the GPGQ crown motif while the GPGQ/L/R/K substitution was observed in 18.8%. The number of N-linked glycosylation sites ranged from 0 to 4 per env C2-V3 amino acid sequence with only 37.5% of the sequences having all 4 N-linked glycosylation sites. Predicted frequencies for CCR5 and CXCR4 genotypes were 31.2% and 68.8%, respectively, while 10% of the CCR5-tropic viruses showed Maraviroc-associated resistant mutations. Conclusion: CXCR4-tropic viruses predominate among the studied population irrespective of HIV-1 subtype and and it is associated with multiple amino acid deletions and mutations in V3 and the loss of one or more N-linked glycosylation sites. This data suggest the need for further studies involving a larger sample size prior to introduction of coreceptor inhibitors like Maraviroc for management of HIV infection in Nigeria