High prevalence of CXCR4 using HIV-1 strains as predicted by genotypic tools among recently infected antiretroviral naïve individuals and among subtype C strains in Southern Brazil
Background: Specificity of HIV-1 coreceptor usage for CCR5 or CXCR4 is believed to be dictated mainly by the V3 loop's structure and charge. Understanding the tropism of circulating strains is critical for the therapeutic use of CCR5 antagonists, disease natural history comprehension and prediction of disease progression. This study analyzed the coreceptor tropism of HIV-1 subtypes B, C and BC recombinants of drug naïve individuals from Rio Grande do SuL through genotypic tools.
Methods: Stored plasma specimens from 81 patients, enrolled on Project Ampliar, known to be infected with subtypes B (30), C (25) or BC (26) recombinants based on RT and PR sequences along the pol gene were selected. After nested PCR, the V3 region of env gene was sequenced and the tropism inferred using genotypic methods: Raymond's Rule, Geno2pheno coreceptor 5% and 10%, WebPSSMX4R5, SINSI(B), SINSI(C), R5/X4-Pred and NSI/SI-Pred. A sample was considered as CXCR4 tropic strain if any of genotypic tools classified as such, otherwise it was considered R5.
Results: Forty-seven (58%) individuals were men, 15 (18.5%) were recent seroconverters and 78 (96.3%) reported sexual exposure. Subtypes found at env region were 36 B (44.4%) and 45 C (55.6%). The overall prevalence of R5 viruses was 71.6%. Considering the subtypes from both pol and env regions, CXCR4 usage was predicted in 28.6% of BC recombinants, 31% of B and 25% of C. CXCR4 tropic strains proportions among subtypes from env region, which determines the tropism, were 33.3% for B and 24.4% for C (no statistical difference, p=0.263). X4 prevalence in recent seroconverters was 33.3%. There was no association between tropism and viral load.
Conclusion: Significant prevalence of CXCR4 tropic strains (28.4%) was found among drug naïve HIV-1 infected individuals from southern Brazil, including recent seroconverters and subtype C, which has been previously associated to infrequent transition from R5 to X4 strains.
A.C. Vanni1,2, L.R. Motta1, R.D. Sperhacke1, S.K. Kato1,3,4, R.S. Diaz5, J.A.B. Chies2
1Universidade de Caxias do Sul, Laboratório de Pesquisa em HIV/AIDS (LPHA), Caxias do Sul, Brazil, 2Universidade Federal do Rio Grande do Sul - UFRGS, Laboratório de Imunogenética, Porto Alegre, Brazil, 3Pontifícia Universidade Católica do Rio Grande do Sul, Departamento de Estatística, Porto Alegre, Brazil, 4Fundação Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil, 5Universidade Federal de São Paulo, Laboratório de Retrovirologia, São Paulo, Brazil