Determination of Viral Tropism by Genotyping and Phenotyping Assays in Brazilian Hiv-1-Infected Patients

Abstract

The clinical application of CCR5 antagonists involves first determining the coreceptor usage by the infecting viral strain. Bioinformatics programs that predict coreceptor usage could provide an alternative method to screen candidates for treatment with CCR5 antagonists, particularly in countries with limited financial resources. Thus, the present study aims to identify the best approach using bioinformatics tools for determining HIV-1 coreceptor usage in clinical practice. Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects under clinical monitoring were analyzed in this study. Based on the Trofile results, the viral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination of tropism using a Geno2pheno[coreceptor] analysis with a false positive rate of 10% gave the most suitable performance in this sampling: the R5 and X4 strains were found at frequencies of 78.5% and 28.4%, respectively, and there was 78.6% concordance between the phenotypic and genotypic results. Further studies are needed to clarify how genetic diversity amongst virus strains affects bioinformatics-driven approaches for determining tropism. Although this strategy could be useful for screening patients in developing countries, some limitations remain that restrict the wider application of coreceptor usage tests in clinical practice.

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

“…Currently, other CCR5 blockers (e.g., cenicriviroc, leronlimab) are being tested to treat HIV infection and other inflammatory conditions, and maraviroc emerges as a potential drug to treat other diseases involving CCR5, especially some types of cancer (77). In Brazil, CCR5 blockers represent a good choice for HIV treatment, since most of the circulating viral strains show CCR5 tropism (78)(79)(80). Based on the scenario presented above, Figure 1 shown an alluvial diagram representing the classic outcomes associated with the CCR5D32, including "desirable" and "undesirable" effects.…”