HIV population genotypic tropism testing and its clinical significance

HIV co-receptor tropism testing is recommended before therapy when the C-C chemokine receptor type 5 antagonist maraviroc is initiated. This review addresses the use of population genotypic tropism testing in relation to clinical practice.

Genotypic tropism tests predict viral co-receptor tropism based on the sequence of the V3 loop of the viral envelope. HIV occurs in a swarm of variants in the patient's body, called quasispecies. As next-generation sequencing techniques are not generally accessible to date, triplicate testing is often performed to improve sensitivity of population-based approaches, but no prospective studies assessing the performance of single and triplicate procedures related to clinical outcome have been performed yet. For interpretation of the genotype several web-based algorithms have been developed. Varying the cut-off of the commonly used geno2pheno[co-receptor] algorithm changes the sensitivity and specificity of the tropism prediction. In retrospective analyses of clinical studies and cohorts genotypic population tropism testing demonstrated equal correlation with clinical outcome on maraviroc compared with phenotypic assays.In patients with suppressed viraemia, proviral DNA testing is a well tolerated alternative to HIV-RNA testing.

Population genotypic methods have greater accessibility, lower cost, and faster turnaround time than other methods. Despite limited sensitivity for minority variants HIV genotypic population tropism testing showed good correlation with clinical outcome.