OBJECTIVES: To evaluate the relative diagnostic performance of genotypic sequencing and enhanced-sensitivity phenotypic testing methods for: i) identifying the tropism of HIV-1 infected patients, and ii) predicting virological response to CCR5-antagonist therapy. METHODS: A systematic review of the literature (via EMBASE and Medline databases) initially identified 359 publications. Based on a priori defined eligibility criteria, five studies were included in the final analysis.   RESULTS: Four of the five studies assessed the diagnostic performance of genotypic testing in identifying viral tropism, with the enhanced-sensitivity Trofile assay (ESTA) as the reference standard. Using the geno2pheno bioinformatic algorithm, genotypic testing maintained a high concordance with ESTA (range: 70.6%‑85.3%). At a false-positive rate (FPR) of 5%, specificity for R5-tropic virus was also high (range: 85.7%‑95.3%), but came at the expense of sensitivity for X4-using virus (range: 36.7%‑66.7%). One study compared the effectiveness of both genotypic tropism testing and ESTA in predicting virological response to the CCR5-antagonist maraviroc. The study found in each screening group, a similar proportion of patients achieved a viral load < 50 HIV-1 RNA copies/mL by Week 48. CONCLUSIONS: In the absence of a ‘gold standard’, clinical response to CCR5-anatagonist therapy offers the best measure of diagnostic performance in HIV-1 tropism testing. The results of this review indicate that genotypic sequencing of the V3 loop is as capable of predicting response to CCR5-antagonist therapy as the current diagnostic standard, ESTA. In addition, of the bioinformatic algorithms reviewed here, the geno2pheno model set at 5-10% FPR offered the best balance between sensitivity and specificity. This evidence provides further support for the use of genotypic tropism testing in routine clinical practice.