The temporal increase in HIV‐1 non‐R5 tropism frequency among newly diagnosed patients from northern Poland is associated with clustered transmissions

CCR5 (R5) tropic viruses are associated with early stages of infection, whereas CXCR4 (X4) HIV‐1 tropism has been associated with severe immunodeficiency. We investigated the temporal changes in the genotype‐predicted tropism frequency and the phylogenetic relationships between the R5 and non‐R5 clades. Methods A cohort of 194 patients with a newly diagnosed HIV infection that was linked to their care from 2007 to 2014 was analyzed. Baseline plasma samples were used to assess the HIV‐1 genotypic tropism with triplicate V3‐loop sequencing. The non‐R5 tropism prediction thresholds were assigned using a false positive rate (FPR) of 10 and 5.75% and associated with clinical and laboratory data. The transmission clusters were analyzed using pol sequences with a maximum likelihood and Bayesian inference. Results The overall non‐R5 tropism frequency for 5.75% FPR was 15.5% ( n= 30) and 27.8% ( n= 54) for 10% FPR. The frequency of the non‐R5 tropism that was predicted using 5.75% FPR increased significantly from 2007 (0%) to 2014 ( n= 5/17, 29.4%) ( p= 0.004, rough slope +3.73%/year) and from 0% (2007) to 35.3% (2014, n= 6/17) ( p= 0.071, rough slope +2.9%/year) using 10% FPR. Increase in the asymptomatic diagnoses over time was noted ( p =0.05, rough slope +3.53%/year) along with a tendency to increase the lymphocyte CD4 nadir ( p =0.069). Thirty‐two clusters were identified, and non‐R5 tropic viruses were found for 26 (30.95%) sequences contained within 14 (43.8%) clusters. Non‐R5 tropism was associated with subtype D variants ( p =0.0001) and the presence of CCR5 Δ32/wt genotype ( p =0.052). Conclusions R5 tropism predominates among the treatment of naive individuals, but the increases in the frequency of non‐R5 tropic variants may limit the clinical efficacy of the co‐receptor inhibitors. The rising prevalence of non‐R5 HIV‐1 may indicate transmission of X4 clades.