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Abstract:

Background: Cyprus has one of the lowest HIV prevalence in Europe. According to the ECDC, there were 794 reported cases in 2012, of which around 400 were individuals who reside or used to reside permanently in Cyprus. Since 2011, the number of newly diagnosed individuals has increased. Herein, we aimed to determine the prevalence and time trends of subtypes and the factors associated with their onward transmission in Cyprus. Materials & Methods: 335 consenting study subjects were recruited from the AIDS Clinic of Larnaca General Hospital between 2003 and 2012. The genetic subtypes of the circulating HIV-1 strains were determined by REGAv3, COMETv1.0 and manual phylogenetic analysis. The HIV-1 sequence identified for each study subject was analyzed by BLAST and the 30 best-matched sequences were used as controls for the transmission cluster (TC) analysis. Maximum likelihood trees were constructed by RAxMLv8.2.1. TCs were identified using a genetic distance of <0.045 and 98% bootstrap support as thresholds and confirmed by Bayesian phylogenetic analyses (BEAST). Statistical analyses were performed by R. Results: 54% of the study subjects were infected with subtype B, followed by A1 (20%), C (9%), CRF02_AG (6%) and F1 (6%). There were no significant time trends in the distribution of subtypes in newly diagnosed individuals (n=204). 86% of the study subjects infected with subtype B and 57% of the study subjects with subtype A were Cypriots. However, only 48% of the Cypriot study subjects infected with subtype B and 61% of those infected with subtype A reported to have been infected in Cyprus. There were no significant differences in the distribution of HIV-1 subtypes between the cities of residence within Cyprus. Subtype B strains were more frequent (69%) among men who have sex with men (MSM) whereas non-B subtypes were more frequent (53%) among heterosexuals. Transmission cluster analysis identified 47 TCs, 20 of which consisted of 3 or more patients. 83% (43/52) of study subjects were in subtype B TCs compared to only 54% (13/24) in subtype A TC (p<0.001). Additionally, 14 subtype B pairs were identified, as well as 6 pairs for A1, 4 for C, 1 for F and 3 for CRF02AG. Within the subgroup of TC ≥3, 13 clusters were subtype B, 4 were subtype A, 1 was subtype C and 1 was CRF02AG. However, 93% of the pairs and all the TC ≥3 originated before 2008. Within the later, 4 clusters originated in 2004 and included a large number of Cypriots (n=12), mainly MSM individuals infected with subtype B. Male gender, MSM and Cypriot origin factors were significantly associated with TCs of subtype B in the univariate analysis. However, MSM was the single factor associated with HIV transmission clusters according to the multivariate analysis. On the other hand, none of the factors was significantly associated with transmission of subtype A. Conclusions: Onward transmission of subtype B in Cyprus is associated with the MSM population, as in other European countries, whereas any of the factors were associated with the transmission of subtype A.