4%) were subtype B, with a higher rate in the MSM group (n = 183; 93.8%) (Table 1). DRMs were found in a total of 38 patients among the 266 sequences tested (14.3%). There was a constant increase in mutation rate Selleck Ivacaftor (P = 0.001 for trend): while there

were no resistance mutations between 2001 and 2005 (n = 35), there were 14.3% in 2006 (n = 14), 9.5% in 2007 (n = 42), 11.4% in 2008 (n = 61) and 21.9% in 2009 (n = 114). Resistance mutations were exclusively from the MSM ERC. Excluding two subtype A viruses, all DRMs were subtype B viruses. Within the mutated viruses, 18 (6.8%) harboured nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated resistance mutations, with K103N being the most abundant; 15 (5.6%) had protease inhibitor (PI)-associated mutations; and three (1.1%) had nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations. One virus had

two classes (NNRTI and PI) and another virus harboured three classes of associated resistance mutations. Although not statistically significant (P = 0.66), in 2009 we documented a switch in the abundance of mutations as PI DRMs became more frequent than NNRTI DRMs (11.4% vs. 8.7%, respectively). Phylogenetic analysis carried out on a total of 198 subtype B sequences identified two major clusters of DRMs (Fig. 1a). One of the identified clusters included 13 of the 14 viruses harbouring the L90M major Alectinib PI-resistance mutation grouped together with a bootstrap support of 100%. Eleven patients within this cluster were diagnosed in 2009, one in 2008 and one in 2006.

The low evolutionary distance between these sequences and their pattern of segregation suggest a single source of infection RVX-208 (Fig. 1b). The second cluster included 12 of 17 viruses harbouring the K103N NNRTI-associated resistance mutation (Fig. 1c). We further looked into the laboratory characteristics and response to cART of patients infected with the L90M viruses. A large range of viral loads and CD4 counts were found at baseline (989–100 000 HIV-1 RNA copies/ml and 150–760 cells/μl, respectively). Seven of the clustered L90M-infected patients started cART. One of the three patients who were treated with efavirenz and tenofovir/emtricitabine failed to suppress the viral load and rapidly developed the K103N resistance mutation in RT despite good adherence. In contrast, two others responded well to the same regimen. Four patients were given a higher genetic barrier regimen, for example darunavir. Three of them maintained their viral load below 40 copies/ml, but one failed to suppress the viral load below 40 copies/ml. Similar to previous reports from other industrialized countries and Israel [4, 13-16], the data presented herein demonstrate an increasing rate of DRMs in the treatment-naïve population in Tel Aviv, mainly in the MSM ERC.