Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010

Abstract

Transmitted drug resistance (TDR) is a clinical and epidemiological problem because it may contribute to failure of antiretroviral treatment. The prevalence of TDR varies geographically, and its prevalence in Sweden during the last decade has not been reported. Plasma samples from 1,463 patients newly diagnosed with HIV-1 infection between 2003 and 2010, representing 44% of all patients diagnosed in Sweden during this period, were analyzed using the WHO 2009 list of mutations for surveillance of TDR. Maximum likelihood phylogenetic analyses were used to determine genetic subtype and to investigate the relatedness of the sequences. Eighty-two patients showed evidence of TDR, representing a prevalence of 5.6% (95% CI: 4.5%-6.9%) without any significant time trends or differences between patients infected in Sweden or abroad. Multivariable logistic regression showed that TDR was positively associated with men who have sex with men (MSM) and subtype B infection and negatively associated with CD4 cell counts. Among patients with TDR, 54 (68%) had single resistance mutations, whereas five patients had multi-drug resistant HIV-1. Phylogenetic analyses identified nine significantly supported clusters involving 29 of the patients with TDR, including 23 of 42 (55%) of the patients with TDR acquired in Sweden. One cluster contained 18 viruses with a M41L resistance mutation, which had spread among MSM in Stockholm over a period of at least 16 years (1994-2010). Another cluster, which contained the five multidrug resistant viruses, also involved MSM from Stockholm. The prevalence of TDR in Sweden 2003-2010 was lower than in many other European countries. TDR was concentrated among MSM, where clustering of TDR strains was observed, which highlights the need for continued and improved measures for targeted interventions.

Figure 1. Maximum likelihood phylogenetic analysis of study subjects infected with HIV-1 of subtype B.

The upper panel shows the complete tree, which includes sequences from 605 study subjects, 194 MSM diagnosed as HIV-1 infected in Stockholm 1992–2002 , and four subtype B and four subtype D reference sequences (www.hiv.lanl.gov). The tree was generated using partial HIV-1 pol gene sequences using PhyML and the best fitted nucleotide substitution model (i.e. GTR+I+G). Twenty-three codons with resistance mutations were removed from the alignment so that the final alignment contained 987 unambiguously aligned nucleotides. The tree is rooted using the four subtype D reference sequences. Red branches represent sequences with mutations indicative of TDR according to the WHO 2009 list of mutations for surveillance of transmitted drug resistance . Numbers indicate significantly supported (aLRT>0.95) clusters of TDR sequences. The two bottom panels show detailed sub-trees for TDR clusters 1 and 4. The asterisks in the sequence identifiers in cluster 4 indicate that these sequences were obtained from the 1992–2002 dataset . The scale indicates nucleotide substitutions per site.