P23-19. Increasing prevalence of transmitted drug resistance mutations in migrants from Sub Saharan Africa diagnosed with HIV-1 in Sweden

Emmi Andersson [1,3], Agnes Nordquist [2], Joakim Esbjörnsson [2,4,5], Leo Flamholc [6], Magnus Gisslén [7], Bo Hejdeman [8], Hans Norrgren [10], Veronica Svedhem [9,11], Jan Albert [2,3], Anders Sönnerborg [1,3,9,11]
Affiliates: [1] Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. [2] Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. [3] Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden. [4] Nuffield Department Medicine, University of Oxford, Oxford, United Kingdom. [5] REGA Institute, Katholieke Universiteit, Leuven, Belgium. [6] Department of Infectious Diseases, Skane University Hospital, Malmo, Sweden. [7] Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden. [8] Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Sweden. [9] Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden. [10] Department of Clinical Sciences Lund, Lund University, Lund, Sweden. [11] Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.

Background
Since the introduction of modern antiretroviral regimens, prevalence of transmitted drug resistance (TDR) has been reported as stable or decreasing in Europe. In an earlier study in Sweden 2003 – 2010 the prevalence of TDR was 5.6%. Recently, WHO reports increasing prevalence of transmitted and pre-treatment drug resistance to non-nucleoside transcriptase inhibitor (NNRTI) -drugs in Sub-Saharan Africa (SSA), especially in East Africa. Many patients diagnosed with HIV-1 in Sweden are migrants from this high-endemic area.

Methods
All adult antiretroviral therapy-naïve patients diagnosed with HIV-1 in Sweden 2010-2016 were included. Patient data and pol sequences were extracted from the national InfCare HIV database. TDR was defined as the presence of surveillance drug resistance mutations. A CD4+ T-cell decline trajectory model was used to estimate the time of infection. Phylogenetic inference was used for subtyping and cluster identification. Chi-square tests and logistic regressions were used to determine associations between TDR and epidemiological and viral factors.

Results
1,713 pol sequences were analysed, corresponding to 71% of all diagnosed patients during the study period, of whom 53% were heterosexuals and 34% men who have sex with men (MSM). The overall prevalence of TDR was 7.1% (95% CI: 5.8% – 8.3%). NNRTI TDR increased significantly from 1.5% in 2010 to 6.2% in 2016, and was associated with infection/origin in SSA. Phylogenetic inference did not show extensive clustering of non-B TDR strains and CD4-trajectory analysis did not support spread of TDR HIV-1 within Sweden in migrants from SSA. A MSM transmission cluster dating back to the 1990´s with the M41L mutation was also identified. Twenty-five (1.5%) patients exhibited TDR to tenofovir (TDF) (n=8) and/or emtricitabine/lamivudine (FTC/3TC) (n=9 and n=8, respectively) of whom 6 were MSM and 12 migrants from SSA.

Conclusions
The prevalence of TDR increased from 2010 to 2016 in HIV-1 infected migrants from SSA diagnosed in Sweden, mirroring the situation in this region. TDR to TDF/FTC used in pre-exposure prophylaxis confirms a clinical and epidemiological need for resistance testing in newly diagnosed patients.