Emmi Andersson (1,2), Johanna Brännström(3), Göran Bratt(4), Aylin Yilmaz(5), Jan Albert(2,6), Anders Sönnerborg(1,2,3,7)

Affiliates

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden(1), Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden(2), Unit of Infectious Diseases, Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden(3), Department of Clinical Science and Education, Södersjukhuset, Karolinska Institute, Stockholm, Sweden(4), Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden(5), Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden(6), of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden(7)

Abstract

Background
The Swedish HIV-1 epidemic is diverse and shaped by migration from high endemic countries and transmission among men having sex with men (MSM) both in Sweden and abroad. Roll-out of pre-exposure prophylaxis in Sweden and introduction of dolutegravir-based ART in low-income countries calls for continuous vigilance of drug resistant HIV-1 in Sweden with the addition of integrase strand inhibitors and potentially minor viral variants. An important aim for the prospective, multicenter TIME-study is to continue a detailed investigation of the prevalence and characteristics of HIV-1 drug resistance in Sweden.
Methods
This analysis includes the first 60 individuals included in the TIME study from November 1st 2017 until July 31st 2018. All individuals presenting for HIV-1 care for the first time in Sweden at the study clinics Karolinska, Venhälsan and Sahlgrenska were screened. All naïve individuals and those on ART prescribed abroad with incomplete viral suppression, were eligible. A questionnaire provided detailed data such as migration date, earlier ART, and evidence of primary HIV-1 infection. The national research database InfCareHIV provided epidemiological data and biomarkers including population based pol sequences obtained at diagnosis through routine genotypic resistance testing (GRT). Next generation deep sequencing (NGS) was performed on base-line plasma for analysis of resistance in minor viral variants (results not yet available).
Results
So far, 60 individuals were included (Karolinska 36; Venhälsan 12; Sahlgrenska 12). Male: 46 (77%); female: 14 (23%). Median age: 41 years (range 19-73). Transmission routes: heterosexual n=32 (53%), MSM n=25 (42%), intravenous drug use n=3 (5%). 27 (45%) were born in Sweden and 33 (55%) were of non-Swedish origin (n=13 (22%) from Sub-Saharan Africa (SSA), n= 5 (8%) from South East Asia, n=15 (25%) of other origin). The proportion of migrants was 65% in those heterosexually infected compared to 40% in MSM. The most common reported country of transmission was Sweden, n=18 (30%), followed by Thailand n=10 (17%), sub-Saharan Africa n=8 (13%). In n=19 (32%) other countries were reported and n=5 (8%) had missing data. In MSM 9/25 (36%) had reported transmission in Sweden. A diverse HIV-1 subtype distribution was found; CRF01_AE n=13, B n=12, C n=8, CRF02_AG n=6, n=14 other subtypes/recombinants. For 11 (18%) patients the HIV-1 diagnosis was known before arriving to Sweden of whom 6 patients (10%) reported ART exposure before arrival. In 4 of these exposed patients GRT was available.
In 53 patients, GRT for PR and RT at baseline was available. In 7 (13.2%), pretreatment drug resistance (PDR) was detected. Four reported previous ART exposure and three were ART naïve. In the ART exposed patients 3/4 had clinically significant resistance to NRTI and/or NNRTI. In the non-exposed, 1/3 had clinically significant resistance to both NRTI and NNRTI. No protease inhibitor mutations were found. In 34 individuals routine GRT for integrase was available. In one patient E157Q, with unclear significance was found.
Conclusions
Our preliminary results confirm the diversity of the Swedish HIV-epidemic and a high rate of PDR against NRTI and/or NNRTI. Travel and migration impacts and a substantial proportion of transmissions abroad is reported in both Swedish-born and migrants, but Sweden is the most common reported country of transmission. Not surprisingly individuals on failing regimens infected and treated abroad are prone to have PDR.