P04. Effect of dolutegravir in combination with NRTI in HIV-1 infected individuals with pre-existing NRTI-mutations

Erik Sörstedt1, Christina Carlander 2, Leo Flamholc3, Bo Hejdeman4, Veronica Svedhem-Johansson5, Anders Sönnerborg5, 6, Magnus Gisslén1, Aylin Yilmaz1
Affiliates: 1Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 413 90 Gothenburg, Sweden; 2Centre for Clinical Research, County Hospital Västerås, 721 89 Västerås, Sweden; 3Department of Infectious Diseases, Malmö University Hospital, 205 02 Malmö, Sweden; 4Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet and Unit of Infectious Diseases / Venhälsan, Södersjukhuset, SE-118 83 Stockholm, Sweden; 5Department of Infectious Diseases, Karolinska Institute, Karolinska University Hospital, 141 86 Stockholm, Sweden; 6Department of Clinical Microbiology, Karolinska Institute, Karolinska University Hospital, 141 86 Stockholm, Sweden.

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Background
People living with HIV (PLWH) with nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations have had few other options than regimens based on ritonavir-boosted protease inhibitors (PI/r) until the introduction of dolutegravir. Here we report the virologic results from PLWH in Sweden with pre-existing NRTI-mutations on treatment with dolutegravir and 1–2 NRTIs.

Methods
All Swedish PLWH on treatment with dolutegravir and 1–2 NRTIs > 4 weeks and with pre-existing NRTI-mutations were retrospectively identified from the national InfCare HIV database. As controls we included PLWH on PI/r and 1–2 NRTIs, matched according to Genotypic Susceptibility Score (GSS). Median CD4 was 473/570 cells/μL among participants/controls and HIV RNA <1.30 log10 copies/ml in both groups. Virologic failure was defined as an HIV RNA increase from a previously supressed level ( 200 copies/mL for treated participants or never suppressed to < 50 copies/mL for naïve individuals or those starting treatment after an interruption.

Results
In total, 197 participants (median age 50 years, 62% male) and 197 controls were included. Median observation time was 35 weeks (interquartile range (IQR) 21–54). Five participants and seven controls had viral failure resulting in success rates of 97.5% and 96.4%, respectively. The most prevalent pre-existing NRTI mutations were at positions M184 (27% of all samples), T215 (12%), and D67 (10%). Median (IQR) GSS was 2 (1.5–3.0) for both participants and controls.

Conclusions
Dolutegravir in combination with 1–2 NRTIs was as efficient as PI/r in individuals with pre-existing NRTI mutations. Even though follow-up was shorter for participants on dolutegravir than PI/r, we consider dolutegravir a solid alternative to PI/r-based antiretroviral therapy also in the presence of NRTI-resistance.