No transmitted drug resistance to HIV integrase strand-transfer inhibitors after their scale-up in Estonia in 2017.

OBJECTIVES: In Eastern Europe, HIV-1 transmitted drug resistance (TDR) data, especially in the integrase (IN) region, are limited. In Estonia, INSTI (integrase strand transfer inhibitors) TDR has been studied only prior to the INSTI scale-up in late 2010s. The current study aimed to determine the levels of protease (PR), reverse transcriptase (RT) and IN surveillance drug resistance mutations (SDRMs) among newly diagnosed patients in Estonia in 2017. METHODS: The study included 216 newly diagnosed HIV-1 individuals from 1 January until 31 December 2017 in Estonia. Demographic and clinical data were obtained from the Estonian Health Board, the Estonian HIV Cohort Study (E-HIV) and clinical laboratories' databases. The PR-RT and IN regions were sequenced and analysed for SDRMs and subtype determination. RESULTS: Seventy-one percent (151/213) of available HIV-positive samples were successfully sequenced. The overall level of TDR was 7.9% (12/151; 95% CI 4.4%-13.8%); no dual or triple class resistance was detected. No major INSTI mutations were found. The distribution of SDRMs for NNRTI, NRTI and PI was 5.9% (9/151), 1.3% (2/151) and 0.7% (1/151), respectively. The predominant NNRTI mutation was K103N. CRF06_cpx was the predominant variant (59%) in the Estonian HIV-1 population, followed by subtype A (9%) and subtype B (8%). CONCLUSION: Although no major INSTI mutations were found, close monitoring of INSTI SDRMs is needed considering the extensive use of the first- and second-generation INSTIs. PR-RT TDR is slowly rising in Estonia, indicating the need for continuous surveillance in the future. Low genetic barrier NNRTIs should be avoided in the treatment regimens.

Stable level of HIV transmitted drug resistance in Estonia despite significant scale-up of antiretroviral therapy.

BACKGROUND: Due to the widespread use of non-nucleoside reverse transcriptase inhibitors (NNRTI) as part of first-line therapies to curb the human immunodeficiency virus (HIV) epidemic in Eastern-European countries, transmitted drug resistance (TDR) is of serious concern in this region. Therefore, TDR and its associated risk factors were investigated among newly diagnosed HIV-1 subjects in Estonia. METHODS: This nationwide observational study included all newly diagnosed HIV-1 subjects from January 1 until December 31, 2013. Demographic and clinical data were collected using the national surveillance system and the Estonian HIV-positive patient database (E-HIV). Starting from RNA, the HIV-1 protease (PR) and reverse transcriptase (RT) region was sequenced and surveillance drug resistance mutations (SDRM) were determined. Sequences from previous studies in Estonia and from public databases were included to study epidemic trends and to determine TDR clusters by phylogenetic analysis. RESULTS: Out of 325 newly diagnosed HIV-1 infections, 224 were successfully sequenced (68%). As in previous studies from Estonia, the circulating recombinant form CRF06_cpx was the most prevalent HIV subtype (164/224, 74%). Fifteen strains displayed SDRM, giving a TDR rate of 6.7% (95% CI 3.9; 11.0). The most common SDRMs were associated with NNRTI (10/15, 4.5%), followed by PI (3/15, 1.3%) and NRTI (2/15, 0.9%). K103 N (8/15, 53%) was the most common SDRM. The level of TDR and mutational patterns were comparable to previous years. Twenty-six transmission clusters containing Estonian sequences were observed, of which 23/26 belonged to CRF06_cpx and 2/26 displayed evidence of TDR. The only risk factor associated with the presence of TDR was imprisonment (OR 5.187, CI 1.139-25.565, p = 0.034). CONCLUSIONS: TDR remained stable at a moderate level in Estonia, K103N is the main SDRM with only one transmission-pair detected. We suggest screening for TDR at the time of diagnosis or prior to antiretroviral treatment initiation to tailor first-line regimens accordingly. SUMMARY: The third consecutive transmitted drug resistance (TDR) study demonstrated a stable TDR in Estonia. TDR reached 6.7% (moderate level) in 2013, with imprisonment being the only associated risk factor. Few drug resistance-associated transmission clusters were identified.