Integrase Strand Transfer Inhibitor (INSTI) Genotypic Resistance Analysis in Treatment-Naive, INSTI Free Antiretroviral-Experienced and INSTI-Experienced Turkish Patients Infected with HIV-1.

BACKGROUND AND OBJECTIVE: Integrase strand transfer inhibitors (INSTIs) are currently the standard of practice for first-line HIV therapy for most patients. We evaluated the mutations associated with INSTI resistance in naive HIV-1 infected patients and treated them with antiretrovirals (ART). METHODS: The study, conducted in the 2018 - 2020 period, included 50 ART-naïve patients, 69 INSTI free ART-experienced patients, and 82 INSTI-experienced patients. INSTI resistance mutations were interpreted using the Stanford University HIVdb Program algorithm. RESULTS: INSTI resistance was not detected in ART naïve patients. At least one INSTI resistance mutation was detected in 10% of the INSTI-free patients and 29% of the INSTI-treated patients. Major INSTI-mutations E138K, Y143R, S147G, Q148R, N155H, and E157Q were found in raltegravir. Additional mutations, E92Q, E138K, G140A, S147G, and Q148R were found in elvitegravir; E192Q, E138K/T, G140A/S, S147G, Q148H/R, N155H, E157Q were found in dolutegravir (DTG) experienced patients. According to all drug classes, drug resistance mutation prevalences were determined at the rate of 60%, 46%, and 46% in the RAL, EVG, and DTG groups, respectively. CONCLUSION: Our findings provide data for treatment and resistance management of INSTIs and may provide feedback for INSTIs resistance surveillance consensus-building efforts. In viral rebound under INSTI treatment, INSTI-resistant mutations follow typical INSTI resistance pathways and high resistance rates. INSTI resistance genotypic analysis should be considered before any DTG-based regimes can be initiated in the future, and reduced DTG susceptibility should be carefully monitored and investigated.

Comparative Evaluation of the Treatment of COVID-19 with Multicriteria Decision-Making Techniques.

Objectives: The outbreak of coronavirus disease 2019 (COVID-19) was first reported in December 2019. Until now, many drugs and methods have been used in the treatment of the disease. However, no effective treatment option has been found and only case-based successes have been achieved so far. This study aims to evaluate COVID-19 treatment options using multicriteria decision-making (MCDM) techniques. Methods: In this study, we evaluated the available COVID-19 treatment options by MCDM techniques, namely, fuzzy PROMETHEE and VIKOR. These techniques are based on the evaluation and comparison of complex and multiple criteria to evaluate the most appropriate alternative. We evaluated current treatment options including favipiravir (FPV), lopinavir/ritonavir, hydroxychloroquine, interleukin-1 blocker, intravenous immunoglobulin (IVIG), and plasma exchange. The criteria used for the analysis include side effects, method of administration of the drug, cost, turnover of plasma, level of fever, age, pregnancy, and kidney function. Results: The results showed that plasma exchange was the most preferred alternative, followed by FPV and IVIG, while hydroxychloroquine was the least favorable one. New alternatives could be considered once they are available, and weights could be assigned based on the opinions of the decision-makers (physicians/clinicians). The treatment methods that we evaluated with MCDM methods will be beneficial for both healthcare users and to rapidly end the global pandemic. The proposed method is applicable for analyzing the alternatives to the selection problem with quantitative and qualitative data. In addition, it allows the decision-maker to define the problem simply under uncertainty. Conclusions: Fuzzy PROMETHEE and VIKOR techniques are applied in aiding decision-makers in choosing the right treatment technique for the management of COVID-19.

NS5A resistance - associated substitutions in chronic hepatitis C patients with direct acting antiviral treatment failure in Turkey.

OBJECTIVES: Chronic hepatitis C (CHC) is now a more curable disease with new direct acting antivirals (DAA). Although high sustained virologic response rates, failures still occur in DAA regimens. Our objective in this study was to characterize the real-life presence of clinically relevant resistance - associated substitutions (RASs) in the HCV NS5A gene in CHC patients whose DAA regimen has failed. METHODS: The study enrolled 53 CHC patients who experienced failure with DAA regimen as the prospective longitudinal cohort between 2017-2019. Genotypic resistance testing was performed via the viral population sequencing method and The Geno2pheno HCV tool was used for RAS analysis. RESULTS: The most frequent failure category was relapse (88%) followed by non-responder (12%). For a total of 36% of patients, RASs was detected in NS5A, Y93H was the most detected RAS in GT1b infected patients (89%). CONCLUSIONS: This study establishes an HCV failure registry for Turkey in which samples were combined with clinical, virologic and molecular data of adult patients whose DAA therapy failed. RASs can occur in CHC patients with DAA treatment failures. Evaluation of RAS after DAA failure is very important before re-treatment is initiated to prevent virologic failure.