Low prevalence of doravirine-associated resistance mutations among polish human immunodeficiency-1 (HIV-1)–infected patients

2021 ◽  
pp. 135965352110430
Author(s):  
Kaja Scheibe ◽  
Anna Urbańska ◽  
Paweł Jakubowski ◽  
Maria Hlebowicz ◽  
Monika Bociąga-Jasik ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Treatment ◽  
Transcriptase Inhibitor ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Genetic Barrier ◽  
Nnrti Resistance ◽  
Treatment Naïve ◽  
Low Prevalence ◽  
Hiv 1

Introduction Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) that retains activity against common NNRTI resistance mutations. In this study, we aimed to investigate the prevalence of DOR resistance mutations compared with that of resistance mutations for other NNRTIs among HIV-1-infected treatment‐experienced and -naïve patients from Poland. Methods Resistance to DOR and other NNRTIs was assessed in two datasets: 1760 antiretroviral treatment-naïve HIV-1 patients and 200 treatment‐experienced patients. All 1960 sequences were derived from the patients using bulk sequencing. For resistance analyses, Stanford HIV drug resistance database scores were used. Results Overall, DOR resistance was present in 32 patients (1.62%), of whom 13 (0.74%) were naïve and 19 (9.50%) were treatment-experienced. The most common DOR resistance mutations observed among the naïve patients were A98G and K101E (0.2% each), and those among cART-experienced patients were L100I (2.0%), K101E, V108I, H221Y, and P225H (1.5% each). Furthermore, among the naïve patients, less common resistance to DOR (0.7%) compared with that to nevirapine (NVP) (2.1%; p = 0.0013) and rilpivirine (5.40%; p < 0.0001) was observed. For sequences obtained from treatment-experienced patients, the frequency of resistance to DOR (9.5%) was lower than that for efavirenz (25.5%; p < 0.0001) and NVP (26.0%; p < 0.0001). Conclusions The frequency of transmitted drug resistance to DOR is low, allowing for effective treatment of antiretroviral treatment-naïve patients and rapid treatment initiation. In cART-experienced patients, this agent remains an attractive NNRTI option with a higher genetic barrier to resistance.

Diversity of HIV-1 subtypes and transmitted drug-resistance mutations among minority HIV-1 variants in a Turkish cohort

2021 ◽  
Vol 19 ◽  
Author(s):  
Rabia Can Sarinoglu ◽  
Uluhan Sili ◽  
Ufuk Hasdemir ◽  
Burak Aksu ◽  
Guner Soyletir ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Treatment Naïve ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

Background: The World Health Organization (WHO) recommends the surveillance of transmitted drug resistance mutations (TDRMs) to ensure the effectiveness and sustainability of HIV treatment programs. Objective: Our aim was to determine the TDRMs and evaluate the distribution of HIV-1 subtypes using and compared next-generation sequencing (NGS) and Sanger-based sequencing (SBS) in a cohort of 44 antiretroviral treatment-naïve patients. Methods: All samples that were referred to the microbiology laboratory for HIV drug resistance analysis between December 2016 and February 2018 were included in the study. After exclusions, 44 treatment-naive adult patients with a viral load of >1000 copies/mL were analyzed. DNA sequencing for reverse transcriptase and protease regions was performed using both DeepChek ABL single round kit and Sanger-based ViroSeq HIV-1 Genotyping System. The mutations and HIV-1 subtypes were analyzed using the Stanford HIVdb version 8.6.1 Genotypic Resistance software, and TDRMs were assessed using the WHO surveillance drug-resistance mutation database. HIV-1 subtypes were confirmed by constructing a maximum-likelihood phylogenetic tree using Los Alamos IQ-Tree software. Results: NGS identified nucleos(t)ide reverse transcriptase inhibitor (NRTI)-TDRMs in 9.1% of the patients, non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI)-TDRMs in 6.8% of the patients, and protease inhibitor (PI)-TDRMs in 18.2% of the patients at a detection threshold of ≥1%. Using SBS, 2.3% and 6.8% of the patients were found to have NRTI- and NNRTI-TDRMs, respectively, but no major PI mutations were detected. M41L, L74I, K65R, M184V, and M184I related to NRTI, K103N to NNRTI, and N83D, M46I, I84V, V82A, L24I, L90M, I54V to the PI sites were identified using NGS. Most mutations were found in low-abundance (frequency range: 1.0% - 4.7%) HIV-1 variants, except M41L and K103N. The subtypes of the isolates were found as follows; 61.4% subtype B, 18.2% subtype B/CRF02_AG recombinant, 13.6% subtype A, 4.5% CRF43_02G, and 2.3% CRF02_AG. All TDRMs, except K65R, were detected in HIV-1 subtype B isolates.. Conclusion: The high diversity of protease site TDRMs in the minority HIV-1 variants and prevalence of CRFs were remarkable in this study. All minority HIV-1 variants were missed by conventional sequencing. TDRM prevalence among minority variants appears to be decreasing over time at our center.

PREVALENCE AND STRUCTURE OF HIV-1 DRUG RESISTANCE AMONG TREATMENT NAÏVE PATIENTS SINCE THE INTRODUCTION OF ANTIRETROVIRAL THERAPY IN THE RUSSIAN FEDERATION

2019 ◽  
Vol 11 (2) ◽  
pp. 75-83 ◽  
Author(s):  
A. A. Kirichenko ◽  
D. E. Kireev ◽  
A. E. Lopatukhin ◽  
A. V. Murzakova ◽  
I. A. Lapovok ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Russian Federation ◽  
Antiretroviral Drugs ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Treatment Naïve ◽  
The Russian Federation ◽  
Hiv 1

Aim: to analyze the prevalence, structure of drug resistance and drug resistance mutations in the protease and reverse transcriptase genes of HIV-1 among treatment naïve patients.Materials and methods. We analyzed protease and reverse transcriptase sequences from 1560 treatment naïve HIV-infected patients from all Federal Districts of the Russian Federation with the first positive immune blot during 1998–2017. Sequences were analyzed for the presence of drug resistance mutations and predicted drug resistance to antiretroviral drugs using two algorithms — Stanford HIVDR Database (HIVdb) and the 2009 SDRM list (CPR).Results. The prevalence of drug resistance mutations was 11,1%. More often the prevalence of drug resistance was found for non-nucleoside reverse transcriptase inhibitor drugs (rilpivirine, nevirapine, efavirenz). The prevalence of transmitted drug resistance associated with mutations from the SDRM list was 5,3%, which is classified by the WHO as a moderate level. However, it should be noted that since the large-scale use of antiretroviral drugs in the Russian Federation, there has been a trend towards a gradual increase in the level of the transmitted drug resistance, and in 2016 it has already reached 6,1%.Conclusion. The results demonstrate the need for regular surveillance of the prevalence of HIV drug resistance to antiretroviral drugs among treatment naïve patients in the Russian Federation.

Frequency of Transmitted Drug Resistance Mutations Among Treatment-Naïve HIV-1-Infected Individuals at a Tertiary Care Centre in South India

2015 ◽  
Vol 19 (5) ◽  
pp. 273-275 ◽  
Author(s):  
Rajesh Kannangai ◽  
Shoba David ◽  
Vijayanand C. Sundaresan ◽  
Jaiprasath Sachithanandham ◽  
Monika Mani ◽  
...  
Keyword(s):  
Drug Resistance ◽  
South India ◽  
Tertiary Care ◽  
Transmitted Drug Resistance ◽  
Care Centre ◽  
Resistance Mutations ◽  
Tertiary Care Centre ◽  
Drug Resistance Mutations ◽  
Treatment Naïve ◽  
Hiv 1

HIV-1 Genetic Diversity and Transmitted Drug Resistance in Antiretroviral Treatment-Naive Individuals from Amapá State, Northern Brazil

2016 ◽  
Vol 32 (4) ◽  
pp. 373-376 ◽  
Author(s):  
Lindomar dos Anjos Silva ◽  
Flavia Divino ◽  
Márlisson Octávio da Silva Rêgo ◽  
Ivina Geselle Lima Lopes ◽  
Cláudia Maria Nóbrega Costa ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Antiretroviral Treatment ◽  
Transmitted Drug Resistance ◽  
Treatment Naïve ◽  
Northern Brazil ◽  
Hiv 1

scholarly journals Transmitted drug resistance and transmission clusters among HIV-1 treatment-naïve patients in Guangdong, China: a cross-sectional study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yun Lan ◽  
Linghua Li ◽  
Xiang He ◽  
Fengyu Hu ◽  
Xizi Deng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Cross Sectional ◽  
Genetic Transmission ◽  
Treatment Naïve ◽  
Hiv 1

Abstract Background Transmitted drug resistance (TDR) that affects the effectiveness of the first-line antiretroviral therapy (ART) regimen is becoming prevalent worldwide. However, its prevalence and transmission among HIV-1 treatment-naïve patients in Guangdong, China are rarely reported. We aimed to comprehensively analyze the prevalence of TDR and the transmission clusters of HIV-1 infected persons before ART in Guangdong. Methods The HIV-1 treatment-naïve patients were recruited between January 2018 and December 2018. The HIV-1 pol region was amplified by reverse transcriptional PCR and sequenced by sanger sequencing. Genotypes, surveillance drug resistance mutations (SDRMs) and TDR were analyzed. Genetic transmission clusters among patients were identified by pairwise Tamura-Nei 93 genetic distance, with a threshold of 0.015. Results A total of 2368 (97.17%) HIV-1 pol sequences were successfully amplified and sequenced from the enrolled 2437 patients. CRF07_BC (35.90%, 850/2368), CRF01_AE (35.56%, 842/2368) and CRF55_01B (10.30%, 244/2368) were the main HIV-1 genotypes circulating in Guangdong. Twenty-one SDRMs were identified among fifty-two drug-resistant sequences. The overall prevalence of TDR was 2.20% (52/2368). Among the 2368 patients who underwent sequencing, 8 (0.34%) had TDR to protease inhibitors (PIs), 22 (0.93%) to nucleoside reverse transcriptase inhibitors (NRTIs), and 23 (0.97%) to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Two (0.08%) sequences showed dual-class resistance to both NRTIs and NNRTIs, and no sequences showed triple-class resistance. A total of 1066 (45.02%) sequences were segregated into 194 clusters, ranging from 2 to 414 sequences. In total, 15 (28.85%) of patients with TDR were included in 9 clusters; one cluster contained two TDR sequences with the K103N mutation was observed. Conclusions There is high HIV-1 genetic heterogeneity among patients in Guangdong. Although the overall prevalence of TDR is low, it is still necessary to remain vigilant regarding some important SDRMs.

scholarly journals Identifications of drug resistance mutations among antiretroviral treatment naive HIV-1 patients in Peninsular Malaysia

2017 ◽  
Vol 10 (1) ◽  
pp. 75-78
Author(s):  
Rozainanee Mohd Zain ◽  
Nabila Ibrahim ◽  
Suriani Ismail ◽  
Jeyanthi Suppiah ◽  
Nor Aziyah Mat Rahim ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Treatment ◽  
Peninsular Malaysia ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Treatment Naïve ◽  
Hiv 1

scholarly journals The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China

2020 ◽  
Vol 148 ◽  
Author(s):  
Min Chen ◽  
Qiongmei Zhu ◽  
Hui Xing ◽  
Huichao Chen ◽  
Xiaomei Jin ◽  
...  
Keyword(s):  
Public Health ◽  
Drug Resistance ◽  
Transcriptase Inhibitor ◽  
People Living With Hiv ◽  
Resistance Mutations ◽  
Public Health Response ◽  
Nnrti Resistance ◽  
Health Response ◽  
Western Yunnan ◽  
Hiv 1

Abstract HIV-1 drug resistance can compromise the effectiveness of antiretroviral therapy (ART). A survey of pretreatment HIV-1 drug resistance (PDR) was conducted in Lincang Prefecture of Yunnan Province. From 372 people living with HIV/AIDS initiating ART for the first time during 2017–2018, 322 pol sequences were obtained, of which 11 HIV-1 strain types were detected. CRF08_BC (70.2%, 226/322) was the predominant strain, followed by URF strains (10.6%, 34/322). Drug resistance mutations (DRMs) were detected among 34.2% (110/322) of the participants. E138A/G/K/R (14.3%, 46/322) and V179E/D/T (13.7%, 47/322) were the predominant DRMs. Specifically, E138 mutations commonly occurred in CRF08_BC (19.9%, 45/226). Among the DRMs detected, some independently conferred resistance, such as K65R (1.6%, 5/322), Y188C/F/L (0.9%, 3/322), K103N (0.6%, 2/322) and G190A (0.3%, 1/322), which conferred high-level resistance. The prevalence of PDR was 7.5% (95% CI: 4.6–10.3%) and the prevalence of non-nucleotide reverse transcriptase inhibitor (NNRTI) resistance was 5.0% (95% CI: 2.6–7.4%), which is below the threshold (⩾10%) of initiating a public health response. In conclusion, HIV-1 genetic diversity and an overall moderate level of PDR prevalence were found in western Yunnan. PDR surveillance should be continually performed to decide whether a public health response to NNRTI resistance should be initiated.

scholarly journals Prevalence of transmitted drug resistance among HIV-1 treatment-naive patients in Beijing

2018 ◽  
Vol 146 (3) ◽  
pp. 339-344 ◽  
Author(s):  
Y.X. Song ◽  
R.L. Xin ◽  
Z.C. Li ◽  
H.W. Yu ◽  
W.H. Lun ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Frequent Mutations ◽  
Treatment Naïve ◽  
Sex With Men ◽  
Hiv 1

AbstractTo optimise patients’ outcomes and gain insight into transmitted drug resistance (TDR) among human immunodeficiency virus (HIV)-1 treatment-naive patients in Beijing, the prevalence of TDR was assessed. Demographic and clinical data of 1241 treatment-naive patients diagnosed between April 2014 and February 2015 were collected. TDR was defined using the Stanford University HIV drug resistance mutations database. The risk factors were evaluated by multi-logistic regression analysis. Among 932 successfully amplified cases, most were male (96.78%) and infected through men having sex with men (91.74%). Genotype were CRF01_AE (56.44%), B (20.60%), CRF07_BC (19.96%), C (1.61%) and other genotypes (1.39%). The overall prevalence of TDR was 6.12%. Most frequent mutations occurred in non-nucleoside reverse transcriptase inhibitors (NNRTIs) (3.11%), followed by protease inhibitors (PIs) (2.25%) and nucleoside reverse transcriptase inhibitors (NRTIs) (1.32%). Furthermore, HIV-1 genotype was associated with high risk of resistance, in which genotype C and other genotype may have higher risk for resistance. The prevalence among treatment-naive patients in Beijing was low. Resistance to NNRTIs was higher than with PIs or NRTIs. Continuous monitoring of regional levels of HIV-1 TDRs would contribute to improve treatment outcomes and prevent failures.

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