Higher Frequency of HIV-1 Drug Resistance and Increased Nucleoside Reverse Transcriptase Inhibitor Mutations among the HIV-1 Positive Antiretroviral Therapy–Naïve patients Coinfected With Mycobacterium tuberculosis Compared With Only HIV Infection in India

Background: Emergence of human immunodeficiency virus (HIV) drug resistance mutations prior to highly active antiretroviral therapy is a serious problem in clinical management of HIV/AIDS. Risk factors for appearance of drug resistance mutations are not known. We hypothesize that Mycobacterium tuberculosis infection may contribute to rapid emergence of such mutations in antiretroviral therapy–naïve patients. Methods: A total of 115 patients were recruited in this study of which 75 were HIV+TB+ coinfected (group 1) and 40 were HIV+TB− (group 2). Blood samples from all the patients were collected and CD4+ cell counts; HIV-1 plasma viral load and sequencing of protease and two-third region of reverse transcriptase of HIV-1 was performed and analyzed for drug resistance pattern. Results: For patients with HIV+TB+, 10.6% (8/75) had mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs), 4% (3/75) to nucleoside reverse transcriptase inhibitors, and only 2.6% (2/75) patients had mutations to protease inhibitors. Interestingly, for group 2 (HIV+TB−), there were only NNRTI mutations found among these patients, and only 3 patients (7.5%) had these drug-resistant mutations. Clade typing and phylogenetic tree analysis showed HIV-1 subtype C predominance in these patients. Conclusions: Our study showed that higher percentage of HIV drug resistance mutations was found among HIV+TB+ individuals compared with tuberculosis-uninfected patients. Tuberculosis coinfection may be a risk factor for emergence of high frequency of drug resistance mutations. Studies with a larger sample size will help to confirm these findings from the Indian population.

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Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa

10.21203/rs.3.rs-32105/v1 ◽

2020 ◽

Author(s):

Adetayo Emmanuel Obasa ◽

Anoop T Ambikan ◽

Soham Gupta ◽

Ujjwal Neogi ◽

Graeme Brendon Jacobs

Keyword(s):

South Africa ◽

Drug Resistance ◽

Reverse Transcriptase ◽

Second Line ◽

Viral Quasispecies ◽

Resistance Mutations ◽

Reverse Transcriptase Inhibitors ◽

Nucleoside Reverse Transcriptase Inhibitors ◽

Drug Resistance Mutations ◽

Hiv 1

Abstract Background: HIV-1C has been shown to have a greater risk of virological failure and reduced susceptibility towards boosted protease inhibitors (bPIs), a component of second-line combination antiretroviral therapy (cART) in South Africa. This study entailed an evaluation of HIV-1 drug resistance-associated mutations (RAMs) among minor viral populations through high-throughput sequencing genotypic resistance testing (HTS-GRT) in patients suspected of failing on the South African national second-line cART regimen with bPIs.Methods: During 2017 and 2018, 67 patient samples were selected, of which 56 samples were successfully analyzed. All patients were receiving bPIs as part of their cART. Viral RNA was extracted, and complete pol genes were amplified and sequenced using Illumina HiSeq2500, followed by bioinformatics analysis to quantify the RAMs according to the Stanford HIV Drug Resistance Database.Results: Statistically significantly (p<0.001) higher PI RAMs were observed in minor viral quasispecies (25%; 14/56) compared to nucleoside reverse transcriptase inhibitors (11%; 6/56), non-nucleoside reverse transcriptase inhibitors (9%; 5/56) and integrase inhibitor RAM (4%; 2/56). The majority of the drug resistance mutations in the minor viral quasispecies were observed in the V82A mutation (n=13) in protease and K65R (n=5), K103N (n=7) and M184V (n=5) in reverse transcriptase.Conclusions: HTS-GRT improved the identification of PI and reverse transcriptase inhibitor (RTI) RAMs in second-line cART patients from South Africa compared to the conventional GRT with ≥20% used in Sanger-based sequencing. Several RTI RAMs, such as K65R, M184V or K103N and PI RAM V82A, were identified in <20% of the population. Deep sequencing could be of greater value in detecting acquired resistance mutations early.

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HIV-1 drug resistance mutations in children after failure of first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy

HIV Medicine ◽

10.1111/j.1468-1293.2010.00828.x ◽

2010 ◽

Vol 11 (9) ◽

pp. 565-572 ◽

Cited By ~ 19

Author(s):

T Puthanakit ◽

G Jourdain ◽

S Hongsiriwon ◽

P Suntarattiwong ◽

K Chokephaibulkit ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Transcriptase Inhibitor ◽

Resistance Mutations ◽

First Line ◽

Drug Resistance Mutations ◽

Nonnucleoside Reverse Transcriptase Inhibitor ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1

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Barcoding analysis of HIV drug resistance mutations using Oxford Nanopore MinION (ONT) sequencing

10.1101/240077 ◽

2017 ◽

Cited By ~ 2

Author(s):

Claudia Gonzalez ◽

Jessica Gondola ◽

Alma Y Ortiz ◽

Juan M Castillo ◽

Juan M Pascale ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Treatment Resistance ◽

Resistance Mutations ◽

Reverse Transcriptase Inhibitors ◽

Nucleoside Reverse Transcriptase Inhibitors ◽

Hiv Drug Resistance ◽

Drug Resistance Mutations ◽

Oxford Nanopore ◽

Pre Treatment

ABSTRACTDetermination of HIV drug resistance (HIVDR) is becoming an integral baseline HIV evaluation for newly infected subjects, as the level of pre-treatment resistance is increasing worldwide. Until now, the gold standard for monitoring ART mutations is the Sanger sequencing method, however, next-generation sequencing technologies (NGS) because high-throughput capability, are gaining attention as a method for detection of HIVDR. In the present work, we evaluated the use of the Oxford Nanopore Technologies (ONT) MinION as an alternative method for detection of drug resistance mutations in pre-treatment HIV positive subjects.We evaluate 36 samples taken during November 2016 from treatment naïve subjects with age greater than 18 years old, who went to the lab for their first HIV monitoring. To evaluate the agreement between Sanger and MinION generated sequences, we aligned the sequences (∼1200bp) with muscle v. 3.8.31. Then we counted the differences and calculated the p-distance of the obtained sequences, comparing paired sequences and grouping Sanger and MinION obtained sequences. The percentage of similarity among each sequence was also evaluated.All samples were submitted to the Standford University HIV drug resistance database (HIVdb version 8.4). Then we compared the resistance predictions obtained from the sequences generated by Sanger and MinION methods.Results: The median of available pores was 1314 for the first run, 1215 for the second run, and 536 for the third run. After 3 hours with SQK-NSK007 a total of 18803 2D reads were base-called and in 16577 reads (88%) a barcode was detected.Comparing the nucleotide differences of each sample, we observed that 23 (74%) samples had identical sequence, for the other samples the percentage of identity among each analyzed sequence was greater than 95%. A good positive predictive value (100%) in the estimation of drug resistance mutations in the groups of protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs).We present an approach for the analysis of HIV reads generated with MinION ONT, further studies are guaranteed before the application of this methodology in clinical settings to assess its suitability for HIVDR testing.

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Evaluation of a novel in-house HIV-1 genotype drug resistance assay using clinical samples in China

Current HIV Research ◽

10.2174/1570162x19666210910144433 ◽

2021 ◽

Vol 19 ◽

Author(s):

Peijie Gao ◽

Fengting Yu ◽

Xiaozhen Yang ◽

Dan Li ◽

Yalun Shi ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

High Efficiency ◽

Clinical Samples ◽

Genotype Distribution ◽

Resistance Mutations ◽

Reverse Transcriptase Inhibitors ◽

Nucleoside Reverse Transcriptase Inhibitors ◽

Subtype B ◽

Hiv 1

Background: HIV drug resistance poses a major challenge for anti-retroviral treatment (ART) and the prevention and control of HIV epidemic. Objective: The study aims to establish a novel in-house assay with high efficiency, named AP in-house method, that would be suitable for HIV-1 drug resistance detection in China. Methods: An in-house HIV-1 genotyping method was used to sequence the partial pol gene from 60 clinical plasma samples; the results of our test were compared with a commercial ViroSeq HIV-1 genotyping system. Results : Among sixty samples, 58(96.7%) were successfully amplified by AP in-house method, five of them harbored viral load below 1,000 copies/ml. The genotype distribution was 43.1% CRF07_BC (25/58), 39.7% CRF01_AE (23/58), 6.9% CRF55_01B (4/58), 5.2% subtype B (3/58) and 5.2% CRF08_BC (3/58). Compared with that of the ViroSeq system, the consistent rate of these nucleotides and amino acids obtained by AP in-house method was up to 99.5 ± 0.4% and 99.5 ± 0.4%, respectively. A total of 290 HIV-1 drug resistance mutations were identified by two methods, including 126 nucleoside reverse transcriptase inhibitors (NRTIs), 145 non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 19 protease inhibitors (PIs) resistance mutations. Out of them, 94.1% (273/290) were completely concordant between the AP in-house method and the ViroSeq system. Conclusion: Overall, the evaluation of AP in-house method provided comparable results to those of the ViroSeq system on diversiﬁed HIV-1 subtypes in China.

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

Virology Journal ◽

10.1186/s12985-021-01653-6 ◽

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.

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

Epidemiology and Infection ◽

10.1017/s0950268817003016 ◽

2018 ◽

Vol 146 (3) ◽

pp. 339-344 ◽

Cited By ~ 7

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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High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil

BioMed Research International ◽

10.1155/2021/5567332 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Yury Oliveira Chaves ◽

Flávio Ribeiro Pereira ◽

Rebeca de Souza Pinheiro ◽

Diego Rafael Lima Batista ◽

Antônio Alcirley da Silva Balieiro ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Protease Inhibitors ◽

People Living With Hiv ◽

Resistance Mutations ◽

Hiv Drug Resistance ◽

Drug Resistance Mutations ◽

Combined Antiretroviral Therapy ◽

Hiv 1

Virologic failure may occur because of poor treatment adherence and/or viral drug resistance mutations (DRM). In Brazil, the northern region exhibits the worst epidemiological scenarios for the human immunodeficiency virus (HIV). Thus, this study is aimed at investigating the genetic diversity of HIV-1 and DRM in Manaus. The cross-sectional study included people living with HIV on combined antiretroviral therapy and who had experienced virological failure during 2018-2019. Sequencing of the protease/reverse transcriptase (PR/RT) and C2V3 of the viral envelope gp120 (Env) regions was analyzed to determine subtypes/variants of HIV-1, DRMs, and tropism. Ninety-two individuals were analyzed in the study. Approximately 72% of them were male and 74% self-declared as heterosexual. Phylogenetic inference (PR/RT-Env) showed that most sequences were B subtype, followed by BF1 or B C mosaic genomes and few F1 and C sequences. Among the variants of subtype B at PR/RT, 84.3% were pandemic ( B PAN ), and 15.7% were Caribbean ( B CAR ). The DRMs most frequent were M184I/V (82.9%) for nucleoside reverse transcriptase inhibitors (NRTI), K103N/S (63.4%) for nonnucleoside reverse transcriptase inhibitor (NNRTI), and V82A/L/M (7.3%) for protease inhibitors (PI). DRM analysis depicted high levels of resistance for lamivudine and efavirenz in over 82.9% of individuals; although, low (7.7%) cross-resistance to etravirine was observed. A low level of resistance to protease inhibitors was found and included patients that take atazanavir/ritonavir (16.6%) and lopinavir (11.1%), which confirms that these antiretrovirals can be used—for most individuals. The thymidine analog mutations-2 (TAM-2) resistance pathway was higher in B CAR than in B PAN . Similar results from other Brazilian studies regarding HIV drug resistance were observed; however, we underscore a need for additional studies regarding subtype B CAR variants. Molecular epidemiology studies are an important tool for monitoring the prevalence of HIV drug resistance and can influence the public health policies.

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Drug Resistance Mutations to Protease and Reverse Transcriptase Inhibitors in Treatment Naive HIV-1 Clade C Infected Individuals from Mumbai, India

International Journal of Virology ◽

10.3923/ijv.2011.13.23 ◽

2010 ◽

Vol 7 (1) ◽

pp. 13-23 ◽

Cited By ~ 2

Author(s):

P.D. Potdar ◽

B.S. Daswani ◽

N.J. Rane

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Resistance Mutations ◽

Reverse Transcriptase Inhibitors ◽

Drug Resistance Mutations ◽

Clade C ◽

Treatment Naïve ◽

Hiv 1

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Prevalence of Transmitted HIV-1 Drug Resistance Among Treatment-naive Individuals in China, 2000-2016

10.21203/rs.3.rs-249916/v1 ◽

2021 ◽

Author(s):

Huangbo Yuan ◽

Zhenqiu Liu ◽

Xuefu Wu ◽

Mingshan Wu ◽

Qiwen Fang ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Genetic Relationships ◽

Transmitted Drug Resistance ◽

Resistance Mutations ◽

Reverse Transcriptase Inhibitors ◽

Nucleoside Reverse Transcriptase Inhibitors ◽

Relative Transmission ◽

Treatment Naïve ◽

Hiv 1

Abstract HIV with transmitted drug-resistance (TDR) limits the therapeutic options available for treatment-naive HIV patients. This study aimed to further our understanding of the prevalence and transmission characteristics of HIV with TDR for the application of first-line antiretroviral regimens. A total of 6578 HIV-1 protease/reverse-transcriptase sequences from treatment-naive individuals in China between 2000 and 2016, were obtained from the Los Alamos HIV Sequence Database and were analyzed for TDR. Transmission networks were constructed to determine genetic relationships. The spreading routes of large TDR clusters were identified using a Bayesian phylogeographic framework. TDR mutations were detected in 274 (4.51%) individuals, with 1.40% harboring TDR to nucleoside reverse transcriptase inhibitors, 1.52% to non-nucleoside reverse transcriptase inhibitors, and 1.87% to protease inhibitors. The most frequent mutation was M46L (58, 0.89%), followed by K103N (36, 0.55%), M46I (36, 0.55%), and M184V (26, 0.40%). The prevalence of total TDR initially decreased between 2000 and 2010 (OR = 0.83, 95% CI 0.73–0.95), and then increased thereafter (OR = 1.50, 95% CI 1.13–1.97). The proportion of sequences in a cluster (clustering rate) among HIV with TDR sequences was lower than that of sequences without TDR (40.5% vs. 48.8%, P = 0.023) and increased from 27.3% in 2005–2006 to 63.6% in 2015–2016 (P < 0.001). While most TDR mutations were associated with reduced relative transmission fitness, mutation M46I was associated with higher relative transmission fitness than the wild-type strain. This study identified a low-level prevalence of TDR HIV in China during the last two decades. However, the increasing TDR HIV rate sicn 2010, the persistent circulation of drug resistance mutations, and the expansion of self-sustaining drug resistance reservoirs may compromise the efficacy of antiretroviral therapy programs.

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